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.

The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids

PubMed Central

Contri, Renata V; Frank, Luiza A; Kaiser, Moacir; Pohlmann, Adriana R; Guterres, Silvia S

2014-01-01

Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main capsaicinoids (capsaicin and dihydrocapsaicin) on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC) was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP) did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution [CH-ET-CP]) and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% [CH-ET-CP] and 23% [commercial product]) and severe (8% [CH-ET-CP] and 69% [commercial product]) irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation. PMID:24611011

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.

Correlation between pH and irritant effect of cleansers marketed for dry skin.

PubMed

Baranda, Lourdes; González-Amaro, Roberto; Torres-Alvarez, Bertha; Alvarez, Carmen; Ramírez, Victoria

2002-08-01

Although it is important that dermatologists and the general population know the irritation potential of products marketed for dry skin used for body cleansing, this information is not usually available. To assess the irritative effect of different soaps and liquid cleansers recommended for sensitive skin. To study the correlation of the irritation effect of each substance with its pH and with the presence or absence of syndet in the product. Seventeen products marketed for dry skin and 12 common soaps used by the general population were studied. Fresh soap emulsions (8%) were applied to the volar side of the right forearm of 30 individuals with sensitive skin for 5 consecutive days using aluminum chambers. The appearance of irritation (erythema, scaling and fissures) was recorded, scored, and expressed in an Irritation index (IrIn). The pH of each solution was measured. Products with a low IrIn were White Dove (Dove, Lever Pond's, Toronto, Ontario, Canada), Dove Baby, Cetaphil (bar) (Cetaphil, Gulderma Lab., Forth Worth, TX, USA), Dove liquid cleanser for hands, Dove pink, and Aderma (Adenma, Pierre Fabre, Dermo-Cosmetique, Boulagne, France). Most corresponded to syndet products. Among the most used brand-name soap, Camay Classic (Camay, Procter & Gamble de Mexico, México, U.F.) had the lowest IrIn. Dove Baby was the only product with a neutral pH. A significant correlation between pH and the IrIn of cleansers was found (P < 0.006). Most products recommended for sensitive skin have a considerable irritation effect, which is related to the pH of the product. Better regulation of advertisement specifications including the pH level and type of cleanser contained is necessary for the majority of soaps and cleansers.

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.

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

PubMed

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

2017-10-01

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

In vivo skin penetration of macromolecules in irritant contact dermatitis.

PubMed

Abdel-Mottaleb, Mona M A; Lamprecht, Alf

2016-12-30

Recently, a selective preferential accumulation of polymeric nanoparticles (in the size range around 100nm) has been observed in the follicular system of dermatitis skin. The present investigation aimed at clearly investigating the effect of irritant contact dermatitis on the barrier permeability for colloidal systems below this size range, namely quantum dots and hydrophilic macromolecules. Irritant dermatitis was induced in mice and the penetrability of quantum dots (5nm) and hydrophilic dextran molecules has been tracked in both healthy and inflamed skin using confocal laser scanning microscopy. The selective accumulation of the quantum dots was clearly observed in inflamed skin while hydrophilic dextran behaved similarly in both healthy and inflamed skin. The therapeutic potential for the transdermal delivery of peptide drugs through inflamed skin has been also tested in rats. Results revealed that the transdermal permeation of insulin and calcitonin was not significantly enhanced in dermatitis compared to healthy skin. On the other side, permeation through stripped skin was significantly higher. However, the effect was limited and shorter compared to the SC injection where t min was 0.5h and 2h with a 70% and 46% reduction in blood glucose levels for the stripped skin and the SC injection respectively. Similarly, t min was 4h and 8h with area under the curve of 161±65% and 350±97% for the stripped skin and the SC injection respectively. In conclusion, the changes in skin permeability accompanied with skin inflammation did not affect its permeability to peptide drugs. Our findings also underline that experiments with the tape stripped skin model as a surrogate for inflamed skin can risk misleading conclusions due to significant difference of skin permeability between the tape stripped skin and inflamed skin. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Toxicity evaluation of the photoprotective compound LQFM048: Eye irritation, skin toxicity and genotoxic endpoints.

PubMed

de Ávila, Renato Ivan; de Sousa Vieira, Marcelo; Gaeti, Marilisa Pedroso Nogueira; Moreira, Larissa Cleres; de Brito Rodrigues, Laís; de Oliveira, Gisele Augusto Rodrigues; Batista, Aline Carvalho; Vinhal, Daniela Cristina; Menegatti, Ricardo; Valadares, Marize Campos

2017-02-01

A new molecule, LQFM048, originally designed through molecular hybridization using green chemistry approach, is in development as a photoprotective agent. Eye irritation, skin toxicity and genotoxicity evaluations are mandatory for predicting health risks. In this context, the purpose of this study was to investigate the eye irritation potential of LQFM048 by combining Short Time Exposure (STE), Bovine Corneal Opacity and Permeability (BCOP) associated with corneal histomorphometry and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Additionally, skin toxicity was evaluated by interleukin-18 production in the HaCaT keratinocyte, Local Lymph Node Assay (LLNA:BrdU-ELISA) method, 3T3 Neutral red uptake (NRU) assay and in vivo phototoxicity test. Genotoxic potential of LQFM048 was also analyzed by cytokinesis-block micronucleus assay (MNvit test-cytoB) in HepG2 cells. Our results showed that LQFM048 did not induce eye irritation and it was classified as UN GHS No Category for both STE and BCOP assays and non-irritating for HET-CAM test. LQFM048 showed non-potential skin sensitization with stimulation index (SI=0.7) in the LLNA:BrdU-ELISA method. Corroborating in vivo tests, it did not promote significant cytotoxicity in HaCaT cells and it showed similar levels of IL-18 when compared to control. Furthermore, LQFM048 induced non-phototoxic potential with photo-irritation factor (PIF) and mean photo effect (MPE) of 1 and -0.138, respectively, for 3T3 cells. Similarly, it was not phototoxic for in vivo testing with or without exposure to UVA, showing SI values of 1 and 1.2, respectively. The micronucleus test showed that LQFM048 was not genotoxic, under the conditions tested.In conclusion, LQFM048, a heterocyclic compound obtained through an environmentally acceptable simple synthetic route, seems to be safe for human use, especially for the development of a new sunscreen product, since it is neither an eye irritant, nor a contact allergen, nor mutagenic and nor

A study of the relationship between susceptibility to skin stinging and skin irritation.

PubMed

Basketter, D A; Griffiths, H A

1993-10-01

In an evaluation of the safety of new chemicals, of products containing them, or of novel formulations of existing chemicals which may come into contact with the skin, it is important to incorporate an assessment of specially susceptible sub-populations. Such a group is represented by those who are more likely to experience sensory effects such as stinging. Since these individuals are easily and rapidly identifiable, we investigated whether they represented a group who were also more susceptible to the effects of an irritant. The primary purpose was to discover whether 'stingers' might represent an easily and rapidly identifiable sub-population with a more generally increased tendency to give skin responses. The response to a 0.3% sodium dodecyl sulphate patch test was assessed in a group of 25 'stingers' and compared to the response in 25 'non-stingers'. There was no difference in either the pattern or strength of the irritant response assessed by subjective erythema and dryness scores. Thus the data suggest that there is no correlation between the susceptibility of an individual to a skin stinging response and an irritation reaction.

Proposal of limit concentrations for skin irritation within the context of a new EEC directive on the classification and labeling of preparations

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

Jacobs, G.; Martens, M.; Mosselmans, G.

1987-12-01

In this study, solvents belonging to different chemical families were tested for their irritating properties to the skin. The irritating potential of a chemical is expressed as its concentration in a nonirritant diluent beyond which irritation of the skin may be expected in the sense of EEC Directive 79/831/EEC. The substances were applied onto the shaved skin of rabbits by means of a modified Finn chamber for 4 hr. Afterward the exposure chamber was removed and the skin cleaned. Reading of erythema and edema was performed according to the scale of Draize at 1, 24, 48, and 72 hr aftermore » the removal of the patch. On the basis of the readings obtained the different dilutions of the organic solvents tested were classified as irritant or not according to the interpretation rules laid down in EEC Directive 83/467/EEC. On the basis of the structure-activity relationships found within each chemical family the irritation potential of the other members of the family could be derived via interpolation.« less

NEUROPEPTIDE MODULATION OF CHEMICALLY INDUCED SKIN IRRITATION

EPA Science Inventory

This study was designed to demonstrate that the early symptoms of chemically-induced skin irritation are neurally mediated. everal approaches were used to affect nerve transmission in adult Balb/c female mice. hese included general anesthesia (i.e., sodium pentobarbital), systemi...

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

PubMed

De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja

2006-06-01

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

The skin sensitization potential of four alkylalkanolamines.

PubMed

Leung, H W; Blaszcak, D L

1998-04-01

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

Evaluation of the skin irritation using a DNA microarray on a reconstructed human epidermal model.

PubMed

Niwa, Makoto; Nagai, Kanji; Oike, Hideaki; Kobori, Masuko

2009-02-01

To avoid the need to use animals to test the skin irritancy potential of chemicals and cosmetics, it is important to establish an in vitro method based on the reconstructed human epidermal model. To evaluate skin irritancy efficiently and sensitively, we determined the gene expression induced by a topically-applied mild irritant sodium dodecyl sulfate (SDS) in a reconstructed human epidermal model LabCyte EPI-MODEL (LabCyte) using a DNA microarray carrying genes that were related to inflammation, immunity, stress and housekeeping. The expression and secretion of IL-1alpha in reconstructed human epidermal culture is known to be induced by irritation. We detected the induction of IL-1alpha expression and its secretion into the cell culture medium by treatment with 0.075% SDS for 18 h in LabCyte culture using DNA microarray, quantitative reverse-transcription polymerase chain reaction (RT-PCR) and ELISA. DNA microarray analysis indicated that the expression of 10 of the 205 genes carried on the DNA microarray was significantly induced in a LabCyte culture by 0.05% or 0.075% SDS irritation for 18 h. RT-PCR analysis confirmed that SDS treatment significantly induced the expressions of interleukin-1 receptor antagonist (IL-1RN), FOS-like antigen 1 (FOSL1), heat shock 70 kDa protein 1A (HSPA1) and myeloid differentiation primary response gene (88) (MYD88), as well as the known marker genes for irritation IL-1beta and IL-8 in a LabCyte culture. Our results showed that a DNA microarray is a useful tool for efficiently evaluating mild skin irritation using a reconstructed human epidermal model.

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

PubMed

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

2005-11-01

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

Alp Rose stem cells, olive oil squalene and a natural alkyl polyglucoside emulsifier: Are they appropriate ingredients of skin moisturizers - in vivo efficacy on normal and sodium lauryl sulfate - irritated skin?.

PubMed

Filipović, Mila; Gledović, Ana; Lukić, Milica; Tasić-Kostov, Marija; Isailović, Tanja; Pantelić, Ivana; Vuleta, Gordana; Savić, Snežana

2016-11-01

Since skin moisturization may be achieved by both actives and chosen carrier, plant stem cells, squalene and natural alkyl polyglucoside emulsifier may be potential components of contemporary cosmetic products. The aim of the study was in vivo evaluation of the skin irritation potential and the efficacy of Alpine Rose stem cells incorporated into li-posomes and olive oil squalene as ingredients of moisturizing creams, with respect to the novel emulsifier used for creams’ stabilization. With the employment of noninvasive skin biophysical measurements, skin hydration (EC), transepi-dermal water loss (TEWL), erythema index (EI) and viscoelas-ticity were measured on 76 healthy volunteers. In the first phase, skin irritation after a 24-hour occlusion and the long-term efficacy of creams (a 21-day study) on healthy skin were evaluated. Phase II of the study focused on the cream efficacy assessment after a 6-day treatment of sodium lauryl sulfate-irritated skin. After a 24-hour occlusion, there were no significant changes in the EI for any tested sample. In the second phase of the study, the EI was not significantly altered for the cream containing squalene, while the application of all active samples resulted in a significant reduction of TEWL. In both phases of the study an EC increase was recorded, espe-cially for the squalene-containing cream. Due to the lack of skin irritation and skin barrier impairment along with the marked hydration effect, it could be said that the in-vestigated actives incorporated into alkyl polyglucoside emulsi-fier-stabilized creams may be safely applied as ingredients for "tailor-made" cosmetic moisturizers intended for normal and dry skin care, whereas olive oil squalene could be used for the treatment of irritated or sensitive skin as well. [Projekat Ministarstva nauke Republike Srbije, br. TR34031

Effect of Skin Protection and Skin Irritation on the Internal Exposure to Carbon Disulfide in Employees of the Viscose Industry.

PubMed

Kilo, Sonja; Zonnur, Nina; Uter, Wolfgang; Göen, Thomas; Drexler, Hans

2015-10-01

Occupational exposure to carbon disulfide (CS2) leads to inhalative and dermal uptake and thereby to internal exposure. In order to prevent occupational contact dermatitis, gloves and skin protection creams are used at the workplace. The aim of the study was the evaluation of the influence of personal skin protection and irritation on the internal exposure to CS2 of employees in the viscose industry. One hundred and eighty-two male CS2-exposed employees were included in the study and were examined regarding working conditions, use of personal protective measures und skin status. Personal air monitoring and biological monitoring was performed and the 'relative internal exposure' (RIE, internal exposure in relation to external exposure) calculated. A multiple regression analysis calculated the influence of skin protection and irritation on CS2 uptake. Usage of skin protection creams and gloves (and both in combination) while working was associated with a significantly higher RIE indicating a higher dermal penetration of CS2. Equally, irritated skin and younger age was associated with a higher internal burden. Gloves and skin protection creams are useful for preventing occupational skin diseases. However, when handling skin-resorptive substances like CS2, they can increase internal exposure or skin irritation. Therefore, we recommend the careful consideration of benefits and risks of protective creams and gloves at the workplace. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Evaluation of modifications of the traditional patch test in assessing the chemical irritation potential of feminine hygiene products.

PubMed

Farage, Miranda A; Meyer, Sandy; Walter, Dave

2004-05-01

product or a particular protocol variation. However, the mean irritation scores at those sites where a sensory effect was reported were higher than the mean irritation scores at those sites were no sensory effects were reported. All four protocol variations of the standard upper arm patch test can be used to assess the inherent chemical irritant properties of feminine protection products. For these products, which are inherently non-irritating, tape stripping and/or applying wet samples does not increase the sensitivity of the patch test method. Differences in irritation potential were apparent after one to three 24-h applications. Therefore, the standard patch test protocol can be shortened to three applications without compromising our ability to detect differences in the chemical irritation produced by the test materials. The patch test can be used to evaluate effectively the inherent chemical irritation potential of these types of products. However, this method is not suitable for testing the mechanical irritation due to friction that occurs during product use. There is no relationship between specific test conditions, i.e., compromised skin and/or testing wet samples and reports of perceived sensory reactions. However, there seems to be a clear relationship between sensory reactions and objective irritation scores.

Ethnic differences in objective and subjective skin irritation response: an international study.

PubMed

Lee, E; Kim, S; Lee, J; Cho, S-A; Shin, K

2014-08-01

Due to global marketing in the cosmetics industry, it is important to assess ethnic population susceptibility when evaluating the safety of cosmetic products or chemicals. To investigate ethnic variations in skin irritation response to positive irritants. Clinical testing was performed in four countries on two ethnic groups - Asian and Caucasian. We performed patch tests on the subjects' back with 0.5% aqueous sodium lauryl sulfate (SLS) and 0.15% retinol prepared in 1,3-butylene glycol. Stinging tests were performed using 5% aqueous lactic acid and 0.001% (w/v) capsaicin prepared in 10% ethanol solution separately. The incidence of self-perceived skin sensitivity was similar in the two ethnic groups. However, the incidence of adverse skin reaction to cosmetics appeared significantly higher in Asian (33.0%) than in Caucasian subjects (11.3%). For standard positive irritants such as 0.5% aqueous SLS solution, Asian subjects showed significantly higher scores than Caucasian subjects. The incidence of positive reaction to the 0.15% retinol patch test tended to be higher in Asian than in Caucasian subjects. Our data also showed that neurosensitivity to 5% lactic acid and 0.001% capsaicin was higher in Asian than in Caucasian subjects. Although self-reported skin sensitivity does not appear to differ according to ethnicity, there are ethnic differences in objective and subjective skin irritation responses to several standard positive materials. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dicationic Alkylammonium Bromide Gemini Surfactants. Membrane Perturbation and Skin Irritation

PubMed Central

Almeida, João A. S.; Faneca, Henrique; Carvalho, Rui A.; Marques, Eduardo F.; Pais, Alberto A. C. C.

2011-01-01

Dicationic alkylammonium bromide gemini surfactants represent a class of amphiphiles potentially effective as skin permeation enhancers. However, only a limited number of studies has been dedicated to the evaluation of the respective cytotoxicity, and none directed to skin irritation endpoints. Supported on a cell viability study, the cytotoxicity of gemini surfactants of variable tail and spacer length was assessed. For this purpose, keratinocyte cells from human skin (NCTC 2544 cell line), frequently used as a model for skin irritation, were employed. The impact of the different gemini surfactants on the permeability and morphology of model vesicles was additionally investigated by measuring the leakage of calcein fluorescent dye and analyzing the NMR spectra of 31P, respectively. Detail on the interaction of gemini molecules with model membranes was also provided by a systematic differential scanning calorimetry (DSC) and molecular dynamics (MD) simulation. An irreversible impact on the viability of the NCTC 2544 cell line was observed for gemini concentrations higher than 25 mM, while no cytotoxicity was found for any of the surfactants in a concentration range up to 10 mM. A higher cytotoxicity was also found for gemini surfactants presenting longer spacer and shorter tails. The same trend was obtained in the calorimetric and permeability studies, with the gemini of longest spacer promoting the highest degree of membrane destabilization. Additional structural and dynamical characterization of the various systems, obtained by 31P NMR and MD, provide some insight on the relationship between the architecture of gemini surfactants and the respective perturbation mechanism. PMID:22102870

[Development of alternative to animal experiment in evaluation of skin irritation caused by alcohol-based hand rubs].

PubMed

Yamamoto, Nobuyuki; Miyamoto, Koji; Katoh, Masakazu

2010-08-01

Alcohol-based hand rubs are widely used for infection control in clinical practice. However, it is known that frequent use of the alcohol-based hand rubs may cause skin irritation. To predict the skin irritation in human, animal experiments are quite useful. Especially, the Draize Test using rabbits is suitable for this purpose because their skin is highly sensitive. On the other hand, the development of alternative to animal experiments is important not only from the viewpoint of ethical aspects but also from the efficient research and development. Reconstructed human epidermis (RhE) was developed as a human skin equivalent model in vitro, and has been applied to the evaluation of skin irritation. But the RhE has not been utilized for the evaluation of alcohol-based hand rubs because of the high skin permeability and cytotoxicity of alcohols. The aim of this study was to develop a new method using the RhE in evaluation of skin irritation caused by alcohol-based hand rubs. The authors propose an experimental technique named "Skin model blowing method (SMBM)" consisting of the sequential procedure as follows; applying small amount of testing sample on RhE, blow-dry, post incubation, and cell viability measurement. According to the SMBM, the skin irritation caused by alcohol-based hand rubs could be evaluated under the similar condition of their actual use. It was found that a high correlation existed between the cell viability obtained from SMBM and the skin irritation index in rabbit which had been reported previously.

Cumulative irritation potential of topical retinoid formulations.

PubMed

Leyden, James J; Grossman, Rachel; Nighland, Marge

2008-08-01

Localized irritation can limit treatment success with topical retinoids such as tretinoin and adapalene. The factors that influence irritant reactions have been shown to include individual skin sensitivity, the particular retinoid and concentration used, and the vehicle formulation. To compare the cutaneous tolerability of tretinoin 0.04% microsphere gel (TMG) with that of adapalene 0.3% gel and a standard tretinoin 0.025% cream. The results of 2 randomized, investigator-blinded studies of 2 to 3 weeks' duration, which utilized a split-face method to compare cumulative irritation scores induced by topical retinoids in subjects with healthy skin, were combined. Study 1 compared TMG 0.04% with adapalene 0.3% gel over 2 weeks, while study 2 compared TMG 0.04% with tretinoin 0.025% cream over 3 weeks. In study 1, TMG 0.04% was associated with significantly lower cumulative scores for erythema, dryness, and burning/stinging than adapalene 0.3% gel. However, in study 2, there were no significant differences in cumulative irritation scores between TMG 0.04% and tretinoin 0.025% cream. Measurements of erythema by a chromameter showed no significant differences between the test formulations in either study. Cutaneous tolerance of TMG 0.04% on the face was superior to that of adapalene 0.3% gel and similar to that of a standard tretinoin cream containing a lower concentration of the drug (0.025%).

Experimental study on skin irritation of bone spur powder on rabbit

NASA Astrophysics Data System (ADS)

Ma, Zhenzhen; Zhang, Xuhui; Hao, Shaojun; Shen, Huiling; Wang, Huamin; Ji, Xianghui; Zhang, Zhengchen; Huang, Youling

2018-04-01

To observe the effect of bone powder of rabbit skin, provide the basis for the safety of clinical use of bone powder, 24 rabbits were randomly divided into 6 groups, complete skin test and damaged skin test each divided into 3 groups (n=4), high, low, 3 doses tested daily administered 1 times, continuous administration for 7 days, in 24 hours after the last administration of drug residues, wash with warm water, the removal of L hours after drug for 24 hours, 48 hours, 72 hours and seventh days, observed and recorded to apply position before administration and administration during the skin no erythema and edema, and observe the smear Parts of any pigmentation, bleeding, rough skin or thin skin etc., record the occurrence time and duration time. Through comparative observation, intact skin group before administration and dosing period, there were no erythema and edema, pigmentation, bleeding, rough skin or thin skin etc., there is no difference with the control group; the damaged skin group after administration of 1 to 5 days, each rabbit skin there are different degrees of erythema and edema, especially to skin injury after 24-48 hours is obvious, 2 days (48 hours) after 4 days gradually reduced, significantly subsided after 6 days, erythema and edema phenomenon subsided completely, not out of blood, pigmentation, rough skin or thin skin and so on. The bone spur powder has no irritation on the intact skin of rabbits. The bone spur powder has moderate irritation on the damaged skin of rabbits, but after 48 hours, the stimulation reaction subsided spontaneously, which is caused by the inflammatory reaction caused by skin injury, rather than the medication. The bone spur powder is safe for clinical use.

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.

[Changes of nitric oxide after trichloroethylene irritation in hairless mice skin and protection of ginkgo biloba extract and vitamin E].

PubMed

Wang, Liang; Shen, Tong; Zhou, Cheng-fan; Yu, Jun-feng; Zhu, Qi-xing

2009-04-01

To study the changes of nitric oxide (NO) in the BALB/c hairless mice skin after trichloroethylene (TCE) irritation and the protection of ginkgo biloba extract (GbE) and vitamin E (VE). 132 BALB/c hairless mice were randomly divided into blank control group, solvent group (olive oil), TCE groups (20%TCE, 40%TCE, 80%TCE and 100%TCE), GbE groups (0.1%GbE, 1%GbE and 10%GbE) and VE groups (5%VE, 10% VE and 20% VE), with 11 animals in each group, 5 for acute irritation test and 6 for the cumulative irritation test. The skin irritation was observed, and the levels of NO in the dorsal skin of BALB/C hairless mice were detected. The kit of NO was used to detect the levels of NO in the dorsal skin of BALB/c hairless mice. (1) The skin presented erythema and edema after TCE irritation both in acute irritation and cumulative irritation test and the skin inflammation showed time-dose effect relationship; the mice skin was protected in GbE or VE groups. (2) In the acute stimulation test, the levels of NO in 80%TCE group (69.895 +/- 9.605 micromol/mg pro) and 100%TCE group (77.273 +/- 9.290 micromol/mg pro) were significantly different compared with blank control group and solvent control group (P < 0.05 or P < 0.01). In the protection group, the NO level were reduced, with the statistically significant differences. (3) In acute irritation test, the levels of NO in 80%TCE group (60.362 +/- 9.817 micromol/mg pro) and 100%TCE group (68.027 +/- 9.354 micromol/mg pro) were significantly different compared with blank control group and solvent control group, (P < 0.05 or P < 0.01); In the protection group, 1% GbE, 10% GbE, 10% VE and 20%VE could reduce the levels of NO, with statistically significant differences. TCE can produce the irritation on the dorsal skin of BALB/c hairless mice and induce the significant increase of the NO levels. GbE and VE can protect the skin from TCE irritation damage.

Efficacy of dexpanthenol in skin protection against irritation: a double-blind, placebo-controlled study.

PubMed

Biro, Kathrin; Thaçi, Diamant; Ochsendorf, Falk R; Kaufmann, Roland; Boehncke, Wolf-Henning

2003-08-01

Dexpanthenol is popular in treating various dermatoses and in skin care, but few controlled clinical trials have been performed. We investigated the efficacy of dexpanthenol in skin protection against irritation in a randomized, prospective, double-blind, placebo-controlled study. 25 healthy volunteers (age 18-45 years) were treated for the inner aspect of both forearms with either Bepanthol Handbalsam containing 5% dexpanthenol or placebo x2 daily for 26 days. From day 15-22, sodium lauryl sulfate (SLS) 2% was applied to these areas x2 daily. Documentation comprised sebumetry, corneometry, pH value and clinical appearance (photographs). 21 volunteers completed the study, 3 were excluded because of non-compliance and 1 experienced a non-study-related, severe, adverse event. Only corneometry yielded a statistically significant difference, with decreased values following SLS challenge at the placebo sites (P < 0.05). Intraindividual comparisons showed superior results at the dexpanthenol-treated sites in 11 cases and in only 1 case at the placebo site. 6 volunteers experienced an irritant contact dermatitis, with more severe symptoms at the placebo site in 5 cases. In conclusion, dexpanthenol exhibits protective effects against skin irritation. The initiation of a study to evaluate the efficacy of dexpanthenol in preventing irritant occupational contact dermatitis under real workplace conditions is validated.

Genotoxicity, acute oral and dermal toxicity, eye and dermal irritation and corrosion and skin sensitisation evaluation of silver nanoparticles.

PubMed

Kim, Jin Sik; Song, Kyung Seuk; Sung, Jae Hyuck; Ryu, Hyun Ryol; Choi, Byung Gil; Cho, Hyun Sun; Lee, Jin Kyu; Yu, Il Je

2013-08-01

To clarify the health risks related to silver nanoparticles (Ag-NPs), we evaluated the genotoxicity, acute oral and dermal toxicity, eye irritation, dermal irritation and corrosion and skin sensitisation of commercially manufactured Ag-NPs according to the OECD test guidelines and GLP. The Ag-NPs were not found to induce genotoxicity in a bacterial reverse mutation test and chromosomal aberration test, although some cytotoxicity was observed. In acute oral and dermal toxicity tests using rats, none of the rats showed any abnormal signs or mortality at a dose level of ∼ 2000 mg/kg. Similarly, acute eye and dermal irritation and corrosion tests using rabbits revealed no significant clinical signs or mortality and no acute irritation or corrosion reaction for the eyes and skin. In a skin sensitisation test using guinea pigs, one animal (1/20) showed discrete or patchy erythema, thus Ag-NPs can be classified as a weak skin sensitiser.

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.

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.

Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium lauryl sulphate-induced irritation.

PubMed

Proksch, E; Nissen, H P

2002-12-01

Dexpanthenol-containing creams have been widely used for treatment of lesions (superficial wounds) of the skin and mucous membranes. Dexpanthenol is converted in tissues to pantothenic acid, a component of coenzyme A. Coenzyme A catalyses early steps in the synthesis of fatty acids and sphingolipids which are of crucial importance for stratum corneum lipid bilayers and cell membrane integrity. In the present study, the effects were examined of a dexpanthenol-containing cream on skin barrier repair, stratum corneum hydration, skin roughness, and inflammation after sodium lauryl sulphate (SLS)-induced irritation. Irritation was induced by application of SLS in patch test chambers. The dexpanthenol-contaming cream or the vehicle were applied twice daily and barrier repair, hydration, roughness, and inflammation of the skin were determined by using biophysical methods. Significantly accelerated skin barrier repair was found in treatments with the dexpanthenol-containing cream (verum) compared with vehicle-treated (placebo) or untreated skin. Both verum and placebo showed an increase in stratum corneum hydration, but significantly more so with the dexpanthenol-containing cream. Both creams reduced skin roughness, but again the verum was superior. The dexpanthenol-containing cream significantly reduced skin redness as a sign of inflammation in contrast to the vehicle, which produced no effect. Treatment with a dexpanthenol-containing cream showed significantly enhanced skin barrier repair and stratum corneum hydration, while reducing skin roughness and inflammation.

Oral administration of glucosylceramide ameliorates inflammatory dry-skin condition in chronic oxazolone-induced irritant contact dermatitis in the mouse ear.

PubMed

Yeom, Mijung; Kim, Sung-Hun; Lee, Bombi; Han, Jeong-Jun; Chung, Guk Hoon; Choi, Hee-Don; Lee, Hyejung; Hahm, Dae-Hyun

2012-08-01

Irritant contact dermatitis (ICD) is an inflammatory skin disease triggered by exposure to a chemical that is toxic or irritating to the skin. A major characteristic of chronic ICD is an inflammatory dry-skin condition with associated itching. Although glucosylceramide (GlcCer) is known to improve the skin barrier function, its mechanism of action is unknown. Using a mouse model of oxazolone-induced chronic ICD, this study investigated the effects of oral administration of GlcCer on inflammatory dry skin. Chronic ICD was induced by repeated application of oxazolone in mice. GlcCer was orally administered once daily throughout the elicitation phase. The beneficial efficacy of GlcCer on cutaneous inflammation was evaluated by assessing ear thickness, lymph node weight, histological findings, and mRNA expression of pro-inflammatory cytokines such as IL-1β and IL-6. Additionally, parameters of the itch-associated response, including scratching behavior, water content of the skin, and aquaporin-3 levels in the lesional ear, were measured. Oral GlcCer administration significantly suppressed mRNA expression of the pro-inflammatory cytokines IL-1β and IL-6. GlcCer also suppressed ear swelling, lymph node weight gains, and infiltration of leukocytes and mast cells in ICD mice. In oxazolone-induced ICD mice, GlcCer significantly inhibited irritant-related scratching behavior and dehydration of the stratum corneum, and decreased aquaporin-3 expression. Our results indicate that GlcCer suppressed inflammation not only by inhibiting cytokine production but also by repairing the skin barrier function, suggesting a potential beneficial role for GlcCer in the improvement of chronic ICD. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

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

Kosten, Ilona J.; Spiekstra, Sander W.; Gruijl, Tanja D. de

After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a{sup +} MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topicalmore » exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a{sup −}/CD14{sup +}/CD68{sup +} which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. - Highlights: • MUTZ-3 derived Langerhans cells integrated into skin equivalents are fully functional. • Anti-CXCL12 blocks allergen-induced MUTZ-LC migration

[Efficacy and patient benefit of treatment of irritated skin with ointments containing dexpanthenol: health services research (observational study) on self-medication in a pharmaceutical network].

PubMed

Radtke, M A; Lee-Seifert, C; Rustenbach, S J; Schäfer, I; Augustin, M

2009-05-01

Products containing dexpanthenol are used to treat irritated and inflamed skin. So far there is a lack of data for the evidence of patient-relevant benefits. Assessment of the patient-relevant benefit of ointments containing dexpanthenol in the self-medicated therapy of irritated skin. Prospective, observational study in a network of 392 pharmacies. Consecutive recruitment of n=1,886 patients with symptoms of irritated skin, including non-inflammatory intervals of atopic eczema, other xerotic skin conditions and impairment of skin barrier. The patient-relevant benefit was ascertained prior to and 7-10 days after treatment through the patient-benefit index (PBI). The PBI showed that 91.5% of the patients experienced a relevant benefit from treatment. 94.7% directly indicated to have had achieved successful therapeutic results. All symptoms of irritated skin (e.g. xerosis, erythema, desquamation) significantly improved (pskin disease. High patient-relevant benefits were observed in the treatment of irritated skin with dexpanthenol ointment.

Biopharmaceutical Assessment and Irritation Potential of Microemulsions and Conventional Systems Containing Oil from Syagrus cearensis for Topical Delivery of Amphotericin B Using Alternative Methods.

PubMed

Sousa, Giovana D; Kishishita, Juliana; Aquino, Kátia A S; Presgrave, Octávio A F; Leal, Leila B; Santana, Davi P

2017-07-01

The aim of this study was to compare the biopharmaceutical characteristics and irritation potentials of microemulsions (MEs) and conventional systems (CSs) containing oil from Syagrus cearensis for topical delivery of Amphotericin B (AmB). Pseudo-ternary phase diagrams were constructed using a water titration method to develop the MEs, and the CSs were prepared according to the classical technique of phase inversion. In the skin permeation and retention study, dermatomed pig skin without stratum corneum was used as an alternative disturbed skin model. The irritation potential was evaluated using three different methods, chorioallantoic membrane assays (HET-CAM and CAM-TBS), and bovine corneal opacity and permeability (BCOP) test. The optimized formulation (ME1) consisting of 0.1% (w/w) Amphotericin B, 9.1% (w/w) catolé oil, 81% (w/w) Smix (1:1, Tween 20 and Kolliphor EL) possessed droplet size of 31.02 ± 0.9 nm, zeta potential of -23.4 mV, and viscosity 0.63 ± 0.1 Pa.s. ME1 exhibited greater retention of AmB in to skin layers (84.79 ± 2.08 μg cm -2 ) than all the others formulations. In general, MEs showed higher drug release and retention than CSs and all of the formulations showed greater retentivity than permeability. Only MEs developed using Labrasol/Plurol Oleique (L/PO) as the surfactant and co-surfactant exhibited a moderate irritation potential; all other MEs and CSs were classified as non-irritants or slight irritants. The results indicate that formulations containing oil from S. cearensis are promising alternatives for the delivery of AmB targeting the treatment of cutaneous leishmaniasis.

Assessment of human epidermal model LabCyte EPI-MODEL for in vitro skin irritation testing according to European Centre for the Validation of Alternative Methods (ECVAM)-validated protocol.

PubMed

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

2009-06-01

A validation study of an in vitro skin irritation testing method using a reconstructed human skin model has been conducted by the European Centre for the Validation of Alternative Methods (ECVAM), and a protocol using EpiSkin (SkinEthic, France) has been approved. The structural and performance criteria of skin models for testing are defined in the ECVAM Performance Standards announced along with the approval. We have performed several evaluations of the new reconstructed human epidermal model LabCyte EPI-MODEL, and confirmed that it is applicable to skin irritation testing as defined in the ECVAM Performance Standards. We selected 19 materials (nine irritants and ten non-irritants) available in Japan as test chemicals among the 20 reference chemicals described in the ECVAM Performance Standard. A test chemical was applied to the surface of the LabCyte EPI-MODEL for 15 min, after which it was completely removed and the model then post-incubated for 42 hr. Cell v iability was measured by MTT assay and skin irritancy of the test chemical evaluated. In addition, interleukin-1 alpha (IL-1alpha) concentration in the culture supernatant after post-incubation was measured to provide a complementary evaluation of skin irritation. Evaluation of the 19 test chemicals resulted in 79% accuracy, 78% sensitivity and 80% specificity, confirming that the in vitro skin irritancy of the LabCyte EPI-MODEL correlates highly with in vivo skin irritation. These results suggest that LabCyte EPI-MODEL is applicable to the skin irritation testing protocol set out in the ECVAM Performance Standards.

Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment.

PubMed

Li, Chun-yu; Wang, Zhe-wei; Tu, Can; Wang, Jia-bo; Jiang, Bing-qian; Li, Qi; Zeng, Ling-na; Ma, Zhi-jie; Zhang, Ping; Zhao, Yan-ling; Zhang, Ya-ming; Yan, Dan; Tan, Rui; Xiao, Xiao-he

2014-10-01

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.

Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment*

PubMed Central

Li, Chun-yu; Wang, Zhe-wei; Tu, Can; Wang, Jia-bo; Jiang, Bing-qian; Li, Qi; Zeng, Ling-na; Ma, Zhi-jie; Zhang, Ping; Zhao, Yan-ling; Zhang, Ya-ming; Yan, Dan; Tan, Rui; Xiao, Xiao-he

2014-01-01

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs. PMID:25294378

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.

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

PubMed

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

2010-03-01

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

Use of in vitro methods to rank surfactants for irritation potential in support of new product development.

PubMed

Casterton, P L; Potts, L F; Klein, B D

1994-08-01

11 surfactant raw materials with potential applications in light-duty liquid cleaning products were evaluated in vitro using a human skin analogue (ATS SKIN(2) Model ZK1100) for predicting cytotoxicity (MTT reduction) and inflammation [prostaglandin E(2) (PGE(2)) release]. Two of the 11 raw materials, both in the same compound family, were selected to be individually combined with each of the other nine in a 90:10 (raw:selected raw) mixture. Selection criteria were based on desired performance characteristics and low irritation potential as suggested from the individual surfactant assay data. To determine whether irritation potential was mitigated, MTT and PGE(2) scores were again determined for each of the 18 combinations with the resulting data being compared with the untreated raw material data. A plot of the data indicated that one of two selected materials may have an 'anti-irritant' effect. For raw materials with intrinsic MTT scores of less than 50 mug/ml and with the original data corrected for possible dilution effects, a statistical comparison between individual raw materials and the two sets of combinations was done using a one-sample analysis. Both cytotoxicity (MTT) and inflammation (PGE(2)) were significantly decreased by the milder of the two selected raw materials. By factoring the data into future new product decisions, this methodology has become a useful and practical tool for Amway product development.

Mechanistic Analysis of Human Skin Distribution and Follicular Targeting of Adapalene-Loaded Biodegradable Nanospheres With an Insight Into Hydrogel Matrix Influence, In Vitro Skin Irritation, and In Vivo Tolerability.

PubMed

Sallam, Marwa Ahmed; Marín Boscá, María Teresa

2017-10-01

This work aimed at the development of a biocompatible, non-oily nanomedicine for follicular delivery of adapalene (AD) ameliorating its irritation potential for convenient localized topical treatment of acne vulgaris. AD was efficiently incorporated into poly-ε-caprolactone nanospheres (NS) with an encapsulation efficiency of 84.73% ± 1.52%, a particle size of 107.5 ± 8.19 nm, and zeta potential of -13.1 mV demonstrating a sustained-release behavior. The AD-NS were embedded in either hydroxypropyl methylcellulose (HPMC) or hyaluronate (HA) gel. The ex vivo human skin dermatokinetics of AD from each system was studied. The nanoparticles dispersion showed significantly higher AD retention in the epidermis and dermis than AD suspension. NS-HPMC decreased whereas NS-HA increased AD retained in all the skin layers. The fate of the NS and the role of the hydrogel in modulating skin distribution was evaluated by confocal laser scanning microscopy (CLSM) imaging of fluorescently labeled NS. CLSM illustrated follicular localization of the florescent NS. HPMC gel restricted the presence of NS to the stratum corneum and epidermis. HA gel enhanced the penetration of NS to all the skin layers. In vitro skin irritation using human dermal fibroblasts and in vivo animal tolerability studies were performed. Accordingly, HA gel-dispersed AD-NS presented a nonirritant compromised cosmeceutical formulation suitable for oily acneic skin. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Formulation of tretinoin-loaded topical proniosomes for treatment of acne: in-vitro characterization, skin irritation test and comparative clinical study.

PubMed

Rahman, Salwa Abdel; Abdelmalak, Nevine Shawky; Badawi, Alia; Elbayoumy, Tahany; Sabry, Nermeen; El Ramly, Amany

2015-01-01

Tretinoin (TRT) is a widely used retinoid for the topical treatment of acne, photo-aged skin, psoriasis and skin cancer which makes it a good candidate for topical formulation. Yet side effects, like redness, swelling, peeling, blistering and, erythema, in addition to its high lipophilicity make this challenging. Therefore, the aim of this study was the development of TRT-loaded proniosomes to improve the drug efficacy and to increase user acceptability and compliance by reducing its side effects. Nine formulae were prepared according to 3(2) factorial design and were evaluated for their morphology, vesicle size, entrapment efficiency (EE %), and% of drug released after 5 h. Hydrogel of the candidate formula, N8G (proniosomes prepared with 0.025% TRT, and Span60: cholesterol molar ratio of 3:1 and incorporated in 1% carbopol gel) was developed and evaluated for skin irritation test and clinical study in acne patients compared to marketed product. Candidate formula showed higher efficacy and very low irritation potential when compared to marketed product in human volunteers.

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

PubMed

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

2013-11-01

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

Ceramide 1 and ceramide 3 act synergistically on skin hydration and the transepidermal water loss of sodium lauryl sulfate-irritated skin.

PubMed

Huang, Huey-Chun; Chang, Tsong-Min

2008-08-01

Stratum corneum intercellular lipids, such as ceramides, play an important role in the regulation of skin water barrier homeostasis and water-holding capacity. Aim To evaluate the potential water retention capacity of control emulsion and three oil-in-water (o/w) emulsions containing ceramide 1, ceramide 3, or both. Fifteen healthy Asian women (age, 20-30 years) with healthy skin, pretreated with sodium lauryl sulfate (SLS), applied the tested emulsions twice daily over a period of 28 days. Skin hydration and transepidermal water loss (TEWL) values were measured on the indicated days with a Corneometer(R)825 and a TEWAMETER TM210, respectively. The maximum increase in skin humidity was reached after 4 weeks, with values of 21.9 +/- 1.8% and 8.9 +/- 0.9% for emulsion C and control emulsion, respectively. The maximum decrease in TEWL was also reached after 4 weeks, with values of 36.7 +/- 4.7% and 5.1 +/- 0.8% for the same emulsions. It can be concluded that all the tested ceramide-containing emulsions improved skin barrier function when compared with untreated skin. There was some indication that ceramides 1 and 3 contained in emulsion C might exert a beneficial synergistic effect on skin biochemical properties, such as skin hydration and TEWL, and play a key role in the protection mechanism against SLS irritation.

Evaluation of fibrin-based dermal-epidermal organotypic cultures for in vitro skin corrosion and irritation testing of chemicals according to OECD TG 431 and 439.

PubMed

Morales, Mariana; Pérez, David; Correa, Luis; Restrepo, Luz

2016-10-01

Reconstructed human epidermis (RhE) models have been used for in vitro testing of the potential harmful effects of exposure to chemical compounds on health. In the past, skin irritation and corrosion were evaluated in animal models; however, in recent years, due to the bioethics implications of the method and, to minimize the use of experimental animals, alternative procedures have been proposed. The Organisation for Economic Co-operation and Development (OECD) in its test guidelines (TG) 431 and 439 indicates the requirements for validating new methods for the evaluation of skin corrosion and irritation, respectively. Here, we present an in-house human dermal-epidermal model, useful for the performance of these tests. Using the methods described in this work, it was possible to obtain human fibrin-based dermal-epidermal organotypic skin cultures (ORGs) displaying similar histological characteristics to native skin and expressing specific differentiation epithelial proteins. The end points to classify a substance as irritant or corrosive were cell viability evaluated by MTT assay, and cytokine release measured by BD CBA for human inflammatory cytokines. According to the MTT test, the ORGs correctly classified irritating and corrosive substances. Moreover, the cytokine release assay was difficult to interpret in the context of testing chemical hazard classification. Further experiments are needed to validate this new model for the evaluation of surfactants because the fibrin matrix was affected in the presence of these substances. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficacy of a Hand Regimen in Skin Barrier Protection in Individuals With Occupational Irritant Contact Dermatitis.

PubMed

Jordan, Laura

2016-11-01

Occupational irritant contact dermatitis (OICD) is a dif cult and hard to manage condition. It occurs more frequently in certain occupations where contact with harsh chemicals, use of alcohol-based disinfectants, and frequent hand washing heightens the risk. Treatment for OICD includes patient education in addition to physical, topical, and systemic therapies. To review the pathogenesis and treatment options for OICD and evaluate the ef cacy of a selective skin-care regimen involv- ing a hand protectant cream alone as well as combined with a repair cream and speci c cleanser. A single-center open study was performed comprising 42 healthy male and female adult volunteers prone to occupational irritant contact dermatitis due to frequent wet work or contact with detergents. Between day 0 and day 7, subjects applied a hand protectant cream as needed on both hands (at least twice daily). On days 7 to 14, subjects applied a hand protectant cream and cleanser as needed on both hands (at least twice daily) as well as a repair cream each evening. A diary log was given to each volunteer for application control and for a subjective evaluation of daily tolerability. In these subjects prone to occupational irritant contact dermatitis, the hand protectant cream applied during the initial 7-day period was effective in restoring the damaged skin barrier and improving the stratum corneum hydration. A regimen that combined the hand protectant and repair creams with a speci c cleanser during a further 7-day period allowed contin- ued improvement of skin hydration and additional clinical bene ts while respecting the skin barrier function. The results of this study support the use of a 3-step approach for patients who are at risk of repeated exposure to external irritants. J Drugs Dermatol. 2016;15(suppl 11):s81-85..

Kinetic analysis on the skin disposition of cytotoxicity as an index of skin irritation produced by cetylpyridinium chloride: comparison of in vitro data using a three-dimensional cultured human skin model with in vivo results in hairless mice.

PubMed

Kano, Satoshi; Sugibayashi, Kenji

2006-02-01

The aim of this study was to kinetically and dynamically analyze in vitro cytotoxicity as an index of skin irritation by use of a three-dimensional cultured human skin model and to compare the in vitro assay data with data from living animals. A cationic surfactant, cetylpyridinium chloride (CPC), was selected as a model irritant. Living skin equivalent-high (LSE-high) and hairless mice were used for the in vitro and in vivo tests, respectively. Skin irritation dermatodynamics was evaluated by calorimetric thiazoyl blue (MTT) conversion assay both for in vitro and in vivo tests, whereas dermatokinetics of CPC in LSE-high and mouse skin were evaluated using HPLC. The time course of cell viability in the skin after application of CPC to intact skin was distinctly different from that of stratum-corneum-stripped skin in both LSE-high and hairless mice. Biphasic behavior characterized by two first-order rates with an inflection time point was observed in intact skin, whereas cell viability monoexponentially decreased immediately after CPC application in stripped skin. The time courses of cell viability in the skin and dermatodynamics were closely related to that of dermatokinetics of CPC. The present study demonstrates that the in vitro cytotoxic profile was similar to the in vivo cytotoxicity test and that dermatodynamics was related to dermatokinetics of CPC.

A controlled, three-part trial to investigate the barrier function and skin hydration properties of six skin protectants.

PubMed

Hoggarth, Andrew; Waring, Mike; Alexander, James; Greenwood, Amanada; Callaghan, Theresa

2005-12-01

In the treatment of incontinence dermatitis, a skin protectant primarily prevents skin breakdown due to moisture and biological irritants in urine and feces. To assess the barrier and skin hydration properties of six currently available skin protectants with different formulations, a controlled, three-phase study was conducted at a research facility in the UK among 18 healthy volunteers. The study addressed each product's efficacy against insult from a known irritant (sodium lauryl sulphate), skin hydration potential, and maintenance of skin barrier and barrier efficacy against maceration. Using white petrolatum (glycerin) as the positive control and untreated sites as the negative control, the results show that each one of the products tested has different performance properties. Products containing petrolatum demonstrated protection against irritants (P = 0.006 at 24 hours) and maceration (P < 0.005) and provided some skin hydration. Products containing dimethicone varied in protection against irritants (P < 0.005, or P > or = 0.806 at 24 hours) and have good skin hydration potential and low barrier efficacy (P > 0.500). Zinc oxide-based products showed protection against irritants (P < 0.005) but poor skin hydration and barrier properties to prevent maceration (P = 0.262). Overall, only the water-in-oil petrolatum- based product performed effectively within all the parameters tested. This study suggests that skin barrier protection involves more than the inclusion of an active barrier ingredient. Further testing and use of barrier products in the clinical setting will provide additional evidence for appropriate product selection.

A double-blind, randomized, bilateral comparison of skin irritancy following application of the combination acne products clindamycin/tretinoin and benzoyl peroxide/adapalene.

PubMed

Goreshi, Renato; Samrao, Aman; Ehst, Benjamin D

2012-12-01

The use of topical medications for acne vulgaris is often limited by their irritant properties. Newer combination preparations are available and offer convenience, but irritant potential may still be a hindrance, perhaps more so with the combination of 2 agents. Few studies have compared these formulations directly for tolerability. We sought to compare the tolerability of 2 combination topical acne products, clindamycin 1.2%-tretinoin 0.025% (CLIN/RA) gel and benzoyl peroxide 2.5%-adapalene 0.1% (BPO/ADA) gel. CLIN/RA and BPO/ADA were applied daily to opposite sides of a subject's face for 21 days in a double-blinded fashion. Investigators' Global Assessments and study subject self-assessments of burning/stinging, itching, erythema, and dryness/scaling were collected. Transepidermal water loss (TEWL) was also measured as an objective measure of skin irritation. A mixed model analysis and repeated-measures analysis of variance were used to compare outcomes for both acne formulations. CLIN/RA produced significantly less burning/stinging than BPO/ADA (P<.001) as well as significantly less pruritus than BPO/ ADA (P<.001). BPO/ADA caused significantly more TEWL than CLIN/RA (P=.005). There was no significant difference in the amount of erythema or the amount of dryness/scaling caused by either formulation. CLIN/RA produced significantly less skin irritancy and TEWL than BPO/ADA.

Acute toxicity and primary irritancy of alkylalkanolamines.

PubMed

Ballantyne, B; Leung, H W

1996-12-01

The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MEA), N, N, -dimethylethanolamine (DMEA), N, N, -dimethylisopropanolamine (DMIPA), N-methyldiethanolamine (MDEA), and tertbutyldiethanolamine (BDEA). All these alkylalkanolamines were of comparable acute peroral toxicity in the rat (LD50 range 1.48-2.83 ml/kg). By 24 h occluded epicutaneous contact in the rabbit, MEA, DMEA and DMIPA were of moderate acute percutaneous toxicity (LD50 range 1.13-2.0 ml/kg), MDEA was of slight acute percutaneous toxicity (LD50 male 9.85 ml/kg, female 10.90 ml/kg), and BDEA of intermediate toxicity (LD50 6.4 ml/kg). Due to differences in vapor pressure the acute vapor exposure toxicity of the alkylalkanolamines to rats varied; MEA, MDEA and BDEA were of a low order of acute toxicity, and DMIPA was moderately toxic with an LT50 of 3.2 h for a saturated vapor atmosphere exposure. A 4 h-LC50 (rat combined sex) of 1461 ppm was determined for DMEA. All alkylalkanolamines studied, except MDEA, were moderately to markedly irritating and caused variable degrees of skin corrosivity; MDEA caused only transient minor skin irritation. In accord with the skin irritancy results, the eye irritancy from 0.005 ml MEA, DMEA, DMIPA and BDEA was severe, and that from MDEA was slight. Exposure to these compounds has implications for occupational health procedures.

High molecular compounds (polysaccharides and proanthocyanidins) from Hamamelis virginiana bark: influence on human skin keratinocyte proliferation and differentiation and influence on irritated skin.

PubMed

Deters, A; Dauer, A; Schnetz, E; Fartasch, M; Hensel, A

2001-11-01

Although extracts from Hamamelis bark have long been used in therapy of skin diseases and in cosmetic formulas there are only few pharmacological investigations verifying the activity of distinct Hamamelis bark constituents. Therefore two major classes of constituents, namely polymeric proanthocyanidins and polysaccharides were isolated from Hamamelis bark and tested concerning their influence on proliferation and differentiation of cultured human keratinocytes. While the polysaccharide fraction, consisting mainly of arabans and arabinogalactans, did not effect human keratinozytes, the proanthocyanidins strongly increased the proliferation of the cells, while the differentiation was not influenced significantly. Within a preliminary cumulative in vivo study on SLS-irritated skin, proanthocyanidins (ProcyanoPlus) were proven to reduce transepidermal water loss and erythema formation. Furthermore, a clinical scoring indicated that procyanidins can influence irritative processes significantly.

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

PubMed Central

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

2011-01-01

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

In vivo assessment of cytological changes by means of reflectance confocal microscopy - demonstration of the effect of topical vitamin E on skin irritation caused by sodium lauryl sulfate.

PubMed

Casari, Alice; Farnetani, Francesca; De Pace, Barbara; Losi, Amanda; Pittet, Jean-Christophe; Pellacani, Giovanni; Longo, Caterina

2017-03-01

Irritant contact dermatitis is caused by skin barrier damage. Vitamin E is an antioxidant that is commonly used in cosmetics to prevent photo-damage. To show the usefulness of reflectance confocal microscopy in the assessment of irritant skin damage caused by sodium lauryl sulfate (SLS) and of the protective action of vitamin E applied prior to skin irritation. Ten healthy volunteers were enrolled. Irritation was induced by the application of a patch test containing SLS 5% aq. for 24 h. Three sites were compared: one site on which a product with vitamin E was applied before SLS treatment, one site on which the same product was applied after SLS treatment, and one control site (SLS only). Each site was evaluated with reflectance confocal microscopy, providing in vivo tissue images at nearly histological resolution. We also performed a computerized analysis of the VivaStack® images. Reflectance confocal microscopy is able to identify signs of skin irritation and the preventive effect of vitamin E application. Reflectance confocal microscopy is useful in the objective assessment of irritative skin damage. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Changes in hydration of the stratum corneum are the most suitable indicator to evaluate the irritation of surfactants on the skin.

PubMed

Fujimura, T; Shimotoyodome, Y; Nishijima, T; Sugata, K; Taguchi, H; Moriwaki, S

2017-02-01

Irritancy levels of surfactants on human skin have not been clarified completely. The relationships between skin damage and changes of skin properties caused by various surfactants were investigated using non-invasive measurements. Aqueous solutions of seven kinds of anionic, non-ionic, and amphoteric surfactants were exposed to the inside of forearm skin of 20 human subjects in two separate studies using the cup method. Hydration of the stratum corneum (SC), transepidermal water loss (TEWL), pH, skin surface roughness, and contents of the SC were measured before and after one exposure and after five and nine consecutive exposures to various surfactants. The discontinuation ratio of subjects for testing in each surfactant was determined by skin irritation symptoms and was defined as the degree of skin damage. Significant changes were observed only in hydration, TEWL, and natural moisturizing factors (NMF) content in the SC following surfactant exposure. A significant correlation was observed between the discontinuation ratio of each surfactant and the changes of hydration, TEWL, and NMF. Especially, the change of SC hydration showed an excellent correlation with the discontinuation ratio both for single (r = 0.942, P < 0.001) and for chronic exposures (r = 0.934, P < 0.001). Our results indicate that the change of hydration of the SC is equivalent to the skin damage caused by surfactants, and therefore is the most suitable indicator to evaluate the irritation of surfactants on the skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Measurement of cytotoxicity and irritancy potential of sugar-based surfactants on skin-related 3D models.

PubMed

Lu, Biao; Miao, Yong; Vigneron, Pascale; Chagnault, Vincent; Grand, Eric; Wadouachi, Anne; Postel, Denis; Pezron, Isabelle; Egles, Christophe; Vayssade, Muriel

2017-04-01

Sugar-based surfactants present surface-active properties and relatively low cytotoxicity. They are often considered as safe alternatives to currently used surfactants in cosmetic industries. In this study, four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or a maltose headgroup through an amide linkage, were synthesized and compared to two standard surfactants. The cytotoxic and irritant effects of surfactants were evaluated using two biologically relevant models: 3D dermal model (mouse fibroblasts embedded in collagen gel) and reconstituted human epidermis (RHE, multi-layered human keratinocytes). Results show that three synthesized surfactants possess lower cytotoxicity compared to standard surfactants as demonstrated in the 3D dermal model. Moreover, the IC50s of surfactants against the 3D dermal model are higher than IC50s obtained with the 2D dermal model (monolayer mouse fibroblasts). Both synthesized and standard surfactants show no irritant effects after 48h of topical application on RHE. Throughout the study, we demonstrate the difficulty to link the physico-chemical properties of surfactants and their cytotoxicity in complex models. More importantly, our data suggest that, prior to in vivo tests, a complete understanding of surfactant cytotoxicity or irritancy potential requires a combination of cellular and tissue models. Copyright © 2017 Elsevier Ltd. All rights reserved.

DERMATOLOGIC CHANGES IN THE CIRCUMILEOSTOMY SKIN

PubMed Central

McNamara, Robert J.; Farber, Eugene M.; Roland, Samuel I.

1959-01-01

A comprehensive questionnaire inquiring about difficulties with care of the skin in the area immediately surrounding the artificial anus was sent to ileostomy patients in the United States. Eighty per cent of 327 replying to the questionnaire had such difficulties. The problem of irritation is essentially that of intimate contact of fecal material with the circumileostomy skin, and associated factors are the potentially irritating materials used in the manufacture of ileostomy appliances, as well as the adhesives used to affix the appliance to the skin. Mechanical trauma incident to removal and reapplication of the appliance, as well as loosening of the disc and exposure of unprotected skin, accelerates the corrosive action of the material discharged. Changing the appliance before leakage or irritation occurs is helpful in preventing skin difficulties. In cases of long standing or repeated irritation, care must be taken to check the suitability of the appliance or the possibility of a complication in the stoma that could be corrected surgically. ImagesFigure 2.Figure 4. PMID:13662859

Catch-up validation study of an in vitro skin irritation test method based on an open source reconstructed epidermis (phase II).

PubMed

Groeber, F; Schober, L; Schmid, F F; Traube, A; Kolbus-Hernandez, S; Daton, K; Hoffmann, S; Petersohn, D; Schäfer-Korting, M; Walles, H; Mewes, K R

2016-10-01

To replace the Draize skin irritation assay (OECD guideline 404) several test methods based on reconstructed human epidermis (RHE) have been developed and were adopted in the OECD test guideline 439. However, all validated test methods in the guideline are linked to RHE provided by only three companies. Thus, the availability of these test models is dependent on the commercial interest of the producer. To overcome this limitation and thus to increase the accessibility of in vitro skin irritation testing, an open source reconstructed epidermis (OS-REp) was introduced. To demonstrate the capacity of the OS-REp in regulatory risk assessment, a catch-up validation study was performed. The participating laboratories used in-house generated OS-REp to assess the set of 20 reference substances according to the performance standards amending the OECD test guideline 439. Testing was performed under blinded conditions. The within-laboratory reproducibility of 87% and the inter-laboratory reproducibility of 85% prove a high reliability of irritancy testing using the OS-REp protocol. In addition, the prediction capacity was with an accuracy of 80% comparable to previous published RHE based test protocols. Taken together the results indicate that the OS-REp test method can be used as a standalone alternative skin irritation test replacing the OECD test guideline 404. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Potential allergy and irritation incidents among health care workers.

PubMed

Alamgir, Hasanat; Yu, Shicheng; Chavoshi, Negar; Ngan, Karen

2008-07-01

This study describes the types, causes, and outcomes of potential irritation and allergy incidents among workers in British Columbia's health care industry. Data on occupation-induced allergy and irritation incidents were extracted from a standardized database using the number of productive hours obtained from payroll data as a denominator during a 1-year period from three British Columbia health regions. Younger workers, female workers, facility support service workers, laboratory assistants and technicians, and maintenance and acute care workers were found to be at higher risk for allergy and irritation incidents. Major causes of allergy and irritation incidents included chemicals, blood and body fluids, food and objects, communicable diseases, air quality, and latex. A larger proportion of chemically induced incidents resulted in first aid care only, whereas non-chemical incidents required more emergency room visits.

Significance of hair-dye base-induced sensory irritation.

PubMed

Fujita, F; Azuma, T; Tajiri, M; Okamoto, H; Sano, M; Tominaga, M

2010-06-01

Oxidation hair-dyes, which are the principal hair-dyes, sometimes induce painful sensory irritation of the scalp caused by the combination of highly reactive substances, such as hydrogen peroxide and alkali agents. Although many cases of severe facial and scalp dermatitis have been reported following the use of hair-dyes, sensory irritation caused by contact of the hair-dye with the skin has not been reported clearly. In this study, we used a self-assessment questionnaire to measure the sensory irritation in various regions of the body caused by two model hair-dye bases that contained different amounts of alkali agents without dyes. Moreover, the occipital region was found as an alternative region of the scalp to test for sensory irritation of the hair-dye bases. We used this region to evaluate the relationship of sensitivity with skin properties, such as trans-epidermal water loss (TEWL), stratum corneum water content, sebum amount, surface temperature, current perception threshold (CPT), catalase activities in tape-stripped skin and sensory irritation score with the model hair-dye bases. The hair-dye sensitive group showed higher TEWL, a lower sebum amount, a lower surface temperature and higher catalase activity than the insensitive group, and was similar to that of damaged skin. These results suggest that sensory irritation caused by hair-dye could occur easily on the damaged dry scalp, as that caused by skin cosmetics reported previously.

[Cytotoxicity of chemicals used in household products: estimation of eye irritating potency of 25 chemicals tested during 1991-1996].

PubMed

Ikarashi, Y; Tsuchiya, T; Nakamura, A

1997-01-01

Cytotoxicity potential of chemicals was evaluated by determining the concentrations inducing 50% reduction of neutral red (NR) uptake into Chinese hamster fibroblast V79 cells compared with control culture (IC50). The results of cytotoxicity test for surfactants with the data produced by the in vivo Draize eye and skin irritation test were compared. There was a good correlation between cytotoxicity and eye irritation score obtained from the Draize test. In contrast, no correlation was observed between Draize skin irritation score and cytotoxic potential of chemicals. Therefore, the NR cytotoxicity test was regarded as a possible in vitro model for predicting eye irritation. Based on the IC50 values in the NR cytotoxicity test, the eye irritation classification (weak, moderate and strong) for each chemical used in household products has been established. We evaluated the cytotoxicity of 25 chemicals used for antimicrobial, rubber accelerator, rubber antioxidant, ultraviolet absorber etc. in household products, and estimated the eye irritating potency of these test chemicals according to the criterion.

Evaluation of 4-methylcyclohexanemethanol (MCHM) in a combined irritancy and Local Lymph Node Assay (LLNA) in mice.

PubMed

Johnson, Victor J; Auerbach, Scott S; Luster, Michael I; Waidyanatha, Suramya; Masten, Scott A; Wolfe, Mary S; Burleson, Florence G; Burleson, Gary R; Germolec, Dori R

2017-07-01

4-Methylcyclohexanemethanol (MCHM) is a flotation reagent used in fine coal beneficiation. On January 9, 2014, crude MCHM, a mixture containing predominantly MCHM, was inadvertently released into the Elk River, a municipal water source that serves about 300,000 people in the Charleston, WV area, resulting in temporary contamination of 15 percent of the state's tap water and causing significant dermal exposure. The current studies were undertaken to determine whether crude MCHM or MCHM has the potential to produce dermal irritancy and/or sensitization. BALB/c female mice were treated daily for 3 consecutive days by direct epicutaneous application of 25 μL of various concentrations of crude MCHM or MCHM to the dorsum of each ear. A mouse ear-swelling test was used to determine irritancy potential and was undertaken in combination with the standardized Local Lymph Node Assay (LLNA) to determine skin sensitizing potential. MCHM was found to produce skin irritation at concentrations above 20% and did not produce sensitization. Crude MCHM also produced irritation, although weaker, and in addition was found to be a weak to moderate skin sensitizer. The results are discussed in terms of potential human health hazard. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tandem Repeated Irritation Test (TRIT) Studies and Clinical Relevance: Post 2006.

PubMed

Reddy, Rasika; Maibach, Howard

2018-06-11

Single or multiple applications of irritants can lead to occupational contact dermatitis, and most commonly irritant contact dermatitis (ICD). Tandem irritation, the sequential application of two irritants to a target skin area, has been studied using the Tandem Repeated Irritation Test (TRIT) to provide a more accurate representation of skin irritation. Here we present an update to Kartono's review on tandem irritation studies since 2006 [1]. We surveyed the literature available on PubMed, Embase, Google Scholar, and the UCSF Dermatology library databases since 2006. The studies included discuss the tandem effects of common chemical irritants, organic solvents, occlusion as well as clinical relevance - and enlarge our ability to discern whether multiple chemical exposures are more or less likely to enhance irritation.

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

PubMed

Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

2018-04-01

To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster. This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40. The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38. The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

A catch-up validation study of an in vitro skin irritation test method using reconstructed human epidermis LabCyte EPI-MODEL24.

PubMed

Kojima, Hajime; Katoh, Masakazu; Shinoda, Shinsuke; Hagiwara, Saori; Suzuki, Tamie; Izumi, Runa; Yamaguchi, Yoshihiro; Nakamura, Maki; Kasahawa, Toshihiko; Shibai, Aya

2014-07-01

Three validation studies were conducted by the Japanese Society for Alternatives to Animal Experiments in order to assess the performance of a skin irritation assay using reconstructed human epidermis (RhE) LabCyte EPI-MODEL24 (LabCyte EPI-MODEL24 SIT) developed by the Japan Tissue Engineering Co., Ltd. (J-TEC), and the results of these studies were submitted to the Organisation for Economic Co-operation and Development (OECD) for the creation of a Test Guideline (TG). In the summary review report from the OECD, the peer review panel indicated the need to resolve an issue regarding the misclassification of 1-bromohexane. To this end, a rinsing operation intended to remove exposed chemicals was reviewed and the standard operating procedure (SOP) revised by J-TEC. Thereafter, in order to confirm general versatility of the revised SOP, a new validation management team was organized by the Japanese Center for the Validation of Alternative Methods (JaCVAM) to undertake a catch-up validation study that would compare the revised assay with similar in vitro skin irritation assays, per OECD TG No. 439 (2010). The catch-up validation and supplementary studies for LabCyte EPI-MODEL24 SIT using the revised SOPs were conducted at three laboratories. These results showed that the revised SOP of LabCyte EPI-MODEL24 SIT conformed more accurately to the classifications for skin irritation under the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS), thereby highlighting the importance of an optimized rinsing operation for the removal of exposed chemicals in obtaining consistent results from in vitro skin irritation assays. Copyright © 2013 John Wiley & Sons, Ltd.

The effect of adhesive dressing edges on cutaneous irritancy and skin barrier function.

PubMed

Dykes, P J

2007-03-01

To assess the effect of repeated application and removal of adhesive edges from wound-care products on cutaneous irritancy and barrier function in normal volunteer subjects. This was a study using a 'repeat-insult patch test'. Adhesive edges from six commonly used wound-care products were applied continuously to the same site (six applications over a 14-day period) in 30 normal volunteer subjects. The test sites were assessed clinically before product reapplication using established ranking scales for cutaneous erythema. The cumulative irritancy score (CIS) for each test site was determined by adding the erythema scores at days 3, 5, 8, 10, 12 and 15. At the study end the barrier function of each test site was assessed by measuring transepidermal water loss (TEWL). The CIS showed that the products fall into two distinct groups, with Mepilex, Tielle and Allevyn giving low scores and Biatain, Comfeel and DuoDERM higher scores. Statistical analysis indicated significant differences (p < 0.05) between Mepilex and Biatain, Mepilex and Comfeel, Mepilex and DuoDERM, Tielle and Biatain, Allevyn and Biatain. The mean TEWL values also indicated that the products fall into two distinct groups: Mepilex, Tielle and Allevyn with low mean values close to that of normal adjacent back skin and Biatain, Comfeel and DuoDERM with much higher mean values. Statistical analysis indicated that Mepilex, Tielle and Allevyn were not significantly different from normal skin (p < 0.05), whereas Biatain, Comfeel and DuoDERM were significantly higher than normal skin and the other products tested. The results show clear differences between products; the clinical scores and TEWL measurements indicate that the products fall into two distinct groups. This novel approach seems able to discriminate between adhesive borders and may be useful during product development and in selecting products for clinical trials.

In vivo immunomodulatory, cumulative skin irritation, sensitization and effect of d-limonene on permeation of 6-mercaptopurine through transdermal drug delivery.

PubMed

Chandrashekar, N S; Hiremath, Shobha Rani Rajeev

2008-04-01

Using skin as a port for systemic drug administration, transdermal drug delivery has expanded greatly over the last two decades. Our aim was to formulate the single layer drug-in-adhesive transdermal patch for 6-mercaptopurine (6-MP). In vitro permeation study was carried out using modified Franz diffusion cell with and without of different concentration of d-limonene in human cadaver skin. In vivo immunomodulatory was carried out in mice, cumulative skin irritation, sensitization and patch adherence study was done in both mice and human subjects. 6-MP flux increased from 43+/-12.2 microg/cm2h (control) to 162.8+/-32.2 microg/cm2h (6% w/v d-limonene) data was significant (p<0.05), with decrease in the lag time to 35+/-9.3 min compared to control of 90 +/-15.3 min. In vivo immunomodulatory effect was shown in the Balb/c mice with 100 mumol/kg/body wt of animal for 5d (one dose/d) of d-limonene. WBC count of 13469 cells/mm peak was observed on 12th day, bone marrow cells of 26.3 x 10(6) cells/femur and alpha-esterase positive cells of 1259+/-328.4 cells/4000 bone marrow cells. Cumulative skin irritation, sensitisation and patch adherence in animals and human subjects showed no skin irritation and sensitization. Patch adhesion was greater than 90.0% respectively in both human subjects and mice. The percentage of human subjects with adhesive residue was significantly less with scores of zero. d-Limonene proved as good chemical enhancer by increasing in the skin permeability with shortened the lag time. It proved that therapeutic amount of 6-MP can be delivered through transdermal drug delivery.

Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance.

PubMed

Todosijević, Marija N; Savić, Miroslav M; Batinić, Bojan B; Marković, Bojan D; Gašperlin, Mirjana; Ranđelović, Danijela V; Lukić, Milica Ž; Savić, Snežana D

2015-12-30

To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester- over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81±5.97 and 60.86±3.67 vs. 27.00±5.09μg/cm(2), and its maximum plasma concentrations 275.57±109.49 and 281.31±76.76 vs. 150.23±69.74ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-02-01

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

Skin Color and Pigmentation in Ethnic Skin.

PubMed

Visscher, Marty O

2017-02-01

Skin coloration is highly diverse, partly due to the presence of pigmentation. Color variation is related to the extent of ultraviolet radiation exposure, as well as other factors. Inherent skin coloration arises from differences in basal epidermal melanin amount and type. Skin color is influenced by both the quantity and distribution of melanocytes. The effectiveness of inherent pigmentation for protecting living cells also varies. This article discusses skin color, pigmentation, and ethnicity in relation to clinical practice. Color perception, skin typing/classification, and quantitation of pigmentation are reviewed in relation to ethnicity, environmental stresses/irritants, and potential treatment effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Alternatives to In Vivo Draize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

PubMed Central

Lee, Miri; Hwang, Jee-Hyun; Lim, Kyung-Min

2017-01-01

Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility. PMID:28744350

Do local meteorological conditions influence skin irritation caused by transdermal rivastigmine? A retroprospective, pilot study.

PubMed

Segers, Kurt; Cytryn, Ephraim; Surquin, Murielle

2012-06-01

This retrospective study aimed to evaluate the incidence of transdermal rivastigmine treatment withdrawal secondary to adverse skin reactions among the patients from our Memory Clinic. In addition, we tested whether climatic conditions might have an influence on skin irritations leading to eventual treatment disruption. We performed a retrospective review of patients from the Brugmann University Hospital Memory Clinic having started transdermal rivastigmine between June 2008 and December 2010. Local meteorological data were provided by the Royal Meteorological Institute of Belgium. A total of 26.9% of the patients experienced adverse skin reactions at the rivastigmine application site, leading to treatment discontinuation in 19.2% of the cases. Rivastigmine cutaneous tolerability was not found to be related to demographic parameters, Mini Mental Status Examination score, or type of dementia. High temperature and low air humidity during the first month of treatment were found to be associated with a higher incidence of skin reactions and secondary treatment disruption. Transdermal rivastigmine induced a higher incidence of cutaneous adverse events than previously reported in a prospective clinical trial. Moreover, it seems that meteorological conditions favoring skin perspiration (high temperature and low air humidity) during the first month of treatment might have an influence on transdermal rivastigmine skin tolerability.

Does lactobionic acid affect the colloidal structure and skin moisturizing potential of the alkyl polyglucoside-based emulsion systems?

PubMed

Tasic-Kostov, M Z; Reichl, S; Lukic, M Z; Jaksic, I N; Savic, S D

2011-11-01

Moisturizing creams are the most prescribed products in dermatology, essential in maintaining healthy skin as well as in the topical treatment of some diseases. The irritation potential of commonly used emulsifiers and moisturizing ingredients, but also their mutual interactions, could affect the functionality and safety of those dermopharmaceutics. The aim of this study was to promote moisturizing alkyl polyglucoside (APG)-based emulsion as vehicle for lactobionic acid (LA), advantageous representative of the alphahydroxyacids (AHAs)-multifunctional moisturizers, assessing the safety for use (in vitro acute skin irritation test using cytotoxicity assay compared with in vivo data obtained using skin bioengineering methods) and in vivo moisturizing capacity (bioengineering of the skin). In order to investigate possible interactions between APG mild natural emulsifier-based emulsion and LA, a deeper insight into the colloidal structure of the placebo and the emulsion with LA was given using polarization and transmission electron microscopy, rheology, thermal and texture analysis. This study showed that APG-based emulsions could be promoted as safe cosmetic/dermopharmaceutical vehicles and carriers for extremely acidic and hygroscopic AHA class of actives (specifically LA); prospective safety for human use of both APG and LA with the correlation between in vivo and in vitro findings was shown. However, it was revealed that LA strongly influenced the colloidal structure of the emulsion based on APGs and promoted the formation of lamellar structures which reflects onto the mode of water distribution within the cream. The advantageous skin hydrating potential of LA-containing emulsion vs. placebo was unlikely to be achieved, pointing that emulsions stabilized by lamellar liquid crystalline structures probably are not satisfying carriers for highly hygroscopic actives in order to reach the full moisturizing potential. Safe and effective use on dry skin is presumed.

Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel.

PubMed

Queille-Roussel, C; Poncet, M; Mesaros, S; Clucas, A; Baker, M; Soloff, A M

2001-02-01

Adapalene is a naphthoic acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris. This study assessed the cumulative irritation potential of adapalene gel (0.1%) and adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%) solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). This was a single-center, randomized, controlled, investigator-blinded, intraindividual comparison study in healthy subjects with normal skin. The cumulative irritation assay (patch test) was used to assess the potential for irritation (including erythema) of the treatments. Each subject received all study treatments, randomly applied under occlusion (patch), to sites on either side of the midline on the mid-thoracic area of the back. All patches were applied to the same sites throughout the study, unless the degree of reaction to the treatment or adhesive necessitated removal. For 3 weeks, each test material was applied daily, Monday through Friday, for approximately 24 hours; the Friday patches were left in place over the weekend for approximately 72 hours. All 36 subjects (26 men, 10 women; age, 18-49 years [mean, 30 years]) completed the study. In the course of the study, all subjects had > or =1 application discontinued prematurely on > or =1 site due to intolerance. There were no discontinuations with white petrolatum. All erythromycin/tretinoin gel patches were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were discontinued at day 11 or day 17. The adapalene products, although slightly more irritating (mean cumulative irritation index, 0.25-1) than white petrolatum, were significantly less irritating than the erythromycin/tretinoin and erythromycin/isotretinoin products (P < 0.01). Adapalene gel and cream were well tolerated

Irritant contact dermatitis in warehouse employees.

PubMed

Ashworth, J; Rycroft, R J; Waddy, R S; Irvine, D

1993-02-01

A detailed survey of skin complaints amongst 114 airline employees working in a new warehouse revealed 26 cases of skin problems which originated during the 2 1/2 year operation. A clinical survey of broadly the same population confirmed 14 cases from 98 employees as chronic irritant contact dermatitis of the hands. The work involved the reception, unpackaging, inspection, repackaging and dispatch of aircraft parts. The source of the skin irritation was not to be found in the work itself. Rather, the presence among the employees of two severe cases of non-occupational eczema, combined with the idea that incoming aircraft parts from foreign countries might be 'dirty' in some way, had caused a heightened perception of a risk of skin disease, and the frequency of hand washing had increased as a result. Over-frequent hand washing in a few employees had resulted in precisely what the warehouse staff had been trying to avoid.

Survey of ocular irritation predictive capacity using Chorioallantoic Membrane Vascular Assay (CAMVA) and Bovine Corneal Opacity and Permeability (BCOP) test historical data for 319 personal care products over fourteen years.

PubMed

Donahue, D A; Kaufman, L E; Avalos, J; Simion, F A; Cerven, D R

2011-03-01

The Chorioallantoic Membrane Vascular Assay (CAMVA) and Bovine Corneal Opacity and Permeability (BCOP) test are widely used to predict ocular irritation potential for consumer-use products. These in vitro assays do not require live animals, produce reliable predictive data for defined applicability domains compared to the Draize rabbit eye test, and are rapid and inexpensive. Data from 304 CAMVA and/or BCOP studies (319 formulations) were surveyed to determine the feasibility of predicting ocular irritation potential for various formulations. Hair shampoos, skin cleansers, and ethanol-based hair styling sprays were repeatedly predicted to be ocular irritants (accuracy rate=0.90-1.00), with skin cleanser and hair shampoo irritation largely dependent on surfactant species and concentration. Conversely, skin lotions/moisturizers and hair styling gels/lotions were repeatedly predicted to be non-irritants (accuracy rate=0.92 and 0.82, respectively). For hair shampoos, ethanol-based hair stylers, skin cleansers, and skin lotions/moisturizers, future ocular irritation testing (i.e., CAMVA/BCOP) can be nearly eliminated if new formulations are systematically compared to those previously tested using a defined decision tree. For other tested product categories, new formulations should continue to be evaluated in CAMVA/BCOP for ocular irritation potential because either the historical data exhibit significant variability (hair conditioners and mousses) or the historical sample size is too small to permit definitive conclusions (deodorants, make-up removers, massage oils, facial masks, body sprays, and other hair styling products). All decision tree conclusions should be made within a conservative weight-of-evidence context, considering the reported limitations of the BCOP test for alcohols, ketones, and solids. Copyright © 2010 Elsevier Ltd. All rights reserved.

Norartocarpetin from a folk medicine Artocarpus communis plays a melanogenesis inhibitor without cytotoxicity in B16F10 cell and skin irritation in mice

PubMed Central

2013-01-01

Background Many natural products used in preventive medicine have also been developed as cosmeceutical ingredients in skin care products, such as Scutellaria baicalensis and Gardenia jasminoides. Norartocarpetin is one of the antioxidant and antityrosinase activity compound in Artocarpus communis; however, the cytotoxicity, skin irritation and antimelanogenesis mechanisms of norartocarpetin have not been investigated yet. Methods In the present study, cell viability in vitro and skin irritation in vivo are used to determine the safety of norartocarpetin. The melanogenesis inhibition of norartocarpetin was determined by cellular melanin content and tyrosinase in B16F10 melanoma cell. Moreover, we examined the related-melanogenesis protein by western blot analysis for elucidating the antimelanogenesis mechanism of norartocarpin. Results The result of the present study demonstrated that norartocarpetin not only present non-cytotoxic in B16F10 and human fibroblast cells but also non-skin irritation in mice. Moreover, our result also first found that norartocarpetin downregulated phospho-cAMP response element-binding (phospho-CREB) and microphthalmia-associated transcription factor (MITF) expression, which in turn decreased both synthesis of tyrosinases (TRP-1 and TRP-2) and cellular melanin content. This process is dependent on norartocarpetin phosphorylation by mitogen-activated protein kinases such as phospho-JNK and phospho-p38, and it results in decreased melanogenesis. Conclusion The present study suggests that norartocarpetin could be used as a whitening agent in medicine and/or cosmetic industry and need further clinical study. PMID:24325567

Classification of sensitizing and irritative potential in a combined in-vitro assay

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

Wanner, Reinhard, E-mail: reinhard.wanner@charite.d; Sonnenburg, Anna; Quatchadze, Maria

2010-06-01

We have developed a coculture system which in parallel indicates the sensitizing and irritative potential of xenobiotics. The assay is named loose-fit coculture-based sensitization assay (LCSA) and may be performed within 5 days. The system is composed of human monocytes that differentiate to a kind of dendritic cells by 2-day culturing in the presence of allogenic keratinocytes. The culture medium is enriched by a cocktail of recombinant cytokines. On day 3, concentration series of probes are added. On day 5, cells are harvested and analyzed for expression range of CD86 as a marker of sensitizing potential and for uptake ofmore » the viability stain 7-AAD as a marker of irritative potential. Estimation of the concentration required to cause a half-maximal increase in CD86 expression allowed quantification of sensitizing potential, and estimation of the concentration required to reduce viability to 50% allowed quantification of irritative potential. Examination of substances with known potential resulted in categorization of test scores. To evaluate our data, we have compared results with those of the validated animal-based sensitization test, the murine local lymph node assay (LLNA, OECD TG 429). To a large extent, results from LCSA and from LLNA achieved analogous grouping of allergens into categories like weak-moderate-strong. However, the new assay showed an improved capacity to distinguish sensitizers from non-sensitizers and irritants. In conclusion, the LCSA contains potential to fulfil the requirements of the EU's programme for the safety of chemicals 'Registration, Evaluation, Authorisation and Restriction of chemical substances' (REACH, 2006) to replace animal models.« less

Irritancy potential of 17 detergents used commonly by the Indian household.

PubMed

Austoria, A J; Lakshmi, Chembolli; Srinivas, C R; Anand, C V; Mathew, A C

2010-01-01

Detergents are used by almost every household in the developed and developing world. Soap and most detergents are anionic surfactants and attack the horny layer of the skin and increase its permeability with little or no inflammatory change and may result in hand eczema, which is very distressing and incapacitating. To evaluate the irritant potential of common household detergents (laundry and dish wash) used by the Indian population using a 24-hour patch test and to convincingly educate the patients on the detergents less likely to cause irritation in the particular individual. Seventeen commonly used detergents found in Indian market were included in the study, of which, 12 were laundry detergents (powders--seven, bar soap--five) and five were dish wash detergents (powder--one, liquid--one, bar soap--three). The irritant potential of the 17 detergents were evaluated in 30 volunteers. Thirty microliters of each of the detergent bar solutions, distilled water (negative control), and 20% SDS (positive control) were applied to Finn chambers with a micropipette and occluded for 24 hours. Erythema, scaling, and edema were graded in comparison to the reaction at the negative control site (distilled water) for each volunteer separately. The scoring of erythema/dryness and wrinkling on a 0-4 point scale and edema on another 0-4 point scale was based on the Draize scale. The pH of each of the detergent solutions was determined using litmus papers (Indikrom papers from Qualigens fine chemicals). The difference between detergents (F value) was significant for erythema/dryness and wrinkling (F = 3.374; p = 0.000), but not significant for edema (F = 1.297; p = 0.194). [Table 2] lists the means for erythema/dryness and wrinkling, and edema. The F value of the totals of the means for erythema/dryness and wrinkling and edema was significant (F = 2.495; p = 0.001). The pH of all the detergents was found to be alkaline except Pril utensil cleaner which tested acidic (pH 6). The

Additive impairment of the barrier function and irritation by biogenic amines and sodium lauryl sulphate: a controlled in vivo tandem irritation study.

PubMed

Fluhr, J W; Kelterer, D; Fuchs, S; Kaatz, M; Grieshaber, R; Kleesz, P; Elsner, P

2005-01-01

Biogenic amines are potential irritants e.g. in fish-, meat-, milk- and egg-processing professions like cooks, butchers and bakers. The aim of this study was to test the irritative and barrier-disrupting properties of the biogenic amines ammonium hydroxide (AM), dimethylamine (DMA) and trimethylamine (TMA). A repeated sequential irritation of 30 min twice per day was performed over a total of 4 days (tandem repeated irritation test) on the back of 20 healthy volunteers of both sexes with AM, DMA, TMA and sodium lauryl sulphate (SLS). The epidermal barrier function was assessed with a Tewameter TM 210, stratum corneum surface pH was measured with a Skin-pH-Meter 900, inflammation was assessed with a Chromameter CR-300 on the a* axis for redness and a visual score was recorded. All tested biogenic amines (AM, DMA and TMA) induced a barrier disruption and a pH increase paralleled with a 1-day-delayed onset of inflammatory signs. These effects were further enhanced and accelerated by a sequential application of SLS together with the biogenic amines, and inflammation occurred earlier than with the single compounds. Acetic acid (AA) in contrast did only show mild barrier disruption and no significant inflammatory signs. Our system allowed a ranking of the different compounds in their irritative potential in the tandem irritation with SLS: SLS > NaOH > TMA > AA > AM > DMA. The results are suggestive that in the food-processing industry the simultaneous contact with biogenic amines and harmful detergents like SLS should be minimized. Copyright 2005 S. Karger AG, Basel.

Irritancy and Allergic Responses Induced by Topical Application of ortho-Phthalaldehyde

PubMed Central

Anderson, Stacey E.; Umbright, Christina; Sellamuthu, Rajendran; Fluharty, Kara; Kashon, Michael; Franko, Jennifer; Jackson, Laurel G.; Johnson, Victor J.; Joseph, Pius

2010-01-01

Although ortho-phthalaldehyde (OPA) has been suggested as an alternative to glutaraldehyde for the sterilization and disinfection of hospital equipment, the toxicity has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of OPA. The EpiDerm Skin Irritation Test was used to evaluate in vitro irritancy potential of OPA and glutaraldehyde. Treatment with 0.4125 and 0.55% OPA induced irritation, while glutaraldehyde exposure at these concentrations did not. Consistent with the in vitro results, OPA induced irritancy, evaluated by ear swelling, when mice were treated with 0.75%. Initial evaluation of the sensitization potential was conducted using the local lymph node assay at concentrations ranging from 0.005 to 0.75%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.051% compared to that of 0.089%, previously determined for glutaraldehyde. Immunoglobulin (Ig) E-inducing potential was evaluated by phenotypic analysis of draining lymph node (DLN) cells and measurement of total and specific serum IgE levels. The 0.1 and 0.75% exposed groups yielded significant increases in the IgE+B220+ cell population in the lymph nodes while the 0.75% treated group demonstrated significant increases in total IgE, OPA-specific IgE, and OPA-specific IgG1. In addition, significant increases in interleukin-4 messenger RNA and protein expression in the DLNs were observed in OPA-treated groups. The results demonstrate the dermal irritancy and allergic potential of OPA and raise concern about the proposed/intended use of OPA as a safe alternative to glutaraldehyde. PMID:20176622

Are Cosmetics Used in Developing Countries Safe? Use and Dermal Irritation of Body Care Products in Jimma Town, Southwestern Ethiopia

PubMed Central

Amasa, Wayessa; Santiago, Dante; Mekonen, Seblework; Ambelu, Argaw

2012-01-01

Background. Rabbit skin model was used to test skin irritation of the most commonly used cosmetic products in Jimma town, southwestern Ethiopia. The most commonly used cosmetics were Dove, Glysolid, College, Top Society, Fair and Lovely, Nivea, Lux, Magic fruit world, Solea, Body talk, Kris, Holly, Victoria, and Sweet Heart. Methods. Intact and abraded rabbit skins were tested for erythema and edema under shade and under sun exposure. Draize Primary Irritation Index (PII) was used to calculate skin irritation of each cosmetic. Cosmetic ingredients were analyzed from the labels. Results and Discussion. Only Dove cream caused no skin irritation except for an abraded skin under sun exposure for five consecutive days. It has been identified that application of cosmetics on abraded skin under sunny condition worsens the irritation. Cosmetic labels revealed that most ingredients used in all products were those restricted chemicals due to their adverse health effects. Conclusion. This study has concluded that use of cosmetics under sunshine and also on abraded skin increases skin irritation. Hence, those users who have abraded skin are advised not to apply those cosmetics on continuous basis specifically under sun exposure. PMID:23209460

4-Day evaluation of the irritation potential of topical desoximetasone 0.25% and 0.05% spray on light-exposed skin.

PubMed

Patel, Nupur U; Grammenos, Alexandra; Gowda, Asha; Onikoyi, Omobola; Feldman, Steven R

2018-06-01

The safety and potential side effects of desoximetasone 0.25% and 0.05% sprays have not previously been studied. The primary objective of this study was to determine the irritation potential of desoximetasone 0.25%, 0.05% and vehicle sprays in response to irradiation. Thirty-four subjects were enrolled in the study, each with three study treatments (desoximetasone 0.25%, 0.05% topical sprays and vehicle) were applied to two sites each on the back of every subject, with half of the sites irradiated with filtered UV light. Dermal reactions at the test sites were evaluated using a visual scale with corresponding numerical scores that rated the degree of erythema and oedema. Desoximetasone 0.25%, 0.05%, and vehicle caused no detectable signs of phototoxicity when examined on days 3 and 4. Mean scores of desoximetasone 0.25%, 0.05% and vehicle to non-irradiated treatment areas showed no signs of irritation. Our results suggest that regular application of desoximetasone 0.25% and 0.05% topical sprays do not induce photosensitization or photoirritation. The safety of this topical spray may help with clinical management of patients using topical corticosteroids while also receiving therapeutic UV light exposure. Thus, patients can use desoximetasone sprays without concerns of side effects due to therapeutic light or sun exposure.

[Incidence of irritant dermatosis among employees of the shipbuilding industry].

PubMed

Heise, H; Kühne, G; Kröger, D

1983-10-01

Irritant dermatosis is a non-specific reactive change on the skin. In most cases it represents the summated effects induced by various agents. Not only the shortened recovery phases of the skin but also a dispositional factor are important. Such changes, which are relatively common in some vocations but are usually only slight, cannot, as a rule, be regarded as signs of illness. Nevertheless, attention should be drawn to the necessity of intensive skin care and observation of the recovery phases because the frequency of irritant dermatosis can increase with increasing length of employment.

Managing Occupational Irritant Contact Dermatitis Using a Two-Step Skincare Regimen Designed to Prevent Skin Damage and Support Skin Recovery.

PubMed

von Grote, Erika C; Palaniswarmy, Kiruthi; Meckfessel, Matthew H

2016-12-01

Occupational irritant contact dermatitis (ICD) affecting the hands is a common and difficult-to-manage condition. Occupations that necessitate contact with harsh chemicals, use of alcohol-based disinfectants, and frequent hand washing elevate the risk of ICD. Management strategies that do not adequately prevent accumulated damage and repair skin, can develop into chronic dermatoses which negatively impact work productivity and quality of life. A 2-step skin-care regimen (Excipial Daily Protection Hand Cream (EP) and Excipial Rapid Repair Hand Cream (ER), Galderma Laboratories, L.P.) has been developed as a daily-use management strategy to protect and repair vulnerable hands. The protective barrier cream is formulated with aluminum chlorohydrate and designed for pre-exposure application to enhance the skin's natural protective barrier and minimize excessive moisture while wearing protective gloves. The repair cream, a lipid-rich formulation, is intended for post-exposure application to rehydrate and facilitate the skin's natural healing process. The results of 3 clinical studies highlighted in this review demonstrate how the use of a 2-step skin-care regimen offers a greater protective effect against ICD than the use of barrier cream alone, and also how the formulation of the barrier cream used in these studies helps minimize the occlusion effect caused by gloves and does not interfere with the antibacterial efficacy of an alcohol-based hand sanitizer. This 2-step skin-care regimen is effectively designed to manage and minimize the risk of ICD development in a variety of patients and provides clinicians an additional tool for helping patients manage ICD. J Drugs Dermatol. 2016;15(12):1504-1510.

A comprehensive evaluation of the carcinogenic potential of middle distillate fuels.

PubMed

Nessel, C S

1999-02-01

Middle distillate fuels (MDFs), which include jet fuel, kerosene, and diesel fuel, are a class of hydrocarbons distilled from crude oil at approximately 350-700 degrees F (176-371 degrees C). Although MDFs generally do not contain appreciable levels of potentially carcinogenic polycyclic aromatic compounds (PACs), they have produced weak tumorigenic responses in mouse skin characterized by low tumor yield and long latency. Recent studies demonstrated that the tumorigenic effects of these MDFs were dependent upon chronic dermal irritation. In the absence of skin irritation, tumors did not develop. Mechanistic studies suggest that straight-run MDFs containing low levels of PACs cause skin tumors through a nongenotoxic mechanism. MDFs cause chronic skin irritation and injury with repeated application to the skin. They have been found to have little or no activity in the modified Ames mutagenicity assay, lack tumor initiating activity, and are active skin tumor promoters. It has been hypothesized that the tumorigenic response to MDFs results from the promotion of preexisting, spontaneously initiated cells. Two recent studies, a one-year tumor promotion study and a two-year skin painting study, evaluated the role of skin irritation on the tumorigenic activity of MDFs in mice. MDFs were applied in pure and diluted forms to assess the effect of equal weekly doses of irritating and nonirritating test materials. The tumorigenicity of straight-run MDFs correlated to the level of skin irritation. No significant increase in tumor incidence occurred under conditions that resulted in minimal skin irritation and injury. These studies indicate that the tumorigenic activity of MDFs containing low levels of PACs is secondary to chronic skin irritation. These materials should not present a carcinogenic hazard in the absence of prolonged skin irritation.

Occupational skin hazards and prevalence of occupational skin diseases in shoe manufacturing workers in Indonesia.

PubMed

Febriana, Sri Awalia; Soebono, Hardyanto; Coenraads, Pieter-Jan

2014-02-01

Shoe manufacturing workers are exposed daily to an extensive range of potential physical and chemical occupational hazards. Shoe manufacturing in Indonesia is one of the industrial sectors that has shown sustained growth amongst the newly industrialized countries (NICs). In this study, we investigated the possible potential exposure of the workers to physical and occupational hazards and determined the prevalence of occupational skin diseases at a shoe manufacturing factory in Indonesia. A cross-sectional study on the observation of the working process and an inventory and risk assessment of exposure to the chemicals used. Classification of chemicals as potential sensitizers/irritants and qualitative assessments of these chemicals were done. Workers were examined and interviewed using the Nordic Occupational Skin Questionnaire-2002/LONG. The risk of Occupational skin diseases (OSD) at the shoe factory was mainly related to the exposure of the workers' skin to potential physical and chemical hazards in hot and humid environmental conditions. From a total of 514 workers, 8.5 % reported current OSD and 4.8 % reported a history of OSD. Occupational skin diseases were diagnosed in 29 % of the workers by dermatologists and 7.6 % had an occupational contact dermatitis (OCD). Of the 39 workers with contact dermatitis, 33 consented to being patch tested, 14 (3 %) workers showed a positive results and considered as having an occupational allergic contact dermatitis (OACD) and 25 (4.9 %) had an occupational irritant contact dermatitis (OICD). We observed a repeated and prolonged exposure of the workers to numerous physical and chemical skin hazards at this factory.

Investigation of the predictive validity of laser-EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers.

PubMed

Schaffler, Klaus; Nicolas, Laurent B; Borta, Andreas; Brand, Tobias; Reitmeir, Peter; Roebling, Robert; Scholpp, Joachim

2017-07-01

The aim of the present study was to assess the predictivity of laser-(radiant-heat)-evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti-nociceptive/anti-hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types. This was a randomized, placebo-controlled, single-blind, five-way-crossover trial. Twenty-five healthy male/female Caucasians were included (receiving celecoxib 200 mg, pregabalin 150 mg, duloxetine 60 mg, lacosamide 100 mg or placebo) in a Williams design, with CO 2 laser-induced painful stimuli to normal, ultraviolet (UV) B-inflamed and capsaicin-irritated skin. LEPs and visual analogue scale ratings were taken at baseline and hourly for 6 h postdose from all three skin types. In normal skin, the averaged postdose LEP peak-to-peak-(PtP)-amplitudes were reduced by pregabalin (-2.68 μV; 95% confidence interval (CI) -4.16, 1.19) and duloxetine (-1.73 μV; 95% CI -3.21, -0.26) but not by lacosamide and celecoxib vs. placebo. On UVB-irradiated skin, reflecting inflammatory pain, celecoxib induced a pronounced reduction in LEP PtP amplitudes vs. placebo (-6.2 μV; 95% CI -7.88, -4.51), with a smaller reduction by duloxetine (-4.54 μV; 95% CI -6.21, -2.87) and pregabalin (-3.72 μV; 95% CI -5.40, -2.04), whereas lacosamide was inactive. LEP PtP amplitudes on capsaicin-irritated skin, reflecting peripheral/spinal sensitization, as in neuropathic pain, were reduced by pregabalin (-3.78 μV; 95% CI -5.31, -2.25) and duloxetine (-2.32 μV; 95% CI -3.82, -0.82) but not by celecoxib or lacosamide vs. placebo, which was in agreement with known clinical profiles. Overall, PtP amplitude reductions were in agreement with subjective ratings. LEP algesimetry is sensitive to analgesics with different modes of action and may enable the effects of novel analgesics to be assessed during early clinical

Six week evaluation of the potential for topical desoximetasone 0.25% spray to induce photoallergic skin reaction.

PubMed

Patel, Nupur U; Gowda, Asha; Grammenos, Alexandra; Onikoyi, Omobola; Feldman, Steven R

2018-05-01

Desoximetasone 0.25% topical spray is a novel formulation that has not been tested or approved for safety and efficacy. The primary objective was to determine the potential of desoximetasone 0.25 and 0.05% topical sprays, as well as a vehicle to induce photoallergic skin reaction after repeated topical application and irradiation to the skin using a controlled photopatch testing procedure. 53 subjects completed the study, each with six application sites (two of each treatment), three of which were irradiated and three non-irradiated, for an induction period of three weeks and then challenge period at week 6. Desoximetasone 0.25 and 0.05%, as well as vehicle showed no evidence of potential to induce photosensitization. There was statistically significantly greater irritation at the vehicle irradiated site in comparison to the irradiated treatment area of desoximetasone 0.25% (p = .005) and the irradiated treatment area of desoximetasone 0.05% (p = .008). Our results suggest that regular treatment with desoximetasone 0.25 and 0.05% spray, followed by UV light exposure does not induce photosensitization or photo-irritation. These findings increase confidence for the use of this topical spray in eczema or psoriasis patients who may also be receiving UV light therapy and may contribute to the clinical management of these patients.

Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants

PubMed Central

Willis, Daniel N.; Liu, Boyi; Ha, Michael A.; Jordt, Sven-Eric; Morris, John B.

2011-01-01

Menthol, the cooling agent in peppermint, is added to almost all commercially available cigarettes. Menthol stimulates olfactory sensations, and interacts with transient receptor potential melastatin 8 (TRPM8) ion channels in cold-sensitive sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing channel. It is highly controversial whether menthol in cigarette smoke exerts pharmacological actions affecting smoking behavior. Using plethysmography, we investigated the effects of menthol on the respiratory sensory irritation response in mice elicited by smoke irritants (acrolein, acetic acid, and cyclohexanone). Menthol, at a concentration (16 ppm) lower than in smoke of mentholated cigarettes, immediately abolished the irritation response to acrolein, an agonist of TRPA1, as did eucalyptol (460 ppm), another TRPM8 agonist. Menthol's effects were reversed by a TRPM8 antagonist, AMTB. Menthol's effects were not specific to acrolein, as menthol also attenuated irritation responses to acetic acid, and cyclohexanone, an agonist of the capsaicin receptor, TRPV1. Menthol was efficiently absorbed in the respiratory tract, reaching local concentrations sufficient for activation of sensory TRP channels. These experiments demonstrate that menthol and eucalyptol, through activation of TRPM8, act as potent counterirritants against a broad spectrum of smoke constituents. Through suppression of respiratory irritation, menthol may facilitate smoke inhalation and promote nicotine addiction and smoking-related morbidities.— Willis, D. N., Liu, B., Ha, M. A., Jordt, S.-E., Morris, J. B. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. PMID:21903934

Skin Conditions

MedlinePlus

Your skin is your body's largest organ. It covers and protects your body. Your skin Holds body fluids in, preventing dehydration Keeps harmful ... it Anything that irritates, clogs, or inflames your skin can cause symptoms such as redness, swelling, burning, ...

Airborne irritant contact dermatitis due to synthetic fibres from an air-conditioning filter.

PubMed

Patiwael, Jiska A; Wintzen, Marjolein; Rustemeyer, Thomas; Bruynzeel, Derk P

2005-03-01

We describe 8 cases of occupational airborne irritant contact dermatitis in intensive care unit (ICU) employees caused by synthetic (polypropylene and polyethylene) fibres from an air-conditioning filter. Not until a workplace investigation was conducted, was it possible to clarify the unusual sequence of events. High filter pressure in the intensive care air-conditioning system, maintained to establish an outward airflow and prevent microorganisms from entering the ward, probably caused fibres from the filter to become airborne. Upon contact with air-exposed skin, fibres subsequently provoked skin irritation. Test periods in the ICU with varying filter pressures, in an attempt to improve environmental conditions, led to even higher filter pressure levels and more complaints. The sometimes-very-low humidity might have contributed to development of skin irritation. The fact that most patients recovered quickly after treatment with emollients and changing the filters made it most likely that the airborne dermatitis was of an irritant nature.

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).

Anti-irritant and anti-inflammatory effects of glycerol and xylitol in sodium lauryl sulphate-induced acute irritation.

PubMed

Szél, E; Polyánka, H; Szabó, K; Hartmann, P; Degovics, D; Balázs, B; Németh, I B; Korponyai, C; Csányi, E; Kaszaki, J; Dikstein, S; Nagy, K; Kemény, L; Erős, G

2015-12-01

Glycerol is known to possess anti-irritant and hydrating properties and previous studies suggested that xylitol may also have similar effects. Our aim was to study whether different concentrations of these polyols restore skin barrier function and soothe inflammation in sodium lauryl sulphate (SLS)-induced acute irritation. The experiments were performed on male SKH-1 hairless mice. The skin of the dorsal region was exposed to SLS (5%) for 3 h alone or together with 5% or 10% of glycerol respectively. Further two groups received xylitol solutions (8.26% and 16.52% respectively) using the same osmolarities, which were equivalent to those of the glycerol treatments. The control group was treated with purified water. Transepidermal water loss (TEWL) and skin hydration were determined. Microcirculatory parameters of inflammation were observed by means of intravital videomicroscopy (IVM). Furthermore, accumulation of neutrophil granulocytes and lymphocytes, the expression of inflammatory cytokines and SLS penetration were assessed, as well. Treatment with the 10% of glycerol and both concentrations of xylitol inhibited the SLS-induced elevation of TEWL and moderated the irritant-induced increase in dermal blood flow and in the number of leucocyte-endothelial interactions. All concentrations of the applied polyols improved hydration and prevented the accumulation of lymphocytes near the treatment site. At the mRNA level, neither glycerol nor xylitol influenced the expression of interleukin-1 alpha. However, expression of interleukin-1 beta was significantly decreased by the 10% glycerol treatment, while expression of tumour necrosis factor-alpha decreased upon the same treatment, as well as in response to xylitol. Higher polyol treatments decreased the SLS penetration to the deeper layers of the stratum corneum. Both of the analysed polyols exert considerable anti-irritant and anti-inflammatory properties, but the effective concentration of xylitol is lower than that of

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCETM

PubMed Central

Jang, Won-hee; Jung, Kyoung-mi; Yang, Hye-ri; Lee, Miri; Jung, Haeng-Sun; Lee, Su-Hyon; Park, Miyoung; Lim, Kyung-Min

2015-01-01

The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCETM which is reconstructed with non-transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCETM can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines. PMID:26157556

Skin care and incontinence

MedlinePlus

... skin problems such as redness, peeling, irritation, and yeast infections likely. Bedsores ( pressure sores ) may also develop ... drying the skin. Incontinence problems can cause a yeast infection on the skin. This is an itchy, ...

Zebrafish Locomotor Responses Predict Irritant Potential of ...

EPA Pesticide Factsheets

Over the past few decades, the drying and warming trends of global climate change have increased wildland fire (WF) season length, as well as geographic area impacted. Consequently, exposures to WF fine particulate matter (PM2.5; aerodynamic diameter <2.5 µm) are likely to increase in frequency and duration, contributing to a growing public health burden. Given the influence of fuel type and combustion conditions on WFPM2.5 composition, there is pressing need to identify the biomass fuel sources and emission constituents that drive toxicity. Previously, we reported the utility of 6-day post-fertilization (dpf) zebrafish larvae in evaluating diesel exhaust PM-induced irritation, demonstrating responses analogous to those in mammals. In the present study, combustions, separated by smoldering or flaming conditions, of pine needles, red oak, pine, eucalyptus, and peat were achieved using an automated tube furnace paired with a cryo-trapping apparatus to collect condensates of emissions. The condensates were extracted and prepared for use in zebrafish assays. We hypothesized that 1) the extractable organic fractions of biomass smoke PM will elicit dose-dependent irritant responses in 6-dpf zebrafish larvae, and 2) the relative potencies will vary across biomass emissions, potentially driven by varying chemical composition of fuel sources. Six-dpf zebrafish (n= 28-32/group) were exposed acutely to PM extracts (5 concentrations; 0.3-30 µg/ml; half-log intervals) and

Self-perceived sensory responses to soap and synthetic detergent bars correlate with clinical signs of irritation.

PubMed

Simion, F A; Rhein, L D; Morrison, B M; Scala, D D; Salko, D M; Kligman, A M; Grove, G L

1995-02-01

Epidemiologic studies indicate that after using soaps and other personal care products, many consumers experience irritation. In 50% of the cases the feelings of skin dryness, itching, and stinging occur in the absence of visible signs of irritation. We sought to determine the relation between self-perceived sensory responses of panelists to cleansing products and clinical signs of irritation. A combination of exaggerated arm-washing methods was designed to induce clinical signs of irritation with psychometric techniques developed to quantify sensations. Two studies demonstrated that panelists could reproducibly differentiate between products on the basis of the sensations they felt and that there was a significant correlation (frequently r > 0.80) between these and the observable signs. In the case of skin dryness panelists differentiated products several washing cycles before observable differences were detected. Sensory evaluations of irritation yield additional information on soap and detergent irritancy beyond clinical observations and expand understanding of the irritation process.

Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%.

PubMed

Colón, Luz E; Johnson, Lori A; Gottschalk, Ronald W

2007-04-01

Topical therapy for rosacea aims to reduce inflammatory lesions and decrease erythema but can carry side effects such as stinging, pruritus, and burning. Metronidazole and azelaic acid gel 15% are U.S. Food and Drug Administration-approved for the treatment of rosacea. The current study was conducted to assess the cumulative irritation potential of 2 formulations of metronidazole 0.75% gel and 1% gel--and azelaic acid gel 15% over 21 days (N=36). Results of this study demonstrated a significantly greater poten tial for irritation from azelaic acid compared with metronidazole gel 0.75% (P < .0001), which had significantly greater potential for irritation compared with metronidazole gel 1% (P = .0054). Metronidazole gel 1% had a similar profile to white petrolatum.

Effects of topical corticosteroid and tacrolimus on ceramides and irritancy to sodium lauryl sulphate in healthy skin.

PubMed

Jungersted, Jakob Mutanu; Høgh, Julie K; Hellegren, Lars I; Jemec, Gregor B E; Agner, Tove

2011-05-01

The skin barrier, located in the stratum corneum, is influenced mainly by the lipid and protein composition of this layer. In eczematous diseases impairment of the skin barrier is thought to be of prime importance. Topical anti-inflammatory drugs and emollients are the most widely used eczema treatments. The aim of this study was to examine the effects of topically applied corticosteroid, tacrolimus and emollient on stratum corneum lipids and barrier parameters. Nineteen healthy volunteers participated in the study. Both forearms of the subjects were divided into four areas, which were treated twice daily for one week with betamethasone, tacrolimus, emollient, or left untreated, respectively. After one week each area was challenged with a 24 h sodium lauryl sulphate patch test. The lipids were collected using the cyanoacrylate method and evaluated by high performance thin layer chromatography. For evaluation of the skin barrier, transepidermal water loss, erythema and electrical capacitance were measured. The ceramide/cholesterol ratio was increased in betamethasone- (p = 0.008) and tacrolimus-treated (p = 0.025) skin compared with emollient-treated skin. No differences in ceramide subgroups were found between treatment regimes. Pretreatment with betamethasone (p = 0.01) or with tacrolimus (p = 0.001) causes a decreased inflammatory response to sodium lauryl sulphate compared with emollient. In conclusion, treatment with betamethasone and tacrolimus has a positive effect on the ceramide/cholesterol ratio and susceptibility to irritant reaction compared with an emollient.

Occupational allergic and irritant contact dermatitis in workers exposed to polyurethane foam.

PubMed

Kieć-Świerczyńska, Marta; Swierczyńska-Machura, Dominika; Chomiczewska-Skóra, Dorota; Nowakowska-Świrta, Ewa; Kręcisz, Beata

2014-04-01

To evaluate sensitization to chemicals present in work environment after an outbreak of contact dermatitis in workers of vehicle equipment factory, exposed to polyurethane foam, based on 4,4'-diphenylmethane diisocyanate (MDI). From among 300 employees, 21 individuals reporting work-related skin and/or respiratory tract symptoms underwent clinical examination, patch testing, skin prick tests, spirometry and MDI sIgE measurement in serum. Patch tests included isocyanates series, selected rubber additives, metals, fragrances, preservatives, and an antiadhesive agent. Clinical examination revealed current eczema in the area of hands and/or forearms in 10 workers. Positive patch test reactions were found in 10 individuals, the most frequent to diaminodiphenylmethane and 4-phenylenediamine (7 persons). Reactions to an antiadhesive agent were assessed as irritant (5 workers). Except for sensitization to common aeroallergens, no significant abnormalities were found in the remaining tests. Occupational allergic contact dermatitis was diagnosed in 7 workers, irritant contact dermatitis in 10 and coexisiting allergic and irritant contact dermatitis in 3 workers. In workers manufacturing products from polyurethane foam, attention should be paid to the risk of developing contact dermatitis. Skin problems in our study group were attributable probably to insufficient protection of the skin.

A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target

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

Akram, Muhammad

Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC{sub 50} for NO inhibition in macrophages: 4.61 μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPDmore » 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation. - Highlights: • An anti-inflammatory flavonoid CPD 14 was newly synthesized from macakurzin C. • CPD 14 potently inhibited inflammatory reaction in keratinocytes and macrophages. • Dermal toxicity by irritation or sensitization in rats was protected by CPD 14. • Attenuated NF-κB and activated Nrf2/HO-1 were main mechanisms of CPD 14 action.« less

Taxanes: vesicants, irritants, or just irritating?

PubMed

Barbee, Meagan S; Owonikoko, Taofeek K; Harvey, R Donald

2014-01-01

Several classes of antineoplastic agents are universally referred to as vesicants with ample supporting literature. However, the literature surrounding the taxanes is controversial. While the American Society of Clinical Oncology and Oncology Nursing Society Chemotherapy Administration Safety Standards and the Chemotherapy and Biotherapy Guidelines and Recommendations for Practice identify the risks of extravasation and the parameters surrounding the infusion of known vesicants, recommend administration sites for known agents, and recommend antidotes for particular extravasation cases, they fail to provide specific recommendations for the administration of individual taxanes, or a classification system for antineoplastic agents as vesicants, irritants, or inert compounds. There is also a lack of prescribing information regarding such recommendations. The lack of a formal classification system further complicates the accurate delineation of vesicant antineoplastic agents and subsequent appropriate intravenous administration and extravasation management. There are several factors that make the classification of taxanes as vesicants or irritants challenging. Comprehensive preclinical data describing potential mechanisms of tissue damage or vesicant-like properties are lacking. Furthermore, most case reports of taxane extravasation fail to include the parameters surrounding administration, such as the concentration of medication and duration of infusion, making it difficult to set parameters for vesicant potential. Subsequently, many practitioners default to central venous administration of taxanes without evidence that such administration minimizes the risk of extravasation or improves outcomes thereof. Here, we review briefly the data surrounding taxane extravasation and potential vesicant or irritant properties, classify the taxanes, and propose a spectrum for antineoplastic agent potential to cause tissue injury that warrants clinical intervention if extravasation

Proteomic Analysis of the Human Skin Proteome after In Vivo Treatment with Sodium Dodecyl Sulphate

PubMed Central

Parkinson, Erika; Skipp, Paul; Aleksic, Maja; Garrow, Andrew; Dadd, Tony; Hughes, Michael; Clough, Geraldine; O′Connor, C. David

2014-01-01

Background Skin has a variety of functions that are incompletely understood at the molecular level. As the most accessible tissue in the body it often reveals the first signs of inflammation or infection and also represents a potentially valuable source of biomarkers for several diseases. In this study we surveyed the skin proteome qualitatively using gel electrophoresis, liquid chromatography tandem mass spectrometry (GeLC-MS/MS) and quantitatively using an isobaric tagging strategy (iTRAQ) to characterise the response of human skin following exposure to sodium dodecyl sulphate (SDS). Results A total of 653 skin proteins were assigned, 159 of which were identified using GeLC-MS/MS and 616 using iTRAQ, representing the most comprehensive proteomic study in human skin tissue. Statistical analysis of the available iTRAQ data did not reveal any significant differences in the measured skin proteome after 4 hours exposure to the model irritant SDS. Conclusions This study represents the first step in defining the critical response to an irritant at the level of the proteome and provides a valuable resource for further studies at the later stages of irritant exposure. PMID:24849295

Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity

PubMed Central

Yin, Shijin; Luo, Jialie; Qian, Aihua; Du, Junhui; Yang, Qing; Zhou, Shentai; Yu, Weihua; Du, Guangwei; Clark, Richard B.; Walters, Edgar T.; Carlton, Susan M.; Hu, Hongzhen

2013-01-01

Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity. PMID:23925292

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

PubMed

Nisbet, Stephanie

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

Novel isotretinoin microemulsion-based gel for targeted topical therapy of acne: formulation consideration, skin retention and skin irritation studies

NASA Astrophysics Data System (ADS)

Patel, Mrunali R.; Patel, Rashmin B.; Parikh, Jolly R.; Patel, Bharat G.

2016-04-01

Isotretinoin was formulated in novel microemulsion-based gel formulation with the aim of improving its solubility, skin tolerability, therapeutic efficacy, skin-targeting efficiency and patient compliance. Microemulsion was formulated by the spontaneous microemulsification method using 8 % isopropyl myristate, 24 % Labrasol, 8 % plurol oleique and 60 % water as an external phase. All plain and isotretinoin-loaded microemulsions were clear and showed physicochemical parameters for the desired topical delivery and stability. The permeation profiles of isotretinoin through rat skin from selected microemulsion formulation followed zero-order kinetics. Microemulsion-based gel was prepared by incorporating Carbopol®971 in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of isotretinoin, indicating its potential in improving topical delivery of isotretinoin. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of isotretinoin in the treatment of acne.

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

PubMed

Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

2018-01-01

Ibuprofen is a commonly used non-steroidal anti-inflammatory drug administered to treat injuries, joint pain, and recurrent muscular skeletal pain. The aim of this study was to determine the cutaneous irritancy of a medicated ibuprofen plaster compared with a placebo plaster in healthy volunteers. Healthy volunteers (N = 31) were treated at the same time with one ibuprofen and one placebo plaster. The ibuprofen and placebo plaster were applied in a randomized fashion to sites on the left or right side of subjects' lower backs. At each scheduled visit, the plasters and applications sites were assessed for degree of adhesion and skin irritancy, respectively. The plasters were applied on study Days 1, 2, 3, 5, 8, 10, 12, 15, 17, and 19, with final plaster removal on Day 22. The ibuprofen medicated plaster compared with placebo had a lower percentage of Grade 1 (23.3% vs. 46.7%, respectively), Grade 2 (10% vs. 20%), and ≥Grade 3 (3% vs. 16.1%) irritancy scores after 21 days of application. The mean irritation score across the study was 0.40 for the ibuprofen medicated plaster and 1.18 for the placebo plaster. The irritation score on Day 22 of the study was 0.53 for the ibuprofen medicated plaster and 1.50 for placebo. The placebo plaster was associated with a higher number of stopped applications due to Grade 3 or above skin reactions compared with the ibuprofen medicated plaster (5 vs. 1, respectively). The ibuprofen medicated plaster was well tolerated and was associated with lower irritancy than the placebo plaster.

The Yucatan miniature swine as an in vivo model for screening skin depigmentation.

PubMed

Nair, X; Tramposch, K M

1991-12-01

The usefulness of the Yucatan miniature pig as a screen for skin dipigmenting activity by topical application was evaluated with standard compounds. This is a naturally occurring breed of swine with light brown to dark brown skin that is relatively hairless. The skin morphology, including the pattern of pigment distribution, in this breed of swine closely resembles the human skin. Test compounds examined in this study included the three standard compounds with known clinical depigmenting activity, hydroquinone (HQ), 4-hydroxyanisole (4HA) and tert-butyl catechol (TBC), each at a 5% concentration. Test materials in 25 microliters of propylene glycol/ethanol (50:50) were applied topically twice daily, 7 days a week for 90 days to test sites on each side of the dorsal mid-line. Test sites were graded weekly for variation in pigmentation and local irritation. After 90 days of test material application, skin biopsies of the test sites were taken for histological evaluation. Topical application of HQ, 4HA and TBC promoted marked skin depigmentation which was substantiated by reductions of pigment and melanocytes observed on microscopic examination. While both HQ and TBC produced marked local irritation, 4HA was only mildly irritating. These results suggest that the Yucatan pig, could be a potentially useful model for screening compounds with skin depigmenting activity.

A new cell-based method for assessing the eye irritation potential of chemicals: an alternative to the Draize test.

PubMed

Cho, Sun-A; An, Susun; Lee, Eunyoung; Shin, Kyeho; Cho, Jun-Cheol; Lee, Tae Ryong

2012-07-20

Using a human corneal cell line (HCE-T cells) and 2 evaluation criteria, we developed a new alternative method to assess the eye irritation potential of chemicals. We exposed HCE-T cells to different concentrations of 38 chemicals for 1h and measured relative cell viability (RCV) as an endpoint at each concentration. Using the RCV values, we calculated the RCV50. We also exposed HCE-T cells to 3 fixed concentrations of the 38 chemicals (5%, 0.5%, and 0.05%) for 1h and measured the RCV at each concentration. Using the RCV values at 5%, 0.5%, and 0.05%, we developed a new criterion for eye irritation potential (total eye irritation score, TEIS) and estimated the ocular irritancy. We then assessed the correlation of the results of RCV50 and TEIS with those of the Draize rabbit eye irritation. Both the RCV50 and TEIS results exhibited good positive correlations (sensitivity: 80.77%, specificity: 83.33%, and accuracy: 81.58% for TEIS; sensitivity: 73.08-76.92%, specificity: 75.00%, and accuracy: 73.68-76.32% for RCV50). We conclude that the new in vitro model using HCE-T cells is a good alternative evaluation model for the prediction of the eye irritation potential of chemicals. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Infant Skin Care Products: What Are the Issues?

PubMed

Kuller, Joanne McManus

2016-10-01

Infant skin is susceptible to dryness and irritation from external factors, including topical skin care products not formulated for the infant's skin. This may increase the risk of contact dermatitis. Parents frequently express concern regarding potential harm from ingredients in skin care products and seek information. This is complicated by several skin care myths. The purpose of this literature review was to provide evidence-based information to educate parents on the use of products for preterm and term infants. Multiple searches using PubMed were conducted including the search terms "infant skin care," "infant products," "infant bath," "emollients," "diaper skin care," and "diaper wipes." Reference lists of comprehensive reviews were also scanned. Google searches were used to assess consumer information, product information, and regulatory guidelines. There is little scientific evidence to support safety of natural/organic products on infant skin. Raw materials originate from different sources, complicating testing and comparisons of ingredients. Research shows that cleansers formulated for infant skin do not weaken the skin barrier the way harsher soaps and detergents can. Oils with the lowest oleic acid content provide a lower risk of irritant contact dermatitis. Nurses must be informed about natural and organic products, preservatives, and fragrances and know the definition of commonly used marketing terms. Decisions regarding the use of infant products in preterm and term infants should be evidence based. More research is needed to support claims regarding the safety of products used on infant skin.

A study of the human skin-whitening effects of resveratryl triacetate.

PubMed

Ryu, Ja Hyun; Seok, Jin Kyung; An, Sang Mi; Baek, Ji Hwoon; Koh, Jae Sook; Boo, Yong Chool

2015-04-01

Resveratrol has a variety of bioactivities that include its anti-melanogenic effects, but its use in cosmetics has been challenging partly because of its chemical instability. Resveratryl triacetate (RTA) is a prodrug that can enhance stability. The purpose of this study was to examine the skin safety and whitening effects of RTA in human subjects. The primary skin irritation potentials of RTA and resveratrol were tested at 0.1 and 0.5 % on human subjects. Resveratrol at a concentration of 0.5 % induced weak skin irritation, whereas RTA did not induce any skin responses. The skin-whitening efficacy of a cosmetic formulation containing 0.4 % RTA was evaluated in two different test models. In the artificial tanning model, the test product and the control product were applied twice daily to the skin of the forearms of 22 human subjects after pigmentation induction by ultraviolet irradiation. Applying the test and the control products to the artificial tanning model for 8 weeks increased the individual topology angles (ITA°) by 17.06 and 13.81 %, respectively, a difference that was statistically significant (p < 0.05). In the hyperpigmentation model, the test product and the control product were applied twice daily to the faces of 21 human subjects. The averaged intensity of the hyperpigmented spots decreased by 2.67 % in the test group and 1.46 % in the control group, a difference that was statistically significant (p < 0.05). Therefore, RTA incorporated into cosmetic formulations can whiten human skin without inducing skin irritation.

The use of different concentrations of betaine as a reducing irritation agent in soaps monitored visually and non-invasively.

PubMed

Nicander, Ingrid; Aberg, Peter; Ollmar, Stig

2003-02-01

Products containing detergents can damage the skin and give rise to irritant contact dermatitis. Therefore, attempts have been made to find less irritating detergents as well as substances decreasing undesired side-effects of detergents, and a novel approach is offered by betaine. The aim of the study has been to determine the irritating properties of some liquid soaps for personal hygiene and to map the effect of different concentrations of betaine using electrical impedance, trans-epidermal water loss and visual inspection. Twenty-eight healthy subjects were patch tested with different commercial soaps with and without betaine and sodium lauryl sulphate on both volar forearms for 24 h. A site with distilled water and an unoccluded area were used as references. Responses of the skin reactions were evaluated by visual inspection and by measuring trans-epidermal water loss and electrical impedance before application and 24 h after removal of the chambers. Significant skin reactions were found for all soaps tested but the soaps containing betaine were the least irritating. However, the skin irritation did not decrease with increasing concentrations of betaine in the tested range. On the whole the differences between the products were not large. The non-invasive methods used were more sensitive than visual assessment for evaluation of invisible or barely visible skin responses. Copyright Blackwell Munksgaard 2003

Evaluation of ocular irritancy of coal-tar dyes used in cosmetics employing reconstructed human cornea-like epithelium and short time exposure tests.

PubMed

Lee, Miri; Nam, Ki Taek; Kim, Jungah; Lim, Song E; Yeon, Sang Hyeon; Lee, Buhyun; Lee, Joo Young; Lim, Kyung-Min

2017-10-01

Coal-tar dyes in cosmetics may elicit adverse effects in the skin and eyes. Countries, like the US, have banned the use of coal-tar dyes in cosmetics for the eye area due to the potential for ocular irritation. We evaluated the eye irritation potential of 15 coal-tar dyes permitted as cosmetic ingredients in reconstructed human cornea-like epithelium (RhCEs [EpiOcular™ and MCTT HCE™]) tests and the short time exposure (STE) test. Eosin YS, phloxine B, tetrachlorotetrabromofluorescein, and tetrabromofluorescein were identified as irritants in RhCEs; dibromofluorescein and uranine yielded discrepant results. STE enabled further classification in accordance with the UN Globally Harmonized System of Classification and Labelling of Chemicals, as follows: eosin YS as Cat 2; phloxine B, Cat 1; and tetrachlorotetrabromofluorescein and tetrabromofluorescein, Cat 1/2. STE indicated dibromofluorescein (irritant in EpiOcular™) and uranine (irritant in MCTT HCE™) as No Cat, resulting in the classification of "No prediction can be made." based on bottom-up approach with each model. These results demonstrated that in vitro eye irritation tests can be utilized to evaluate the potential ocular irritancy of cosmetic ingredients and provide significant evidence with which to determine whether precautions should be given for the use of coal-tar dyes in cosmetics or other substances applied to the eye area. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of skin barrier in occupational contact dermatitis.

PubMed

Jakasa, Ivone; Thyssen, Jacob P; Kezic, Sanja

2018-06-12

Skin diseases represent one of the most common work-related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis, which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier is different. In ICD, perturbation of the skin barrier is the primary event which sets into motion diverse metabolic processes and triggers activation of innate immunity without involvement of adaptive immune system. In ACD, a type IV hypersensitivity reaction induced by contact allergens, the skin barrier impairment may evoke innate signaling pathways during the sensitization phase required for the activation of T-cell adaptive response. Thus, skin barrier impairment may increase the risk of ICD or ACD not only because of enhanced permeability and ingress of irritants and allergens, but also by generation of innate immune signal needed for the induction of allergic response. Hence, an efficient way to prevent CD is to avoid skin barrier damage in the workplace. This review focuses on the skin barrier, how it is affected by skin irritants and how its impairment contributes to development of ICD and ACD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The use of a measure of acute irritation to predict the outcome of repeated usage of hand soap products.

PubMed

Williams, C; Wilkinson, M; McShane, P; Pennington, D; Fernandez, C; Pierce, S

2011-06-01

Healthcare-associated infection is an important worldwide problem that could be reduced by better hand hygiene practice. However, an increasing number of healthcare workers are experiencing irritant contact dermatitis of the hands as a result of repeated hand washing. This may lead to a reduced level of compliance with regard to hand hygiene. To assess whether a measure of acute irritation by hand soaps could predict the effects of repeated usage over a 2-week period. In a double-blind, randomized comparison study, the comparative irritation potential of four different hand soaps was assessed over a 24-h treatment period. The effect of repeated hand washing with the hand soap products over a 2-week period in healthy adult volunteers on skin barrier function was then determined by assessment of transepidermal water loss (TEWL), epidermal hydration and a visual assessment using the Hand Eczema Severity Index (HECSI) at days 0, 7 and 14. A total of 121 subjects from the 123 recruited completed phase 1 of the study. All four products were seen to be significantly different from each other in terms of the irritant reaction observed and all products resulted in a significantly higher irritation compared with the no-treatment control. Seventy-nine of the initial 121 subjects were then enrolled into the repeated usage study. A statistically significant worsening of the clinical condition of the skin as measured by HECSI was seen from baseline to day 14 in those subjects repeatedly washing their hands with two of the four soap products (products C and D) with P-values of 0·02 and 0·01, respectively. Subclinical assessment of the skin barrier function by measuring epidermal hydration was significantly increased from baseline to day 7 after repeated hand washing with products A, B and D but overall no significant change was seen in all four products tested by day 14. A statistically significant increase in TEWL at day 14 was seen for product A (P = 0·02) indicating a

Mammalian Toxicity of Munition Compounds. Phase 1. Acute Oral Toxicity Primary Skin and Eye Irritation, Dermal Sensitization, and Disposition and Metabolism

DTIC Science & Technology

1975-07-22

Mononitroglycerins Nitrocellulose White Phosphor 20. ABSTRACT (C^nllnu eery and Identify by block number) 0D | jSJ’TJ M73 EDITION OF I NOV 6» IS...White Phosphorus 2. Synthesis of DNGs and MNGs 3. Analysis of Chemicals . C. Acute LD D. Primary Skin and Eye Irritation E. Dermal...by the Radford Army Ammunition Plant (Radford, Virginia). 2. Synthesis of DNGs and MNGs a. 1,2-DNG: to that of Dunstan et al.— The sample was

Rat epidermal keratinocyte organotypic culture (ROC) compared to human cadaver skin: the effect of skin permeation enhancers.

PubMed

Pappinen, Sari; Tikkinen, Sanna; Pasonen-Seppänen, Sanna; Murtomäki, Lasse; Suhonen, Marjukka; Urtti, Arto

2007-03-01

The objective of this study was to evaluate the response of the rat epidermal keratinocyte organotypic culture (ROC) to permeation enhancers, and to compare these responses to those in human cadaver skin. Different concentrations of two mixtures for enhancing permeation were investigated, sodium dodecyl sulfate:phenyl piperazine and methyl pyrrolidone:dodecyl pyridinium chloride, using skin impedance spectroscopy and two experimental compounds, the lipophilic corticosterone and the hydrophilic sucrose. The chemical irritation effects of the formulations were evaluated based on leakage of lactate dehydrogenase enzyme (LDH) and cellular morphological perturbation. This study provides evidence for direct correlations of permeation/permeation, impedance/impedance and permation/impedance between the culture model and human skin. The only exception was the enhancer induced permeation of sucrose which was 1-40-fold higher in ROC compared to human skin, reflecting the more disordered lipid organization in stratum corneum and consequently the greater number of polar pathways. LDH leakage and cellular morphology indicated that it was possible to differentiate between safe permeation enhancers from irritating agents. This is not only the first study to have compared the enhancer effects on a cultured skin model with human skin, but also it has demonstrated enhancer induced irritation using an artificial skin model.

Profile of irritant patch testing with detergents: sodium lauryl sulfate, sodium laureth sulfate and alkyl polyglucoside.

PubMed

Löffler, H; Happle, R

2003-01-01

The cutaneous reaction to detergents follows distinct kinetic rules: the duration of application and the irritant concentration are of major importance. The aim of this study was to evaluate the differences in kinetics of skin reaction between the standard irritant sodium lauryl sulfate (SLS), and 2 modern detergents: sodium laureth sulfate (SLES) and alkyl polyglucoside (APG). We performed patch testing with SLS and SLES (or APG) at different concentrations (0.125, 0.25, 0.5, 1.0 and 2.0%) and with different exposure times (6, 12 and 24 h). Evaluation was conducted by measurement of transepidermal water loss (TEWL) and laser Doppler flowmetry (LD) 24 h, 7 and 10 days after patch removal. We found a pronounced reaction to SLS, and a far milder one to SLES. Even at the highest concentration the skin reaction to APG was hard to detect. During the regeneration period (day 3-10) SLS showed even at day 10 an increased TEWL at all concentrations tested. The irritation due to SLES was convincingly detectable only up to day 7, whereas the APG-tested skin areas showed no significant reaction even at day 3. These results demonstrate the improvement in reduction of skin irritation achieved by development of novel detergents.

Use of potentially harmful skin-lightening products among immigrant women in Rome, Italy: a pilot study.

PubMed

Cristaudo, A; D'Ilio, S; Gallinella, B; Mosca, A; Majorani, C; Violante, N; Senofonte, O; Morrone, A; Petrucci, F

2013-01-01

Skin-lightening products are increasingly common in European cities. These products may contain substances that are banned under EU regulations as they can induce adverse effects, including cutaneous and systemic reactions (e.g., mercury, hydroquinone and topical corticosteroids). To assess the knowledge, attitudes and practices of women regarding skin-lightening products and to quantify the potentially harmful substances in the products used. We performed a cross-sectional study among 82 non-Italian women visiting an outpatient facility in Rome, Italy. The women completed a questionnaire on product use, side effects and risk awareness. We performed patch tests among a subgroup of 48 women who presented with contact dermatitis. We also quantified the allergenic and toxic substances in the 14 products reported, using dynamic reaction cell inductively coupled plasma mass spectrometry for metals and high-performance liquid chromatography for hydroquinone and topical corticosteroids. Out of the 82 women, 33 used skin-lightening products; about one fourth of these women were aware of potential risks. Three cosmetic creams and two soaps contained high concentrations of metals (Cr, Ni and Pb); hydroquinone was found in three creams and one oil. The only topical corticosteroid detected was dexamethasone, in one product. More than half of the women in the clinical evaluation had irritant contact dermatitis (i.e., negative response to patch test). Among immigrant women in Rome, the use of skin-lightening products seems to be fairly common, and some of these products contain potentially hazardous substances. Consumers must be informed of the potential risks, and EU regulations must be more strictly enforced. Copyright © 2013 S. Karger AG, Basel.

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.

The three moments of skin cream application: an evidence-based proposal for use of skin creams in the prevention of irritant contact dermatitis in the workplace.

PubMed

Hines, J; Wilkinson, S M; John, S M; Diepgen, T L; English, J; Rustemeyer, T; Wassilew, S; Kezic, S; Maibach, H I

2017-01-01

Contact dermatitis is one of the most common occupational diseases, with serious impact on quality of life, lost days at work and a condition that may be chronically relapsing. Regular prophylactic skin cream application is widely acknowledged to be an effective prevention strategy against occupational contact dermatitis; however, compliance rates remain low. To present a simple programme for skin cream application in the workplace with focus on implementation to drive down the rate of occupational irritant contact dermatitis, an expert panel of eight international dermatologists combined personal experience with extensive literature review. The recommendations are based on clinical experience as supported by evidence-based data from interventional studies. The authors identified three moments for skin cream application in the work place: (i) before starting a work period; (ii) after washing hands; and (iii) after work. Affecting behaviour change requires systematic communications, monitoring and reporting, which is proposed through Kotter's principles of organizational change management. Measurement tools are provided in the appendix. Interventional data based on application of this proposal is required to demonstrate its effectiveness. © 2016 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride

PubMed Central

Anderson, Stacey E.; Shane, Hillary; Long, Carrie; Lukomska, Ewa; Meade, B. Jean; Marshall, Nikki B.

2016-01-01

Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects. PMID:27216637

Cleansing lotion containing tamarind fruit pulp extract. II. Study of cumulative irritation effects in human.

PubMed

Maenthaisong, Ratree; Viyoch, Jarupa; Chaiyakunapruk, Nathorn; Warnnissorn, Prateep

2007-09-01

Cleansing lotion containing extract of tamarind fruit pulp was developed to provide skin a lighter effect. Skin irritation may occur due to keratolytic effect of alpha-hydroxyl acids (AHA) in the tamarind fruit pulp extract. To assess the cumulative irritation effect of cleansing lotion containing tamarind fruit extract with 2% (w/w) tartaric acid on human skin compared with placebo product and de-ionized water. The study design was a single-blinded, randomized side of arm, and controlled study. Three samples, including test product, placebo product, and de-ionized water, were repeatedly applied on the inner forearm of 15 healthy females (aged 28.3 +/- 3.1 years) for 30 min daily for 5 days under semi-occlusive patch. Skin irritation was measured by using visual scoring and instruments such as Tewameter and Mexameter. All measurements were done before application of samples every day from day 1 until day 5. Final measurements were done after the last application for 3 days (day 8). The results obtained from the visual scoring scale indicated no irritation signs and symptoms of test product. Mean differences of transepidermal water loss and erythema values between test product and de-ionized water and between test and placebo products were not statistically significant (P > 0.05). These findings indicate a preliminary safety evidence of our developed cleansing lotion containing the natural AHAs and can be used as cumulative evidence for supporting the future home use study of this product in human.

Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of "Zapote" Pouteria mammosa (L.) Cronquist.

PubMed

Dutok, Carlos M S; Berenguer-Rivas, Clara Azalea; Rodríguez-Leblanch, Elizabeth; Pérez-Jackson, Liliana; Chil-Nuñez, Idelsy; Escalona-Arranz, Julio César; Reyes-Tur, Bernardo; Queiroz, Margareth M C

2015-01-01

The common use of Pouteria mammosa (L.) Cronquist, "Mamey or Zapote," in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25%) Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD). The aqueous extract was located in the following category: not classified as toxic (CTA 5), while hydroalcoholic extract at 25% was classified as dangerous (CTA 4). Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating.

Differences in Cutaneous Irritation of Five Commonly Used Topical Products.

PubMed

Draelos, Zoe Diana

2016-07-01

Irritation, such as burning and stinging, on the site of application, is a common side effect of topical dermatologic products including creams, lotions, sprays, and foams. This effect may be more pronounced when applying products to atopic or psoriatic skin. The composition of the vehicle may affect the extent of the irritation. This study compared the irritation and erythema potential of 7 different topical dermatologic products to determine the products with the least likelihood of causing discomfort when applied.
Seven sites on the anterior leg of 30 subjects were dry shaven with 10 upward strokes. Subjects rated the stinging of petrolatum (negative control), isopropyl alcohol (positive control), Cetaphil Lotion, triamcinolone 0.1% cream, triamcinolone 0.2% spray, betamethasone foam, and clobetasol 0.05% spray, 1 minute after product application, using a scale of 0 (no symptoms) to 10 (intolerable stinging/burning). The investigator assessed erythema at the sites 30 minutes after application of the products using a scale of 0 (none) to 4 (severe).
Stinging rating score of each product was statistically significant from one another. Petrolatum produced the least stinging (0) and isopropyl alcohol the most (10). Stinging with triamcinolone spray, Cetaphil Lotion, and triamcinolone cream ranked in the lower half of the rating scale (all below 5). Betamethasone foam and clobetal spray ranked the highest at >7. When corrected for the erythema caused by shaving, triamcinolone spray and Cetaphil Lotion produced the least amount of erythema of all the products tested.
Rapid evaporation of the volatile vehicle of triamcinolone spray and the non-irriating nature of the medication left behind may contribute to its low erythema and stinging. This product may be an appropriate choice for patients with compromised skin but who require the advantages and conveniences of a spray vehicle.

J Drugs Dermatol. 2016;15(7):870-873.

Skin Diseases: Questions for Your Health Care Provider

MedlinePlus

Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Questions for Your Health Care Provider Past ... dermatitis worse? What are the most common irritants? Skin cancer What type of skin cancer do I ...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

Scutellaria radix Extract as a Natural UV Protectant for Human Skin.

PubMed

Seok, Jin Kyung; Kwak, Jun Yup; Choi, Go Woon; An, Sang Mi; Kwak, Jae-Hoon; Seo, Hyeong-Ho; Suh, Hwa-Jin; Boo, Yong Chool

2016-03-01

Ultraviolet (UV) radiation induces oxidative injury and inflammation in human skin. Scutellaria radix (SR, the root of Scutellaria baicalensis Georgi) contains flavonoids with high UV absorptivity and antioxidant properties. The purpose of this study was to examine the potential use of SR extract as an additive in cosmetic products for UV protection. SR extract and its butanol (BuOH) fraction strongly absorbed UV radiation and displayed free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radials and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals. They also attenuated the UV-induced death of HaCaT cells. Sunscreen creams, with or without supplementation of SR extract BuOH fraction, were tested in vivo in human trials to evaluate potential skin irritation and determine the sun protection factor (SPF). Both sunscreen creams induced no skin irritation. A sunscreen cream containing 24% ZnO showed an SPF value of 17.8, and it increased to 22.7 when supplemented with 5% SR extract BuOH fraction. This study suggests that SR-derived materials are useful as safe cosmetic additives that provide UV protection. Copyright © 2015 John Wiley & Sons, Ltd.

Wound-Related Allergic/Irritant Contact Dermatitis.

PubMed

Alavi, Afsaneh; Sibbald, R Gary; Ladizinski, Barry; Saraiya, Ami; Lee, Kachiu C; Skotnicki-Grant, Sandy; Maibach, Howard

2016-06-01

To provide information from a literature review about the prevention, recognition, and treatment for contact dermatitis. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Identify signs and symptoms of and diagnostic measures for contact dermatitis.2. Identify causes and risks for contact dermatitis.3. Select appropriate treatment for contact dermatitis and its prevention. Contact dermatitis to wound care products is a common, often neglected problem. A review was conducted to identify articles relevant to contact dermatitis.A PubMed English-language literature review was conducted for appropriate articles published between January 2000 and December 2015.Contact dermatitis is both irritant (80% of cases) or allergic (20% of cases). Frequent use of potential contact allergens and impaired barrier function of the skin can lead to rising sensitization in patients with chronic wounds. Common known allergens to avoid in wound care patients include fragrances, colophony, lanolin, and topical antibiotics.Clinicians should be cognizant of the allergens in wound care products and the potential for sensitization. All medical devices, including wound dressings, adhesives, and bandages, should be labeled with their complete ingredients, and manufacturers should be encouraged to remove common allergens from wound care products, including topical creams, ointments, and dressings.

Tretinoin cyclodextrin complex (RA/CyD) causes less irritation with an equal antiwrinkle effect compared with conventional tretinoin: clinical and histologic studies of photoaged skin.

PubMed

Miura, Tomoe; Takada, Akiyoshi; Ooe, Masahiko

2012-08-01

Topical tretinoin [all-trans-retinoic acid (RA)] currently is widely used to treat photoaged skin. However, undesirable side effects such as erythema, irritation, and scaling are unavoidable and limit the use of tretinoin. To address these issues, the authors developed the tretinoin cyclodextrin complex (RA/CyD), which is tretinoin encapsulated by cyclodextrin. Cyclodextrins are cyclic oligosaccharides commonly used in food additives and fabric fresheners. This study aimed to evaluate the antiwrinkle effect of RA/CyD and alleviation of the side effects compared with RA treatment alone. In this study, 12 photoaged patients completed an 8 week study using RA and RA/CyD in a double-blind manner. Before and after the treatment, the patients' evaluations, wrinkle scores, skin elasticity, and wrinkle area measurement using skin replica were evaluated. Three men were recruited for histologic analysis. The patients reported that undesirable irritant reactions were more moderate with RA/CyD than with RA. In the assessment of wrinkle scores, skin elasticity, and wrinkle area measurement, RA/CyD demonstrated an antiwrinkle effect statistically equal to that of RA. In histology, both RA/CyD and RA demonstrated epidermal hyperplasia. In immunohistochemistry, inflammation induced by RA/CyD was more moderate than that induced by RA. The findings show that RA and RA/CyD result in the equivalent clinical improvement for patients with photoaging. The use of RA/CyD overcomes the drawbacks of RA while possessing equal effect. It is expected that CyD will broaden tretinoin treatment. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Nano vesicular lipid carriers of angiotensin II receptor blocker: Anti-hypertensive and skin toxicity study in focus.

PubMed

Ahad, Abdul; Aqil, Mohd; Kohli, Kanchan; Sultana, Yasmin; Mujeeb, Mohd

2016-05-01

Nanoethosomal carriers of valsartan have been previously prepared, characterized and optimized. A gel formulation of valsartan vesicular lipid carriers was composed of Carbopol(®) (1% w/w), polyethylene glycol-400 (15% w/w) and triethanolamine (0.5% w/w). The influence of the valsartan nanoethosomal formulation developed on the blood pressure of experimental hypertensive rats, and its potential for skin irritation, are presented in this report. The experimental rats were divided into three groups; the control group received no treatment (Group A). Group B was administered methyl prednisolone acetate (20 mg/kg/week) for two weeks (hypertensive control). Group C received methyl prednisolone acetate, followed by administration of the valsartan ethosomal formulation. The blood pressure of the rats was measured using a non-invasive rat blood pressure instrument based on the tail-cuff technique. The statistical analysis was performed using GraphPad InStat 3 software. The treatment group showed a significant (P < 0.05) and constant fall in blood pressure, for up to 48 h. The valsartan ethosomal formulation was found to be effective, with a 34.11% reduction in blood pressure. The formulation's potential for skin irritation was assessed by the Draize irritation score test, which ruled out the possibility of any skin irritation caused by application of the formulation in rats. Our results suggest that nanoethosomes are efficient carriers for transdermal delivery of valsartan, for the management of hypertension.

Using the Slug Mucosal Irritation Assay to Investigate the Tolerability of Tablet Excipients on Human Skin in the Context of the Use of a Nipple Shield Delivery System.

PubMed

Kendall, Richard; Lenoir, Joke; Gerrard, Stephen; Scheuerle, Rebekah L; Slater, Nigel K H; Tuleu, Catherine

2017-04-01

Neonates are particularly challenging to treat. A novel patented drug delivery device containing a rapidly disintegrating tablet held within a modified nipple shield (NSDS) was designed to deliver medication to infants during breastfeeding. However concerns exist around dermatological nipple tolerability with no pharmaceutical safety assessment guidance to study local tissue tolerance of the nipple and the areola. This is the first Slug Mucosal Irritation (SMI) study to evaluate irritancy potential of GRAS excipients commonly used to manufacture rapidly disintegrating immediate release solid oral dosage form METHODS: Zinc sulphate selected as the antidiarrheal model drug that reduces infant mortality, was blended with functional excipients at traditional levels [microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, magnesium stearate]. Slugs were exposed to blends slurried in human breast milk to assess their stinging, itching or burning potential, using objective values such as mucus production to categorize irritation potency RESULTS: Presently an in vivo assay, previously validated for prediction of ocular and nasal irritation, was used as an alternative to vertebrate models to anticipate the potential maternal dermatological tolerability issues to NSDS tablet components. The excipients did not elicit irritancy. However, mild irritancy was observed when zinc sulphate was present in blends. These promising good tolerability results support the continued investigation of these excipients within NSDS rapidly disintegrating tablet formulations. Topical local tolerance effects being almost entirely limited to irritation, the slug assay potentially adds to the existing preformulation toolbox, and may sit in between the in vitro and existing in vivo assays.

Cutaneous tolerability to tretinoin shows little variation with Fitzpatrick skin type.

PubMed

Webster, Guy F

2014-06-01

Determinants of skin irritability are poorly understood. This study aims to assess differences in cutaneous safety/irritation based on Fitzpatrick skin type among patients with acne treated with tretinoin gel microsphere (TGM). This was a phase 4, 12-week, prospective, nonrandomized, open-label, multicenter study. Approximately 500 patients with mild to moderate acne were treated with TGM 0.04% or 0.1% and assessed for cutaneous irritation at baseline and weeks 3, 6, and 12. In this post hoc analysis of patients with Fitzpatrick skin type I-III vs Fitzpatrick skin type IV-VI, there was a general trend toward initial worsening of cutaneous adverse events (AEs) by week 3 across all variables and groups. This was followed by a trend toward improvement and resolution of skin-related AEs from week 3 to week 12 regardless of Fitzpatrick skin type, with a few exceptions. Erythema was the only cutaneous AE that consistently decreased among patients with darker skin. Results from a subsequent 3-group analysis (Fitzpatrick I-II vs Fitzpatrick III-IV vs Fitzpatrick V-VI) generally mirrored those from the 2-group study. Study limitations include patient nonadherence, lack of a placebo arm, and lack of data regarding the impact of concurrent medications on outcomes. There was no correlation between irritation and Fitzpatrick skin type. ABBREVIATIONS USED: adverse event (AE), analysis of variance (ANOVA), benzoyl peroxide (BP), case report form (CRF), modified Global Acne Grading Score (mGAGS), tretinoin gel microsphere (TGM).

Noninvasive measuring methods for the investigation of irritant patch test reactions. A study of patients with hand eczema, atopic dermatitis and controls.

PubMed

Agner, T

1992-01-01

The aim of the study was to assess the susceptibility of clinically normal skin to a standard irritant trauma under varying physiological and patophysiological conditions. Evaluation of skin responses to patch tests with sodium lauryl sulphate (SLS) was used for assessment of skin susceptibility. The following noninvasive measuring methods were used for evaluation of the skin before and after exposure to irritants: measurement of transepidermal water loss by an evaporimeter, measurement of electrical conductance by a hydrometer, measurement of skin blood flow by laser Doppler flowmetry, measurement of skin colour by a colorimeter and measurement of skin thickness by ultrasound A-scan. The studies were carried out on healthy volunteers and patients with eczema. In the first studies the standard irritant patch test for assessment of skin susceptibility was characterized and validated. SLS was chosen among other irritants because of its ability to penetrate and impair the skin barrier. The implications of use of different qualities of SLS was investigated. The applied noninvasive measuring methods were evaluated, and for quantification of SLS-induced skin damage measurement of TEWL was found to be the most sensitive method. Application of the standard test on clinically normal skin under varying physiological and patophysiological conditions lead to the following main results: Seasonal variation in skin susceptibility to SLS was found, with increased susceptibility in winter, when the hydration state of the stratum corneum was also found to be decreased. A variation in skin reactivity to SLS during the menstrual cycle was demonstrated, with an increased skin response at day 1 as compared to days 9-11 in the menstrual cycle. The presence of active eczema distant from the test site increased skin susceptibility to SLS, indicating a generalized hyperreactivity of the skin. Taking these sources of variation into account healthy volunteers and patients with hand eczema and

Dermal safety assessment of Arm & Hammer laundry products formulated for sensitive skin.

PubMed

Frederick, Douglas M; Vorwerk, Linda; Gupta, Archana; Ghassemi, Annahita

2017-09-01

The prevalence of sensitive skin among the general population in industrialized countries is reported to be over 50%. Sensitive skin subjects often report significant reactions to contact with cosmetics, soaps and other consumer products. This paper describes the overall skin compatibility and mildness program for a newly developed, lightly fragranced, colorant free laundry product (i.e. Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent), specially formulated for individuals with sensitive skin. The skin mildness of the product was compared to Arm & Hammer™ Free & Clear liquid laundry detergent with no fragrance or colorant, and an established history of safe use by sensitive skin consumers. The test material was a liquid laundry product with a light scent formulated for sensitive skin consumers (Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent). The product was compared to commercially marketed products for sensitive skin with a history of skin safety in the marketplace, including: a very similar product formulation (Arm & Hammer™ Free & Clear with no fragrance), and several selected competitors' products. Studies were conducted among individuals with self-assessed sensitive skin (based on a questionnaire) using standard protocols for the Human Repeat Insult Patch Test (HRIPT), 10-Day Cumulative Irritation, the Wrist Band Wear test, and the Safety In-Use testing. Responses in all protocols were evaluated by visual scoring of potential dermatologic reactions, and recording any sensory effects at the time of the examination. In addition, sensory effects collected from panelists' daily diaries were also evaluated. The HRIPT confirmed that neither the fragrance alone, nor the product formulation with fragrance, induced contact sensitization in sensitive skin subjects. The 10-Day cumulative irritation study conducted using sensitive skin subjects showed highly favorable skin compatibility, and the test product was comparable to the control

The male beard hair and facial skin - challenges for shaving.

PubMed

Maurer, M; Rietzler, M; Burghardt, R; Siebenhaar, F

2016-06-01

The challenge of shaving is to cut the beard hair as closely as possible to the skin without unwanted effects on the skin. To achieve this requires the understanding of beard hair and male facial skin biology as both, the beard hair and the male facial skin, contribute to the difficulties in obtaining an effective shave without shaving-induced skin irritation. Little information is available on the biology of beard hairs and beard hair follicles. We know that, in beard hairs, the density, thickness, stiffness, as well as the rates of elliptical shape and low emerging angle, are high and highly heterogeneous. All of this makes it challenging to cut it, and shaving techniques commonly employed to overcome these challenges include shaving with increased pressure and multiple stroke shaving, which increase the probability and extent of shaving-induced skin irritation. Several features of male facial skin pose problems to a perfect shave. The male facial skin is heterogeneous in morphology and roughness, and male skin has a tendency to heal slower and to develop hyperinflammatory pigmentation. In addition, many males exhibit sensitive skin, with the face most often affected. Finally, the hair follicle is a sensory organ, and the perifollicular skin is highly responsive to external signals including mechanical and thermal stimulation. Perifollicular skin is rich in vasculature, innervation and cells of the innate and adaptive immune system. This makes perifollicular skin a highly responsive and inflammatory system, especially in individuals with sensitive skin. Activation of this system, by shaving, can result in shaving-induced skin irritation. Techniques commonly employed to avoid shaving-induced skin irritation include shaving with less pressure, pre- and post-shave skin treatment and to stop shaving altogether. Recent advances in shaving technology have addressed some but not all of these issues. A better understanding of beard hairs, beard hair follicles and male

Sensitive skin and stratum corneum reactivity to household cleaning products.

PubMed

Goffin, V; Piérard-Franchimont, C; Piérard, G E

1996-02-01

Products intended for individuals with sensitive skin are being increasingly developed by formulators of household cleaning products. However, there is currently no consensus about the definition and recognition of the biological basis of sensitive skin. We sought to determine the relation between the nature of environmental threat perceived as aggressive by panelists, and the stratum corneum reactivity to household cleaning products as measured by the corneosurfametry test. Results indicate substantial differences in irritancy potential between proprietary products. Corneosurfametry data show significant differences in stratum corneum reactivity between, on the one hand, individuals with either non-sensitive skin or skin sensitive to climate/fabrics, and, on the other hand, individuals with detergent-sensitive skin. It is concluded that sensitive skin is not one single condition. Sound information in rating detergent-sensitive skin may be gained by corneosurfametry.

Irritable Bowel Syndrome

MedlinePlus

... Staying Safe Videos for Educators Search English Español Irritable Bowel Syndrome KidsHealth / For Teens / Irritable Bowel Syndrome What's in ... intestinal disorder called irritable bowel syndrome. What Is Irritable Bowel Syndrome? Irritable bowel syndrome (IBS) is a common intestinal ...

Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

PubMed

Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

2008-03-01

The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

Rates of allergic sensitization and irritation to oxybenzone-containing sunscreen products: a quantitative meta-analysis of 64 exaggerated use studies.

PubMed

Agin, Patricia P; Ruble, Karen; Hermansky, Steven J; McCarthy, Timothy J

2008-08-01

Oxybenzone is an active ingredient found in sunscreen products that absorbs a broad spectrum of ultraviolet (UV) light, with absorbance peaking in the UVB region and extending into the UVA region. Although the overall incidence of sensitization and irritation associated with oxybenzone in the general population remains unclear, a few studies have reported on the incidence in specific circumstances. However, the relevance of these studies to the general population is limited, because the sample populations reported in these papers generally have consisted of individuals who sought medical attention for pre-existing skin conditions. Therefore, the reported incidence of allergic reactions to oxybenzone in these studies may be overestimated as related to the general population. The objective of this meta-analysis was to determine the safety of oxybenzone in participants recruited from the general population. The data from 64 unpublished exaggerated use human repeat insult patch tests (HRIPT) and photoallergy (PA) studies sponsored by Schering-Plough HealthCare Products Inc. between 1992 and 2006 were aggregated and analyzed to evaluate the irritancy and sensitization potential of sunscreen products containing oxybenzone at concentrations between 1% and 6%. Forty-eight of 19 570 possible dermal responses were considered to be suggestive of irritation or sensitization; the mean rate of responses across all formulations was 0.26%. Sensitization rates did not correlate significantly with oxybenzone concentration. The available re-challenge data indicated that only eight of these responses were contact allergies from oxybenzone, and the mean rate of contact allergy to oxybenzone was 0.07%. The source of the skin responses was not confirmed for 15 subjects who were lost to follow-up. However, all subjects were given the opportunity to participate in follow-up testing. Our data indicate that sunscreen products formulated with 1-6% oxybenzone do not possess a significant

Skin Potential as an Indicator of Emotion

ERIC Educational Resources Information Center

Seligman, Linda

1975-01-01

The skin-potential responses of six college students were monitored while each was seen for 10 counseling sessions. Negative skin-potential responses were accompanied by feelings described as pleasant and released; positive responses were associated with unpleasant and inhibited feelings; and neutral responses were often associated with unpleasant…

Celery-based topical repellents as a potential natural alternative for personal protection against mosquitoes.

PubMed

Tuetun, B; Choochote, W; Pongpaibul, Y; Junkum, A; Kanjanapothi, D; Chaithong, U; Jitpakdi, A; Riyong, D; Pitasawat, B

2008-12-01

Celery-based products were investigated for chemical composition, skin irritation, and mosquito repellency in comparison to commercial repellents and the standard chemical, N,N-diethyl-3-methylbenzamide (DEET), with a goal to develop a natural alternative to synthetic repellents for protection against mosquitoes. Chemical identification by gas chromatography coupled with mass spectrometry discovered that the major constituents of Apium graveolens hexane extract (AHE) were 3-n-butyl-tetrahydrophthalide (92.48%), followed by 5.10% beta-selinene and 0.68% gamma-selinene. Evaluation of skin irritation in 27 human volunteers revealed no irritant potential from 25% ethanolic AHE solution. Laboratory investigated repellent against female Aedes aegypti mosquitoes demonstrated that G10 formula, the best AHE-developed product, provided remarkable repellency with a median protection time of 4.5 h (4.5-5 h), which was greater than that of ethanolic DEET solution (25% DEET, 3.5 h) and comparable to that of the best commercial repellent, Insect Block 28 (28.5% DEET, 4.5 h). According to significantly promising results, including highly effective repellency and no potential skin irritation or other side effects, the G10 formula is a worthwhile product that has the promise of being developed for commercialized registration. This developed AHE product could be an acceptable and affordable alternative to conventional synthetic chemicals in preventing mosquito bites, and in turn, helping to interrupt mosquito-borne disease transmission.

Is dermatitis palmaris sicca an irritant contact dermatitis?

PubMed

Chen, Fu-Juan; Liu, Zhen; Zhou, Ying; Chen, Yong-Hua; Fan, Yi-Ming

2013-01-01

Dermatitis palmaris sicca (DPS) is a common dry-fissured palmar dermatitis in Asian women. It may be an irritant contact dermatitis, but the immunophenotype of the cells in its infiltrate is unknown. The aim of this study was to evaluate the role of inflammatory cells in the pathogenesis of DPS. Patch testing was done in 68 patients with DPS, 87 subjects with hand eczema, and 31 healthy subjects. Immunophenotyping of cutaneous inflammatory cells was performed in 8 patients with DPS, 10 subjects with hand eczema, and 8 healthy individuals. Positive patch rates were higher in patients with DPS and those with hand eczema compared with healthy controls, but strong positive (++ or +++) reactions in DPS were fewer compared with hand eczema. Density of CD3, CD4, CD8, and CD68 cells in skin lesions of DPS and hand eczema was significantly higher than that in normal skin. Sparse CD20 cells were present only in hand eczema. Compared with hand eczema, the number of CD3, CD8, CD68, and dermal CD1a cells decreased, but epidermal CD1a cells and CD4/CD8 ratio increased in DPS. The absolute lack of CD20 cells and relative scarcity of dermal CD8 and CD1a cells in skin lesions might be insufficient to induce contact hypersensitivity, so DPS may be an irritant but not allergic contact dermatitis.

Irritancy ranking of 31 cleansers in the Indian market in a 24-h patch test.

PubMed

Lakshmi, C; Srinivas, C R; Anand, C V; Mathew, A C

2008-08-01

Cleansing trends promise freshness, sensory and health benefits but may also be accompanied by an increase in soap-induced skin irritation. The aim of this study was to evaluate the irritant effect of 31 cleansers (28 bar soaps and 3 liquid cleansers) available in the Indian market. Eight percent w/v solutions of the soaps/cleansers were made and 30 microL of each of the solutions were applied to Finn chambers and occluded for 24 h along with distilled water (negative control) and 20% sodium dodecyl sulphate (SDS) as positive control. The sites were graded for erythema and scaling 30 min after removing the patches. The pH of each of the soap solutions was determined. Mean with SD and ANOVA (F-value) was computed separately for each soap/cleanser with respect to the two parameters, erythema and scaling. The total of the means for both the parameters, erythema and scaling was also computed. The cleansers were listed based on this total from the least irritant to the most irritant. The differences between soaps (F-value) was significant for erythema and scaling [erythema = 4.106 (P = 0.000); scaling = 6.006 (P = 0.000)]. Cetaphil cleansing lotion had the lowest erythema score of 0.25. Lowest scaling score of zero was recorded for Cetaphil cleansing lotion and Elovera moisturizing body wash. Aquasoft and Lifebuoy soaps had the highest erythema score of 2.13. Acnex had the highest scaling score of 1.75; Aquasoft, Hamam scrub bath soap and Naturepower sandal soaps were the next with a scaling score of 1.63. Cetaphil cleansing lotion, Aquaderm liquid soap, Dove bar soap and Elovera moisturizing body wash proved to be the least irritant cleansers with a total score of less than 1. The four most irritant soaps/cleansers had an average score of 3.65. The irritant potential of the majority of the cleansers fell between these extremes. The pH of all the soap/cleanser solutions was neutral to alkaline (pH 7-9) except that of Dove bar, Cetaphil cleansing lotion, Aquaderm liquid

Surgery-Related Contact Dermatitis: A Review of Potential Irritants and Allergens.

PubMed

Cook, Kevin A; Kelso, John M

Surgical procedures utilize an increasing number of medical products including antiseptics, anesthetics, gloves, suture materials, tissue adhesives, topical antibiotics, and bandages. Many of these products have irritant potential. Allergic contact dermatitis has also been reported. This review covers preoperative, operative, and postoperative exposures that may result in contact dermatitis. Testing with standard patch panels such as T.R.U.E. Test and the North American Contact Dermatitis Group 65 allergen series does not evaluate for all relevant contactants. A thorough understanding of potential exposures is vital to effectively evaluate a patient with surgery-related contact dermatitis. A systematic approach is needed to ensure that standard patch panels and supplementary patches adequately address each encountered contactant. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The isolated chicken eye test as a suitable in vitro method for determining the eye irritation potential of household cleaning products.

PubMed

Schutte, K; Prinsen, M K; McNamee, P M; Roggeband, R

2009-08-01

Eye irritation is an important endpoint in the safety evaluation of consumer products and their ingredients. Several in vitro methods have been developed and are used by different industry sectors to assess eye irritation. One such in vitro method in use for some time already is the isolated chicken eye test (ICE). This investigation focuses on assessing the ICE as a method to determine the eye irritation potential of household cleaning products, both for product safety assurance prior to marketing and for classification and labeling decisions. The ICE involves a single application of test substances onto the cornea of isolated chicken eyes. Endpoints are corneal swelling, corneal opacity and fluorescein retention. The ICE results were compared to historic LVET data in this study due to availability of such in vivo data and the ability to correlate LVET to human experience data on the outcome of accidental exposures to household cleaning products in general. The results of this study indicate that the ICE test is a useful in vitro method for evaluating the eye irritation/corrosion potential and establishing classification and labeling for household cleaning products. For new product formulations, it is best used as part of a weight-of-evidence approach and benchmarked against data from comparable formulations with known eye irritation/corrosion profiles and market experience.

Interlaboratory study for the assessment of potential irritative properties of hygiene products on the hamster cheek pouch.

PubMed

Bourrinet, P; Conduzorgues, J P; Dutertre, H; Macabies, J; Masson, P; Maurin, J; Mercier, O

1995-02-01

An interlaboratory study was carried out to determine the feasibility and reliability of a method using the hamster cheek pouch as a model for assessing the potential irritative properties of substances intended to be applied to the lips or other mucous membranes. The test substances were applied once daily to both pouches for 14 consecutive days. Local and general tolerances were appraised throughout the study. At the end of the study, histologic examination of the pouches and the main organs was performed. Results of the feasibility study, conducted on various types of commercial products, indicated that this model is suitable for preparations of various consistence and composition. Results of the reliability study, carried out on gel-type preparations containing various concentrations of a known irritant, sodium lauryl sulfate, indicated that the method elicits a dose-dependent reaction for this compound. This hamster cheek pouch method was reproducible for the various parameters under consideration: local tolerance, general tolerance, histologic examination. For all products, results were in good agreement among the various laboratories participating in the study. The French regulatory authorities of the Fraud Repression Department have accepted it as an official method for the evaluation of the potential irritative properties of cosmetics and hygiene products intended to be applied to the lips or other mucous membranes.

Enzymes, detergents and skin: facts and fantasies.

PubMed

Basketter, D A; English, J S C; Wakelin, S H; White, I R

2008-06-01

In their raw state, enzymes of bacterial/fungal origin cause allergic reactions in the lung. Proteolytic enzymes also cause irritation to skin, eyes and the respiratory tract. For 40 years, encapsulated enzymes have been used worldwide in detergent products, especially laundry formulations, and have increasing importance due to biodegradability and functionality at low temperatures, offering environmental benefits. Uniquely to the U.K., for years it has been suggested that the inclusion of enzymes in such products leads to adverse skin reactions, including erythema, pruritus and exacerbation of eczema. In this review, we look at the facts, asking whether there is evidence that the hazards identified for enzymes translate into any risk for consumer health. By considering the actual exposures in consumer use and exaggerated product usage, it is concluded that the irritating and allergenic hazards of enzyme raw materials do not translate into a risk of skin reactions, either irritant or allergic. Investigations of numerous individuals with skin complaints attributed to laundry products demonstrate convincingly that enzymes were not responsible. Indeed, enzyme-containing laundry products have an extensive history of safe use. Thus, the supposed adverse effects of enzymes on skin seem to be a consequence of a mythology. The important practical lesson is that when primary or secondary care practitioners are presented with a skin complaint, it should not be dismissed as a result of using an enzyme-containing laundry product as the diagnosis will certainly lie elsewhere. Education for healthcare professionals could usefully be enhanced to take this on board.

Povidone-iodine induced post-surgical irritant contact dermatitis localized outside of the surgical incision area. Report of 27 cases and a literature review.

PubMed

Borrego, Leopoldo; Hernández, Noelia; Hernández, Zaida; Peñate, Yeray

2016-05-01

Povidone-iodine solution is an antiseptic that is used worldwide as surgical paint and is considered to have a low irritant potential. Post-surgical severe irritant dermatitis has been described after the misuse of this antiseptic in the surgical setting. Between January 2011 and June 2013, 27 consecutive patients with post-surgical contact dermatitis localized outside of the surgical incision area were evaluated. Thirteen patients were also available for patch testing. All patients developed dermatitis the day after the surgical procedure. Povidone-iodine solution was the only liquid in contact with the skin of our patients. Most typical lesions were distributed in a double lumbar parallel pattern, but they were also found in a random pattern or in areas where a protective pad or an occlusive medical device was glued to the skin. The patch test results with povidone-iodine were negative. Povidone-iodine-induced post-surgical dermatitis may be a severe complication after prolonged surgical procedures. As stated in the literature and based on the observation that povidone-iodine-induced contact irritant dermatitis occurred in areas of pooling or occlusion, we speculate that povidone-iodine together with occlusion were the causes of the dermatitis epidemic that occurred in our surgical setting. Povidone-iodine dermatitis is a problem that is easily preventable through the implementation of minimal routine changes to adequately dry the solution in contact with the skin. © 2015 The International Society of Dermatology.

Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants.

PubMed

Barrow, C S; Alarie, Y; Stock, M F

1978-01-01

A decrease in respiratory rate in mice during exposure to irritating airborne chemicals has been utilized as a response parameter to characterize the degree of upper respiratory tract irritation (sensory irritation) to the thermal decomposition products of various polymers. These included polystyrene, polyvinyl chloride, flexible polyurethane foam, polytetrafluorethylene, a fiber glass reinforced polyester resin, and Douglas Fir. Each of the materials was thermally decomposed in a low-mass vertical furnace in an air atmosphere at a programmed heating rate of 20 degrees C/min. Mice, in groups of four, were exposed to graded concentrations of the thermal decomposition products of each of the above materials. Dose-response curves were obtained by utilizing the maximum percent decrease in respiratory rate as the response parameter during each exposure. Comparison of these dose-response curves with other sensory irritants such as chlorine, ammonia, hydrogen chloride, sulfur dioxide, and toluene diisocyanate gave an indication of the sensory irrtation potential of the thermal decomposition products of these various polymers versus that of well-known single airborne chemical irritants. Total stress and incapacitation of the organism during exposure to sensory irritants such as from the thermal decomposition products of synthetic polymers is discussed.

Standardization of skin cleansing in vivo: part I. Development of an Automated Cleansing Device (ACiD).

PubMed

Sonsmann, F K; Strunk, M; Gediga, K; John, C; Schliemann, S; Seyfarth, F; Elsner, P; Diepgen, T L; Kutz, G; John, S M

2014-05-01

To date, there are no legally binding requirements concerning product testing in cosmetics. This leads to various manufacturer-specific test methods and absent transparent information on skin cleansing products. A standardized in vivo test procedure for assessment of cleansing efficacy and corresponding barrier impairment by the cleaning process is needed, especially in the occupational context where repeated hand washing procedures may be performed at short intervals. For the standardization of the cleansing procedure, an Automated Cleansing Device (ACiD) was designed and evaluated. Different smooth washing surfaces of the equipment for ACiD (incl. goat hair, felt, felt covered with nitrile caps) were evaluated regarding their skin compatibility. ACiD allows an automated, fully standardized skin washing procedure. Felt covered with nitrile as washing surface of the rotating washing units leads to a homogenous cleansing result and does not cause detectable skin irritation, neither clinically nor as assessed by skin bioengineering methods (transepidermal water loss, chromametry). Automated Cleansing Device may be useful for standardized evaluation of the cleansing effectiveness and parallel assessment of the corresponding irritancy potential of industrial skin cleansers. This will allow objectifying efficacy and safety of industrial skin cleansers, thus enabling market transparency and facilitating rational choice of products. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CON4EI: Development of serious eye damage and eye irritation testing strategies with respect to the requirements of the UN GHS/EU CLP hazard categories.

PubMed

Verstraelen, Sandra; Van Rompay, An R

2018-06-01

The main objective of the CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project (2015-2016) was to develop tiered, non-animal testing strategies for serious eye damage and eye irritation assessment in relation to the most important drivers of classification. The serious eye damage and eye irritation potential of a set of 80 chemicals was identified based on existing in vivo Draize eye test data and testing was conducted using the following eight alternative test methods: BCOP (Bovine Corneal Opacity and Permeability)+histopathology, BCOP-LLBO (BCOP Laser Light-Based Opacitometer), ICE (Isolated Chicken Eye)+histopathology, STE (Short Term Exposure), EpiOcular™ EIT (EpiOcular Eye Irritation Test), EpiOcular™ ET-50 (EpiOcular™ Time-to-toxicity), SkinEthic™ HCE EIT (SkinEthic™ Human Corneal Epithelial Eye Irritation Test), and SMI (Slug Mucosal Irritation). Project management decided to not include the ICE data in this project since the execution showed relevant, and not predictable, deviations from Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 438 and Guidance Document 160. At this stage, the outcome of these deviations has not been fully assessed. In addition to these alternative test methods, the computational models Toxtree and Case Ultra were taken into account. This project assessed the relevance of these test methods, their applicability domains and limitations in terms of 'drivers of classification', and their strengths and weaknesses. In this way, methods were identified that fit into a tiered-testing strategy for serious eye damage/eye irritation assessment to distinguish United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS) Category 1 (Cat 1) chemicals from non-Cat 1 chemicals and address the gap namely distinguish between Category 2 (Cat 2) and Cat 1 chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Benzalkonium chloride neutralizes the irritant effect of sodium dodecyl sulfate.

PubMed

McFadden, J P; Holloway, D B; Whittle, E G; Basketter, D A

2000-11-01

When benzalkonium chloride (BKC), a cationic surfactant, is added to sodium dodecyl sulfate (SDS), an anionic surfactant, and used in patch testing, on the basis of their known physicochemical interaction, it is possible to predict that there will be a tendency towards a reduction in the expected irritant response when compared to SDS alone. The aim of this study was to investigate whether BKC could reduce the irritant response to SDS when applied after the SDS exposure. 54 non-atopic adult volunteers were recruited for the study. 20% SDS was applied for 2 h under occlusion. 1% BKC was then applied to the same site. Various controls, including SDS application followed by water for 2 h, were included. The irritant reaction was assessed at 24 h and 48 h. 40 of the 54 subjects had some reaction when SDS was applied for 2 h followed by either benzalkonium chloride or water control under occlusion. In comparison to water control, where BKC was applied after SDS, 20 of the 40 responders had a weaker reaction but only 4 had a stronger response. This study shows that BKC applied to skin exposed to SDS attenuates the resulting irritant reaction.

Enhancing blood donor skin disinfection using natural oils.

PubMed

Alabdullatif, Meshari; Boujezza, Imen; Mekni, Mohamed; Taha, Mariam; Kumaran, Dilini; Yi, Qi-Long; Landoulsi, Ahmed; Ramirez-Arcos, Sandra

2017-12-01

Effective donor skin disinfection is essential in preventing bacterial contamination of blood components with skin flora bacteria like Staphylococcus epidermidis. Cell aggregates of S. epidermidis (biofilms) are found on the skin and are resistant to the commonly used donor skin disinfectants chlorhexidine-gluconate and isopropyl alcohol. It has been demonstrated that essential oils synergistically enhance the antibacterial activity of chlorhexidine-gluconate. The objective of this study was to test plant-extracted essential oils in combination with chlorhexidine-gluconate or chlorhexidine-gluconate plus isopropyl alcohol for their ability to eliminate S. epidermidis biofilms. The composition of oils extracted from Artemisia herba-alba, Lavandula multifida, Origanum marjoram, Rosmarinus officinalis, and Thymus capitatus was analyzed using gas chromatography-mass spectrometry. A rabbit model was used to assess skin irritation caused by the oils. In addition, the anti-biofilm activity of the oils used alone or in combination with chlorhexidine-gluconate or chlorhexidine-gluconate plus isopropyl alcohol was tested against S. epidermidis biofilms. Essential oil concentrations 10%, 20%, and 30% were chosen for anti-biofilm assays, because skin irritation was observed at concentrations greater than 30%. All oils except for O. marjoram had anti-biofilm activity at these three concentrations. L. multifida synergistically enhanced the anti-biofilm activity of chlorhexidine-gluconate and resulted in the highest anti-biofilm activity observed when combined with chlorhexidine-gluconate plus isopropyl alcohol. Gas chromatography-mass spectrometry revealed that the main component contributing to the activity of L. multifida oil was a natural terpene alcohol called linalool. The anti-biofilm activity of chlorhexidine-gluconate plus isopropyl alcohol can be greatly enhanced by L. multifida oil or linalool. Therefore, these components could potentially be used to improve blood

Irritant and cytotoxic coumarins from Angelica glauca Edgew roots.

PubMed

Saeed, M Asif; Sabir, A W

2008-01-01

Irritant and cytotoxic potentiality of six coumarins, isolated for the first time from the roots of Angelica glauca identified as 5,6,7-trimethoxycoumarin, 6-methoxy-7,8-methylenedioxycoumarin, bergapten, decursinol angelate, decursin, and nodakenetin, were investigated. The irritant potential was explored by open mouse ear assay, evaluating their ID(50) after acute and by IU (Irritant units) after chronic effects, while the cytotoxic capability was explored by their LC(50), using brine shrimp (Artemia salina) larvae (nauplii). All the coumarins exhibited well-defined irritancy on mouse's ears, compared with the positive controlled euphorbium reaction and cytotoxic response against brine shrimp larvae, compared with the positive control colchicine. Decursinol angelate and decursin were the most potent and persistent irritant compounds with least ID(50), whose reactions lasted for 48 h. 6-Methoxy-7,8-methylenedioxycoumarin and bergaten revealed an intermediate irritant reactions, while 5,6,7-trimethoxycoumarin and nodakenetin displayed the least irritant and least persistent reactions on mouse ears. Both decursin and decursinol angelate also appeared to be the stronger cytotoxic agents than other coumarins. 5,6,7-trimethoxycoumarin displayed an intermediate cytotoxic behaviour, while other three coumarins, i.e., 6-methoxy-7,8-methylenedioxycoumarin, bergapten, and nodakenetin, exhibited the least cytotoxic capacity against brine shrimp larvae.

Cyclic peptides as potential therapeutic agents for skin disorders.

PubMed

Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

Irritability in Pediatric Patients: Normal or Not?

PubMed Central

Hameed, Usman; Dellasega, Cheryl A.

2016-01-01

The goal of this article is to describe the concept of irritability in children and youth, which has been revisited in the DSM-5. Traditionally, this behavior has been more commonly associated with mood disorders, which may account for the rising incidence of bipolar disorder diagnosis and overuse of mood-stabilizing medications in pediatric patients. While not predictive of mania, persistent nonepisodic irritability, if undetected, may escalate to violent behavior with potentially serious outcomes. It is therefore important to educate clinicians about how to accurately assess irritability in pediatric patients. PMID:27486529

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.

Acrolein Causes TRPA1-Mediated Sensory Irritation and Indirect Potentiation of TRPV1-Mediated Pulmonary Chemoreflex Response

EPA Science Inventory

We previously demonstrated that acute exposure to acrolein causes immediate sensory irritation, with rapid decrease in heart rate (HR) and increase in inspiratory time (Ti), and potentiation of pulmonary chemoreflex response 24hrs later; of these effects only the latter is mediat...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Skin potential measurement device. 882.1560 Section 882.1560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential...

The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.

PubMed

Dhondt, Marijke M M; Adriaens, Els; Roey, Jens Van; Remon, Jean Paul

2005-08-01

The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.

Irritant contact dermatitis due to ammonium bifluoride in two infant twins.

PubMed

Toledo, Fernando; Silvestre, Juan Francisco; Cuesta, Laura; Bañuls, José

2013-01-01

Ammonium bifluoride is one of the most corrosive acids that may produce severe chemical burns when in contact with skin. This hazardous chemical is widely used in household products. We report two pediatric cases of irritant contact dermatitis after exposure to a rust remover, which contained ammonium bifluoride. © 2011 Wiley Periodicals, Inc.

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

PubMed

Cheong, Wai Kwong

2009-01-01

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

Physical characteristic and irritation index of Syzigium aromaticum essential oil in O/W and W/O creams

NASA Astrophysics Data System (ADS)

Safriani, R.; Sugihartini, N.; Yuliani, S.

2017-11-01

Essential oil of Syzigium aromaticum has been formulated in O/W and W/O creams as anti-inflammatory dosage form. The purpose of this study was to evaluate the physical characteristic and irritation index of S. aromaticum essential oil in O/W and W/O creams. The creams were made by fusion method. The creams then were evaluated the physical characteristic including pH, viscosity, spreadability and adhesivity. The irritation index was obtained by irritation skin test in male rabbit. The results showed that the W/O and O/W creams have the value of pH: 6.3 and 6.27; spreadability: 3,18 and 4.17 cm2; adhesivity: 5.59 and 0.07 minutes; viscosity: 4.43 and 2.88 Pa.S, respectively. The irritation test showed that the control enhancer caused mild irritation in both of W/O and O/W creams. These findings indicated that type of cream might influence the physical characteristic and irritation index of S. aromaticum essential oil cream.

Efficacy, Safety, and Subject Satisfaction of a Specified Skin Care Regimen to Cleanse, Medicate, Moisturize, and Protect the Skin of Patients Under Treatment for Acne Vulgaris

PubMed Central

Del Rosso, James Q.; Gold, Michael; Rueda, Maria José; Brandt, Staci; Winkelman, Warren J.

2015-01-01

Optimal management of acne vulgaris requires incorporation of several components including patient education, selection of a rational therapeutic regimen, dedicated adherence with the program by the patient, and integration of proper skin care. Unfortunately, the latter component is often overlooked or not emphasized strongly enough to the patient. Proper skin care may reduce potential irritation that can be associated with topical acne medications and prevents the patient from unknowingly using skin care products that can actually sabotage their treatment. This article reviews the effectiveness, skin tolerability, safety, and patient satisfaction of an open label study in which a specified skin care regimen is used in combination with topical therapy. The study was designed to mirror “real world” management of facial acne vulgaris clinical practice. The skin care regimen used in this study included a brand foam wash and a brand moisturizer with SPF 30 photoprotection, both of which contain ingredients that are included to provide benefits for acne-prone and acne-affected skin. PMID:25610521

Male skin and ingredients relevant to male skin care.

PubMed

Draelos, Z D

2012-03-01

Male skin care needs are heavily influenced by the need to remove facial hair on a regular basis. Facial skin issues associated with poor hair removal approaches are common and include razor burn and irritation. This paper evaluates current research on shaving technology and how careful ingredient selection can contribute to male skin health. The importance of maintaining hair softness during the shave and restoring facial hydration post-shave is discussed. Data are presented on how post-shave moisturizers containing glycerine and emollients can create an environment for improved barrier function which can be further improved by incorporating specific ingredients such as niacinamide. © 2012 The Author. BJD © 2012 British Association of Dermatologists.

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

PubMed

Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

2017-12-01

Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.

Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

PubMed

Song, Aihua; Su, Zhen; Li, Sanming; Han, Fei

2015-01-01

In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

Skin optical clearing potential of disaccharides

NASA Astrophysics Data System (ADS)

Feng, Wei; Shi, Rui; Ma, Ning; Tuchina, Daria K.; Tuchin, Valery V.; Zhu, Dan

2016-08-01

Skin optical clearing can significantly enhance the ability of biomedical optical imaging. Some alcohols and sugars have been selected to be optical clearing agents (OCAs). In this work, we paid attention to the optical clearing potential of disaccharides. Sucrose and maltose were chosen as typical disaccharides to compare with fructose, an excellent monosaccharide-OCA, by using molecular dynamics simulation and an ex vivo experiment. The experimental results indicated that the optical clearing efficacy of skin increases linearly with the concentration for each OCA. Both the theoretical predication and experimental results revealed that the two disaccharides exerted a better optical clearing potential than fructose at the same concentration, and sucrose is optimal. Since maltose has an extremely low saturation concentration, the other two OCAs with saturation concentrations were treated topically on rat skin in vivo, and optical coherence tomography imaging was applied to monitor the optical clearing process. The results demonstrated that sucrose could cause a more significant increase in imaging depth and signal intensity than fructose.

Predictive performance and inter-laboratory reproducibility in assessing eye irritation potential of water- and oil-soluble mixtures using the Short Time Exposure test method.

PubMed

Abo, Takayuki; Hilberer, Allison; Behle-Wagner, Christine; Watanabe, Mika; Cameron, David; Kirst, Annette; Nukada, Yuko; Yuki, Takuo; Araki, Daisuke; Sakaguchi, Hitoshi; Itagaki, Hiroshi

2018-04-01

The Short Time Exposure (STE) test method is an alternative method for assessing eye irritation potential using Statens Seruminstitut Rabbit Cornea cells and has been adopted as test guideline 491 by the Organisation for Economic Co-operation and Development. Its good predictive performance in identifying the Globally Harmonized System (GHS) No Category (NC) or Irritant Category has been demonstrated in evaluations of water-soluble substances, oil-soluble substances, and water-soluble mixtures. However, the predictive performance for oil-soluble mixtures was not evaluated. Twenty-four oil-soluble mixtures were evaluated using the STE test method. The GHS NC or Irritant Category of 22 oil-soluble mixtures were consistent with that of a Reconstructed human Cornea-like Epithelium (RhCE) test method. Inter-laboratory reproducibility was then confirmed using 20 water- and oil-soluble mixtures blind-coded. The concordance in GHS NC or Irritant Category among four laboratories was 90%-100%. In conclusion, the concordance in comparison with the results of RhCE test method using 24 oil-soluble mixtures and inter-laboratory reproducibility using 20 water- and oil-soluble mixtures blind-coded were good, indicating that the STE test method is a suitable alternative for predicting the eye irritation potential of both substances and mixtures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Skin diseases during floods in Thailand.

PubMed

Vachiramon, Vasanop; Busaracome, Ploysyne; Chongtrakool, Piriyaporn; Puavilai, Siripen

2008-04-01

Floods are natural disasters that occur occasionally in Thailand. The most common form skin diseases due to floods are infectious dermatoses especially superficial fungal infection. However the microbiologic evidences have not been evaluated. To evaluate the most common skin diseases during floods and identify the organism that causes skin maceration at web space(s) of toes (Hong Kong foot). Patients who complained of skin problems were evaluated at the temporary outpatient clinic during October 2006. Skin specimens from all patients who had itches and skin maceration at web space(s) of toes were cultured. Ninety-six patients were evaluated (38 males and 58 females). Eczema was the most prevalent dermatosis, which accounted for 34.5% of the total skin problems and the great majority of these cases were irritant contact dermatitis. Sixteen cases presented with itch and skin maceration at web space(s) of toes. All of them were colonized with various microorganisms. Gram-negative bacilli were the most prevalent ones and were found in 14 out of 16 specimens. Fungal culture was positive in only two specimens. Eczema is the most common dermatosis during floods. Skin maceration at web space(s) of toes, which were thought to be fungal infection, are chronic irritant dermatitis with secondary bacterial colonization. Only a few cases were fungal infection. Microbiologic investigation should be done in these patients. Unfortunately, it is not practical in such a situation. Topical medications that have the combination of antiinflammatory, antibacterial and antifungal properties are the most suitable medications.

Evaluation of a topical treatment for the relief of sensitive skin

PubMed Central

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

2015-01-01

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

Beneficial effects of softened fabrics on atopic skin.

PubMed

Hermanns, J F; Goffin, V; Arrese, J E; Rodriguez, C; Piérard, G E

2001-01-01

There is general concern about the possible cutaneous adverse effects of wearing garments treated with household laundry products, particularly on atopic skin. Our objective was to compare softened and non- softened fabrics in a forearm wet and dry test, under conditions simulating real-life conditions. Twenty atopic volunteers entered a single-blind 12-day (3 sessions per day) forearm wetting and drying test. Cotton fabrics were machine washed and liquid fabric conditioner was added or not to the final rinse. To simulate conditions of skin damage, a dilute solution of sodium lauryl sulphate was applied under occlusion to the forearm of each volunteer before the start of the study. Skin effects were evaluated by visual grading (redness, dryness and smoothness), squamometry and in vivo instrumental measurements (capacitance, transepidermal water loss and colorimetry). Rubbing of atopic skin with fabrics generally resulted in discrete to moderate alterations of the structure of the stratum corneum. Both for control and pre-irritated skin, all measured parameters indicated that softened fabric was less aggressive to the skin than unsoftened fabric. In the case of pre-irritated skin, the recovery of the skin was significantly faster when rubbed with softened than with unsoftened fabrics. In conclusion, softened fabrics help mitigate the skin condition in atopic patients. Copyright 2001 S. Karger AG, Basel.

Optimizing management of actinic keratosis and photodamaged skin: utilizing a stepwise approach.

PubMed

Lee, Andrew D; Jorizzo, Joseph L

2009-09-01

The incidence of photodamaged skin and skin lesions of all degrees of severity, from actinic keratosis (AK) to skin cancers, has dramatically increased. Actinic keratoses are pathologic, reflecting damage of essential skin cell functions and potentially progressing to invasive squamous cell carcinoma (SCC). The rate of progression is uncertain but may be as high as 10%. Because it is impossible to predict which AKs will progress to SCC, all lesions should be treated. Options include topical therapies, cryotherapy, curettage, and photodynamic therapy. Unfortunately, many individuals do not seek treatment or avoid it because of irritation, discomfort, and concern for scarring. Combining field-directed therapy and cryotherapy has been more effective than cryotherapy alone. Incorporating patient education with treatment may optimize outcomes. We propose a comprehensive 5-step approach for managing AK lesions and photodamaged skin that includes periodic clinical skin examinations; treating AK lesions with a combination of field- and lesion-directed therapy; and patient education regarding sun-protective measures and regular skin self-examinations.

A new, female-specific irritability rating scale

PubMed Central

Born, Leslie; Koren, Gideon; Lin, Elizabeth; Steiner, Meir

2008-01-01

Objective Irritability is a prominent symptom in the spectrum of female-specific mood disorders, and in some women, irritability is serious enough to disrupt their lives and warrant treatment. The objective of this research was to develop a new, female-specific state measure of irritability. Methods We constructed self-rating and observer rating scales using items derived from spontaneous descriptions of irritability by women with mood disturbances related to the menstrual cycle, childbearing or menopause. Following a pretest, the scales were shortened to the core items of irritability (annoyance, anger, tension, hostility, sensitivity to noise and touch) and tested on a new cohort of patients. Results The 14-item Self-Rating Scale and the 5-item Observer Rating Scale showed evidence for internal consistency (Self-Rating: n = 36 patients, Cronbach's α = 0.9257, mean interitem correlation = 0.4690; Observer Rating: Cronbach's α = 0.7418, mean interitem correlation = 0.3616), Self-Rating test–retest reliability (n = 29 patients, rs = 0.704, p = 0.01) and interrater reliability (n = 20 patients; τb = 1.000, p = 0.001). Conclusion This new, female-specific scale for rating irritability has the potential to further the evaluation of this prominent symptom cluster and increase specificity in clinical assessments of emotional disturbances related to reproductive cyclicity in women. PMID:18592028

Clinical potential of a silk sericin-releasing bioactive wound dressing for the treatment of split-thickness skin graft donor sites.

PubMed

Siritientong, Tippawan; Angspatt, Apichai; Ratanavaraporn, Juthamas; Aramwit, Pornanong

2014-01-01

An ethyl alcohol-precipitated silk sericin/PVA scaffold that controlled the release of silk sericin was previously developed and applied for the treatment of full-thickness wounds in rats and demonstrated efficient healing. In this study, we aimed to further evaluate the clinical potential of this scaffold, hereafter called "silk sericin-releasing wound dressing", for the treatment of split-thickness skin graft donor sites by comparison with the clinically available wound dressing known as "Bactigras®". In vitro characterization and in vivo evaluation for safety of the wound dressings were performed. A clinical trial of the wound dressings was conducted according to standard protocols. The sericin released from the wound dressing was not toxic to HaCat human keratinocytes. A peel test indicated that the silk sericin-releasing wound dressing was less adhesive than Bactigras®, potentially reducing trauma and the risk of repeated injury upon removal. There was no evidence of skin irritation upon treatment with either wound dressing. When tested in patients with split-thickness skin graft donor sites, the wounds treated with the silk sericin-releasing wound dressing exhibited complete healing at 12 ± 5.0 days, whereas those treated with Bactigras® were completely healed at 14 ± 5.2 days (p = 1.99 × 10(-4)). In addition, treatment with the silk sericin-releasing wound dressing significantly reduced pain compared with Bactigras® particularly during the first 4 postoperative days (p = 2.70 × 10(-5) on day 1). We introduce this novel silk sericin-releasing wound dressing as an alternative treatment for split-thickness skin graft donor sites.

Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety

PubMed Central

Mukherjee, Siddharth; Date, Abhijit; Patravale, Vandana; Korting, Hans Christian; Roeder, Alexander; Weindl, Günther

2006-01-01

Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy of retinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids. PMID:18046911

Effect of different alcohols on stratum corneum kallikrein 5 and phospholipase A2 together with epidermal keratinocytes and skin irritation.

PubMed

Cartner, T; Brand, N; Tian, K; Saud, A; Carr, T; Stapleton, P; Lane, M E; Rawlings, A V

2017-04-01

The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function. Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study. Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P < 0.001), and in the case of PLA2, the effect of isopropanol was greater than ethanol (P < 0.001). Equally, ethanol had the mildest effects on keratinocyte metabolic activity and cytokine secretion (P < 0.001) and n-propanol always produced the most severe changes in normal and differentiated keratinocytes. These in vitro findings supported the clinical results where the major effects were on the induction of skin irritation (increased dropout rates) and ranked the intolerance of the different alcohols as follows: n-propanol > isopropanol > ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P < 0.05). Equally, n-propanol and isopropanol produced significantly more skin redness at the low application frequencies. Clearly, isopropanol and n-propanol caused significant SC and keratinocyte perturbation in vitro together with damage to skin condition and function in vivo whereas ethanol

Effectiveness of interventions for preventing occupational irritant hand dermatitis: a quantitative systematic review protocol.

PubMed

Papadatou, Zoi; Cooper, Kay; Klein, Susan; MacDuff, Colin; Steiner, Markus

2016-10-01

The objective of this quantitative systematic review is to identify, appraise and synthesize the best available evidence on the effectiveness of moisturizers, barrier creams, protective gloves, skin protection education and complex interventions (a combination of two or more of the interventions listed) in preventing occupational irritant hand dermatitis (OIHD) in wet workers. These interventions will be compared to an alternative intervention or to usual care (workers regular skin care regime). The specific review question is: "What is the effectiveness of moisturizers, barrier creams, protective gloves, skin protection education and complex interventions in preventing OIHD in wet workers?"

Topical use of dexpanthenol in skin disorders.

PubMed

Ebner, Fritz; Heller, Andreas; Rippke, Frank; Tausch, Irene

2002-01-01

Pantothenic acid is essential to normal epithelial function. It is a component of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions that are important in the metabolism of carbohydrates, fatty acids, proteins, gluconeogenesis, sterols, steroid hormones, and porphyrins. The topical use of dexpanthenol, the stable alcoholic analog of pantothenic acid, is based on good skin penetration and high local concentrations of dexpanthenol when administered in an adequate vehicle, such as water-in-oil emulsions. Topical dexpanthenol acts like a moisturizer, improving stratum corneum hydration, reducing transepidermal water loss and maintaining skin softness and elasticity. Activation of fibroblast proliferation, which is of relevance in wound healing, has been observed both in vitro and in vivo with dexpanthenol. Accelerated re-epithelization in wound healing, monitored by means of the transepidermal water loss as an indicator of the intact epidermal barrier function, has also been seen. Dexpanthenol has been shown to have an anti-inflammatory effect on experimental ultraviolet-induced erythema. Beneficial effects of dexpanthenol have been observed in patients who have undergone skin transplantation or scar treatment, or therapy for burn injuries and different dermatoses. The stimulation of epithelization, granulation and mitigation of itching were the most prominent effects of formulations containing dexpanthenol. In double-blind placebo-controlled clinical trials, dexpanthenol was evaluated for its efficacy in improving wound healing. Epidermal wounds treated with dexpanthenol emulsion showed a reduction in erythema, and more elastic and solid tissue regeneration. Monitoring of transepidermal water loss showed a significant acceleration of epidermal regeneration as a result of dexpanthenol therapy, as compared with the vehicle. In an irritation model, pretreatment with dexpanthenol cream resulted in significantly less damage to the stratum

Potential of herbs in skin protection from ultraviolet radiation

PubMed Central

Korać, Radava R.; Khambholja, Kapil M.

2011-01-01

Herbs have been used in medicines and cosmetics from centuries. Their potential to treat different skin diseases, to adorn and improve the skin appearance is well-known. As ultraviolet (UV) radiation can cause sunburns, wrinkles, lower immunity against infections, premature aging, and cancer, there is permanent need for protection from UV radiation and prevention from their side effects. Herbs and herbal preparations have a high potential due to their antioxidant activity, primarily. Antioxidants such as vitamins (vitamin C, vitamin E), flavonoids, and phenolic acids play the main role in fighting against free radical species that are the main cause of numerous negative skin changes. Although isolated plant compounds have a high potential in protection of the skin, whole herbs extracts showed better potential due to their complex composition. Many studies showed that green and black tea (polyphenols) ameliorate adverse skin reactions following UV exposure. The gel from aloe is believed to stimulate skin and assist in new cell growth. Spectrophotometer testing indicates that as a concentrated extract of Krameria triandra it absorbs 25 to 30% of the amount of UV radiation typically absorbed by octyl methoxycinnamate. Sesame oil resists 30% of UV rays, while coconut, peanut, olive, and cottonseed oils block out about 20%. A “sclerojuglonic” compound which is forming from naphthoquinone and keratin is the reaction product that provides UV protection. Traditional use of plant in medication or beautification is the basis for researches and making new trends in cosmetics. This review covers all essential aspects of potential of herbs as radioprotective agents and its future prospects. PMID:22279374

Natural Oils for Skin-Barrier Repair: Ancient Compounds Now Backed by Modern Science.

PubMed

Vaughn, Alexandra R; Clark, Ashley K; Sivamani, Raja K; Shi, Vivian Y

2018-02-01

Natural plant oils are commonly used as topical therapy worldwide. They are usually easily accessible and are relatively inexpensive options for skin care. Many natural oils possess specific compounds with antimicrobial, antioxidant, anti-inflammatory, and anti-itch properties, making them attractive alternative and complementary treatments for xerotic and inflammatory dermatoses associated with skin-barrier disruption. Unique characteristics of various oils are important when considering their use for topical skin care. Differing ratios of essential fatty acids are major determinants of the barrier repair benefits of natural oils. Oils with a higher linoleic acid to oleic acid ratio have better barrier repair potential, whereas oils with higher amounts of irritating oleic acid may be detrimental to skin-barrier function. Various extraction methods for oils exist, including cold pressing to make unrefined oils, heat and chemical distillation to make essential oils, and the addition of various chemicals to simulate a specific scent to make fragranced oils. The method of oil processing and refinement is an important component of selecting oil for skin care, and cold pressing is the preferred method of oil extraction as the heat- and chemical-free process preserves beneficial lipids and limits irritating byproducts. This review summarizes evidence on utility of natural plant-based oils in dermatology, particularly in repairing the natural skin-barrier function, with the focus on natural oils, including Olea europaea (olive oil), Helianthus annus (sunflower seed oil), Cocos nucifera (coconut oil), Simmondsia chinesis (jojoba oil), Avena sativa (oat oil), and Argania spinosa (argan oil).

Skin intervention of fullerene-integrated nanoemulsion in structural and collagen regeneration against skin aging.

PubMed

Ngan, Cheng Loong; Basri, Mahiran; Tripathy, Minaketan; Abedi Karjiban, Roghayeh; Abdul-Malek, Emilia

2015-04-05

Despite the fact that intrinsic oxidative stress is inevitable, the extrinsic factor such as ultraviolet radiation enhances reactive oxygen species (ROS) generation resulting in premature skin aging. Nanoemulsion was loaded with fullerene, a strong free radical scavenger, and its efficacy to provide protection and regenerative effect against ROS-induced collagen breakdown in human skin was studied. Stable fullerene nanoemulsions were formulated using high shear homogenization and ultrasonic dispersion technique. An open trial was conducted using fullerene nanoemulsion on skin twice a day for 28 days. The mean collagen score significantly increased (P<0.05) from 36.53±4.39 to 48.69±5.46 with 33.29% increment at the end of the treatment. Biophysical characteristics of skin revealed that skin hydration was increased significantly (P<0.05) from 40.91±7.01 to 58.55±6.08 corneometric units (43.12% increment) and the water was able to contain within the stratum corneum without any increased in transepidermal water loss. In the in vitro safety evaluation, fullerene nanoemulsion showed no acute toxicity on 3T3 fibroblast cell line for 48h and no indication of potential dermal irritation. Hence, the fullerene nanoemulsion may assist in protecting collagen from breakdown with cosmeceutical benefit. Copyright © 2015 Elsevier B.V. All rights reserved.

Seeking Clearer Recommendations for Hand Hygiene in Communities Facing Ebola: A Randomized Trial Investigating the Impact of Six Handwashing Methods on Skin Irritation and Dermatitis.

PubMed

Wolfe, Marlene K; Wells, Emma; Mitro, Brittany; Desmarais, Anne Marie; Scheinman, Pamela; Lantagne, Daniele

2016-01-01

To prevent disease transmission, 0.05% chlorine solution is commonly recommended for handwashing in Ebola Treatment Units. In the 2014 West Africa outbreak this recommendation was widely extended to community settings, although many organizations recommend soap and hand sanitizer over chlorine. To evaluate skin irritation caused by frequent handwashing that may increase transmission risk in Ebola-affected communities, we conducted a randomized trial with 91 subjects who washed their hands 10 times a day for 28 days. Subjects used soap and water, sanitizer, or one of four chlorine solutions used by Ebola responders (calcium hypochlorite (HTH), sodium dichloroisocyanurate (NaDCC), and generated or pH-stabilized sodium hypochlorite (NaOCl)). Outcomes were self-reported hand feel, irritation as measured by the Hand Eczema Score Index (HECSI) (range 0-360), signs of transmission risk (e.g., cracking), and dermatitis diagnosis. All groups experienced statistically significant increases in HECSI score. Subjects using sanitizer had the smallest increases, followed by higher pH chlorine solutions (HTH and stabilized NaOCl), and soap and water. The greatest increases were among neutral pH chlorine solutions (NaDCC and generated NaOCl). Signs of irritation related to higher transmission risk were observed most frequently in subjects using soap and least frequently by those using sanitizer or HTH. Despite these irritation increases, all methods represented minor changes in HECSI score. Average HECSI score was only 9.10 at endline (range 1-33) and 4% (4/91) of subjects were diagnosed with dermatitis, one each in four groups. Each handwashing method has benefits and drawbacks: soap is widely available and inexpensive, but requires water and does not inactivate the virus; sanitizer is easy-to use and effective but expensive and unacceptable to many communities, and chlorine is easy-to-use but difficult to produce properly and distribute. Overall, we recommend Ebola responders and

Studies on the relationship between epidermal cell turnover kinetics and permeability of hairless mouse skin

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

Han, S.R.

The primary aim of this study was to develop non-invasive, physical means to quantitatively assess the epidermal turnover kinetics and barrier properties of the skin and relate these to the cutaneous irritation which results from ultraviolet light irradiation and mold thermal burns. After systematically injecting radiolabeled glycine, the appearance of radioactivity at the skin's surface indicated the transit time of radiolabeled cells through the skin. By plotting the data as the cumulative specific activity against time and then fitting them with a third order polynomial equation, it is possible to estimate the turnover time of the stratum corneum. The skinmore » turnover was coordinated with non-invasive transepidermal water loss (TEWL) studies determined with an evaporimeter. In vitro diffusion studies of the permeability of hydrocortisone through UVB irradiated and thermally burned skin were also performed. The studies indicated that irritated skin offers a relatively low diffusional resistance to hydrocortisone. Depending on the severity of the trauma, the increases in hydrocortisone's permeability coefficient through irritated skin ranged from a low of about 2 times normal to a high of about 210 times normal. Trauma-induced changes in hydrocortisone permeability parallel changes in TEWL, proving that the barrier deficient state resulting from rapid epidermal turnover is a general phenomenon.« less

Evaluation of Ocular Irritation and Bioavailability of Voriconazole Loaded Microemulsion.

PubMed

Kumar, Rakesh; Sinha, Vivek Ranjan

2017-01-01

Voriconazole (VCZ), a second-generation antifungal with excellent attributes like, broad-spectrum activity, targeted delivery, and tolerability. VCZ loaded microemulsion could be an effective strategy for efficient ocular delivery of the drug. To perform corneal irritation studies and in vivo delivery of VCZ microemulsion to establish its potential as an efficient ocular delivery system. Ocular irritancy was performed by HETCAM (Hen's Egg Test Chorio Allantoic Membrane) assay, corneal histopathology and Draize test. Ex vivo and in vivo studies were performed to determine permeation efficiency of VCZ microemulsion. The irritation studies suggested the non-irritant nature of the microemulsion. The ex vivo studies performed on excised cornea displayed significant enhancement in drug permeation/penetration from microemulsion in contrast to the drug suspension. Further, the in vivo study confirmed the higher availability of VCZ (from microemulsion) in aqueous humor with minimal nasolacrimal drainage (lower plasma drug content) when compared with the drug suspension. The non-irritant nature and high corneal permeation of VCZ encourages the role of microemulsion as a potential ocular delivery system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The developmental psychopathology of irritability

PubMed Central

LEIBENLUFT, ELLEN; STODDARD, JOEL

2015-01-01

Chronic, severe irritability is common in childhood and is very impairing. Furthermore, childhood irritability predicts suicidality, social impairment, and depressive and anxiety disorders in adulthood. Focusing on both normative and pathologic development, we review the construct of irritability from its origins in aggression and disruptive behavior research to its contemporary relevance for affective psychopathology. We then describe two broad neurocognitive systems that show promise in differentiating irritable from nonirritable youths: aberrant processing of emotional stimuli and impaired context-sensitive regulation. We suggest behavioral, neurocognitive, and physiologic measures that may aid in studying severe irritability and assessing its therapeutics. Finally, we argue for therapeutic trials targeting severe irritability that address emotional aspects of irritability in addition to the associated disruptive behavior. PMID:24342851

Correlates of Irritability in College Students With Depressive Symptoms

PubMed Central

Pedrelli, Paola; Nyer, Maren; Holt, Daphne; Bakow, Brianna R.; Fava, Maurizio; Baer, Lee; Cassiello, Clair; Mulligan, Maura; Cusin, Cristina; Farabaugh, Amy

2015-01-01

Depression is a prevalent psychiatric disorder associated with significant personal and societal burden. There is accumulating evidence for the presence of a subtype of depression characterized by the presence of irritability that is associated with increased morbidity, risk for suicidal ideation, and functional impairments in adults. Little is known about the features of depressive symptoms with and without irritability among young adults in college. The primary aim of this study was to characterize the presentation of college students with depressive symptoms and irritability. Two-hundred eighty-seven undergraduate college students with depressive symptoms with and without irritability were compared across several psychiatric and functional outcome variables. Independent samples t-tests or logistic regressions were conducted for each outcome variable using the irritability item of the Beck Depression Inventory as a dichotomous grouping variable. Analyses were conducted separately for the men and the women. Both male and female students with depressive symptoms and severe irritability reported a greater severity of depressive symptoms compared with their peers with no or mild irritability. In the women, the presence of irritability was associated with greater symptoms of anxiety, whereas in the men, it was associated with increased likelihood of engaging in risky behaviors, including compulsive use of alcohol, illicit drugs, and prescription drugs. The male and female college students with depressive symptoms with and without irritability did not differ on severity of suicidal ideation, hopelessness, or cognitive functioning. The findings from this study suggest that depressive symptoms and irritability may characterize a subtype of college students who have a greater symptom burden and with the potential need for more aggressive and prompt treatment. PMID:24177482

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

PubMed

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

2018-02-28

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

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.

Distribution of phospholipid based formulations in the skin investigated by combined ATR-FTIR and tape stripping experiments.

PubMed

Wolf, Martin; Halper, Maria; Pribyl, Raffaela; Baurecht, Dieter; Valenta, Claudia

2017-03-15

The spatial distribution of exogenous substances in the stratum corneum (SC) could have an influence on their skin irritation potential. In this study it was possible to monitor the distribution of phospholipids with their phosphatidylcholine scaffold on porcine ear skin by combining tape stripping and in vitro ATR-FTIR spectroscopy. Significant vibrational modes in the spectra could be successfully assigned to the functional groups of the molecules. Thus it was possible to track the phospholipids without the need of their deuterated form by calculating difference spectra from the treated - untreated skin samples. The correlation between four characteristic bands (R 2 ≥0.9909) revealed the excellent suitability of this semi-quantitative method for deep profiling analysis. The penetration capabilities of aqueous suspensions of the different phospholipid compositions as well as two monoacyl-phosphatidylcholine based liposome formulations were investigated using this method. Nevertheless, differences in the distribution of the investigated phospholipid species, having different amounts of monoacyl-phosphatidylcholine, could not be found. It could be clearly shown that the deepest skin penetration was seen in the irritating anionic SDS (sodium dodecyl sulfate) out of the aqueous solution. The aqueous suspensions based on different phospholipid surfactants showed the same range of penetration depth (10-15% of SC), whereas the smallest skin penetration depth was observed after the application of liposomal formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances.

PubMed

Savić, Vedrana; Todosijević, Marija; Ilić, Tanja; Lukić, Milica; Mitsou, Evgenia; Papadimitriou, Vassiliki; Avramiotis, Spyridon; Marković, Bojan; Cekić, Nebojša; Savić, Snežana

2017-08-30

In order to improve skin penetration of tacrolimus we aimed to develop potentially non-irritant, lecithin-based microemulsions containing ethanol, isopropanol and/or propylene glycol as cosurfactants, varying caprylic/capric triglycerides and propylene glycol monocaprylate as oil phase. The influence of excipients on the size of microemulsion region in pseudo-ternary phase diagrams and their ability to form different types of microemulsions was evaluated. The comprehensive physicochemical characterization of microemulsions and the evaluation of their structure was performed, while the localization of tacrolimus in microemulsions was further investigated using electron paramagnetic resonance spectroscopy. Moreover, stability studies proved no change in tacrolimus content during one year of storage at room temperature. In addition, in vivo skin performance indicated no skin irritation potential of blank microemulsions, whereas in vitro release testing using Franz diffusion cells showed superior release rate of tacrolimus from microemulsions (0.98±0.10 and 0.92±0.11μg/cm 2 /h for two bicontinuous and 1.00±0.24μg/cm 2 /h for oil-in-water microemulsion) compared to referent Protopic ointment (0.15±0.08μg/cm 2 /h). Furthermore, ex vivo penetration assessed through porcine ear skin using tape stripping, confirmed superiority of two microemulsions related to the reference, implying developed microemulsions as promising carriers for dermal delivery of tacrolimus. Copyright © 2017 Elsevier B.V. All rights reserved.

The EpiOcular™ Eye Irritation Test is the Method of Choice for the In Vitro Eye Irritation Testing of Agrochemical Formulations: Correlation Analysis of EpiOcular Eye Irritation Test and BCOP Test Data According to the UN GHS, US EPA and Brazil ANVISA Classification Schemes.

PubMed

Kolle, Susanne N; Rey Moreno, Maria Cecilia; Mayer, Winfried; van Cott, Andrew; van Ravenzwaay, Bennard; Landsiedel, Robert

2015-07-01

The Bovine Corneal Opacity and Permeability (BCOP) test is commonly used for the identification of severe ocular irritants (GHS Category 1), but it is not recommended for the identification of ocular irritants (GHS Category 2). The incorporation of human reconstructed tissue model-based tests into a tiered test strategy to identify ocular non-irritants and replace the Draize rabbit eye irritation test has been suggested (OECD TG 405). The value of the EpiOcular™ Eye Irritation Test (EIT) for the prediction of ocular non-irritants (GHS No Category) has been demonstrated, and an OECD Test Guideline (TG) was drafted in 2014. The purpose of this study was to evaluate whether the BCOP test, in conjunction with corneal histopathology (as suggested for the evaluation of the depth of the injury( and/or the EpiOcular-EIT, could be used to predict the eye irritation potential of agrochemical formulations according to the UN GHS, US EPA and Brazil ANVISA classification schemes. We have assessed opacity, permeability and histopathology in the BCOP assay, and relative tissue viability in the EpiOcular-EIT, for 97 agrochemical formulations with available in vivo eye irritation data. By using the OECD TG 437 protocol for liquids, the BCOP test did not result in sufficient correct predictions of severe ocular irritants for any of the three classification schemes. The lack of sensitivity could be improved somewhat by the inclusion of corneal histopathology, but the relative viability in the EpiOcular-EIT clearly outperformed the BCOP test for all three classification schemes. The predictive capacity of the EpiOcular-EIT for ocular non-irritants (UN GHS No Category) for the 97 agrochemical formulations tested (91% sensitivity, 72% specificity and 82% accuracy for UN GHS classification) was comparable to that obtained in the formal validation exercise underlying the OECD draft TG. We therefore conclude that the EpiOcular-EIT is currently the best in vitro method for the prediction

Surfactant irritation: in vitro corneosurfametry and in vivo bioengineering.

PubMed

Gabard, B; Chatelain, E; Bieli, E; Haas, S

2001-02-01

Irritant reactions to surfactants, cleansing products, soaps and detergents are common in clinical and occupational dermatology. Mildness has become a major benefit claimed, and testing for mildness now ranks among the first concerns of the manufacturing industry. A wealth of publications deals with this problem, trying to improve the methodology, reduce the costs of testing and facilitate decision-making. Differences in vivo can be measured clinically and/or instrumentally. This is difficult, as commercially available products are generally safe to use and none are harsh in the absolute sense. Nineteen different products (syndets, shampoos, personal cleansers), all claiming to be mild, were tested in vitro by a newly introduced method, corneosurfametry. For evaluating the aggressiveness of the products, the calculation of an index of irritation (IOI) was proposed. A concentration-effect curve of sodium lauryl sulfate (SLS) as standard and model surfactant was obtained. Some of the products were further tested in vivo with a flex wash test and with a soap chamber test and compared to SLS. Bioengineering methods (transepidermal water loss TEWL, skin color) were used to evaluate the results. The results of the corneosurfametry allowed us to classify the products in three categories, with increasing aggressiveness towards the stratum corneum, according to their IOIs. The in vivo tests were not able to discriminate between the products, but ranks from the results of the bioengineering measurements showed a good correlation between TEWL changes, but not between colour changes, and IOIs from corneosurfametry. Corneosurfametry emerged as a simple, low-cost and fast method for ranking commercial products according to their mildness. However, the skin bioengineering techniques showed that some products could lead to skin reactions, such as erythema, that could not be detected by the in vitro technique.

Skin interaction with absorbent hygiene products.

PubMed

Runeman, Bo

2008-01-01

Skin problems due to the use of absorbent hygiene products, such as diapers, incontinence pads, and feminine sanitary articles, are mostly due to climate or chafing discomfort. If these conditions are allowed to prevail, these may develop into an irritant contact dermatitis and eventually superficial skin infections. Skin humidity and aging skin are among the most significant predisposing and aggravating factors for dermatitis development. Improved product design features are believed to explain the decline in observed diaper dermatitis among infants. Where adult incontinence-related skin problems are concerned, it is very important to apply a holistic perspective to understand the influences due to the individual's incontinence level and skin condition, as well as the hygiene and skin care measures provided. Individuals with frail, sensitive skin or with skin diseases may preferably have to use high-quality products, equipped with superabsorbent polymers and water vapor-permeable back sheets, to minimize the risk of skin complications.

In vivo irritation study of Melastoma malabathricum cream formulation on ICR mice

NASA Astrophysics Data System (ADS)

Yasin, Rabiahtul Adarwiyah Mohd; Jemon, Khairunadwa; Nor, Norefrina Shafinaz Md

2016-11-01

Melastoma malabathricum is a traditional herb that is used to treat wound on skin. It has also been proven to have antiviral activity against Herpes Simplex virus type 1 (HSV-1). In this study, M. malabathricum cream formulation was developed by incorporating M. malabathricum aqueous extract into cream base. The safety and biocompatibility of the formulated cream was investigated by topically applying the cream onto the back of ICR mice skin. Treatment with M. malabathricum was found to accelerate wound contraction with less scar formation. The effect of M. malabathricum has prompted a possibility that M. malabathricum might contribute in enhancing the healing process of cutaneous lesion caused by HSV-1. The formulated cream did not cause any skin irritation or adverse effect to ICR mice when topically applied within seven days of exposure.

Effectiveness of hand washing on the removal of iron oxide nanoparticles from human skin ex vivo.

PubMed

Lewinski, Nastassja A; Berthet, Aurélie; Maurizi, Lionel; Eisenbeis, Antoine; Hopf, Nancy B

2017-08-01

In this study, the effectiveness of washing with soap and water in removing nanoparticles from exposed skin was investigated. Dry, nanoscale hematite (α-Fe 2 O 3 ) or maghemite (γ-Fe 2 O 3 ) powder, with primary particle diameters between 20-30 nm, were applied to two samples each of fresh and frozen ex vivo human skin in two independent experiments. The permeation of nanoparticles through skin, and the removal of nanoparticles after washing with soap and water were investigated. Bare iron oxide nanoparticles remained primarily on the surface of the skin, without penetrating beyond the stratum corneum. Skin exposed to iron oxide nanoparticles for 1 and 20 hr resulted in removal of 85% and 90%, respectively, of the original dose after washing. In the event of dermal exposure to chemicals, removal is essential to avoid potential local irritation or permeation across skin. Although manufactured at an industrial scale and used extensively in laboratory experiments, limited data are available on the removal of engineered nanoparticles after skin contact. Our finding raises questions about the potential consequences of nanoparticles remaining on the skin and whether alternative washing methods should be proposed. Further studies on skin decontamination beyond use of soap and water are needed to improve the understanding of the potential health consequences of dermal exposure to nanoparticles.

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

PubMed

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

2017-10-05

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

Tiered application of the neutral red release and EpiOcular™ assays for evaluating the eye irritation potential of agrochemical formulations.

PubMed

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

2016-11-01

Agrochemical formulations have been underrepresented in validation efforts for implementing alternative eye irritation approaches but represent a significant opportunity to reduce animal testing. This study assesses the utility of the neutral red release assay (NRR) and EpiOcular™ assay (EO) for predicting the eye irritation potential of 64 agrochemical formulations relative to Draize data. In the NRR, formulations with an NRR50 value ≤ 50 mg/mL were categorized as UN GHS Cat 1 and those >250 mg/mL were classified as UN GHS Non Classified (NC). The accuracy, sensitivity, and specificity were 78, 85 and 76% and 73, 85 and 61% for identifying UN GHS 1 and NC formulations, respectively. Specificity was poor for formulations with NRR50 > 50 to ≤250 mg/mL. The EO (ET-40 method) was explored to differentiate formulations that were UN GHS 1/2 and UN GHS NC. The EO resulted in accuracy, sensitivity, and specificity of 65%, 58% and 75% for identifying UN GHS NC formulations. To improve the overall performance, the assays were implemented using a tiered-approach where the NRR was run as a first-tier followed by the EO. The tiered-approach resulted in improved accuracy (75%) and balanced sensitivity (73%) and specificity (77%) for distinguishing between irritating and non-irritating agrochemical formulations. Copyright © 2016 Elsevier Inc. All rights reserved.

Some effects of chemical irritants on the membrane of the giant amoeba.

PubMed Central

Foster, R. W.; Weston, A. H.; Weston, K. M.

1981-01-01

1 The effects of chemical irritants on the membrane potential and input resistance of the giant amoeba, Chaos carolinense, have been investigated. The membrane potential and input resistance were -111.5 mV and 8.6 M pi respectively. 2 In the resting state the cell membrane of Chaos carolinense was found to be impermeable to Na+ but permeable to K+. The distribution of K+ across the cell membrane conformed to a Donnan equilibrium with the resting membrane potential being the K+ equilibrium potential. 3 The chemical irritants dibenzoxazepine and its 2-chloro- and 3-chloro-analogues and o-chlorobenzylidene malononitrile produced a fall in input resistance but no change in membrane potential. It is suggested that these effects are caused by an increase in K+ permeability. 4 The potencies of a series of chemical irritants with respect to dibenzoxazepine were measured on the giant amoeba. These potencies did not reflect those found in mammalian preparations. PMID:6797494

Smartphone-based multispectral imaging: system development and potential for mobile skin diagnosis

PubMed Central

Kim, Sewoong; Cho, Dongrae; Kim, Jihun; Kim, Manjae; Youn, Sangyeon; Jang, Jae Eun; Je, Minkyu; Lee, Dong Hun; Lee, Boreom; Farkas, Daniel L.; Hwang, Jae Youn

2016-01-01

We investigate the potential of mobile smartphone-based multispectral imaging for the quantitative diagnosis and management of skin lesions. Recently, various mobile devices such as a smartphone have emerged as healthcare tools. They have been applied for the early diagnosis of nonmalignant and malignant skin diseases. Particularly, when they are combined with an advanced optical imaging technique such as multispectral imaging and analysis, it would be beneficial for the early diagnosis of such skin diseases and for further quantitative prognosis monitoring after treatment at home. Thus, we demonstrate here the development of a smartphone-based multispectral imaging system with high portability and its potential for mobile skin diagnosis. The results suggest that smartphone-based multispectral imaging and analysis has great potential as a healthcare tool for quantitative mobile skin diagnosis. PMID:28018743

Smartphone-based multispectral imaging: system development and potential for mobile skin diagnosis.

PubMed

Kim, Sewoong; Cho, Dongrae; Kim, Jihun; Kim, Manjae; Youn, Sangyeon; Jang, Jae Eun; Je, Minkyu; Lee, Dong Hun; Lee, Boreom; Farkas, Daniel L; Hwang, Jae Youn

2016-12-01

We investigate the potential of mobile smartphone-based multispectral imaging for the quantitative diagnosis and management of skin lesions. Recently, various mobile devices such as a smartphone have emerged as healthcare tools. They have been applied for the early diagnosis of nonmalignant and malignant skin diseases. Particularly, when they are combined with an advanced optical imaging technique such as multispectral imaging and analysis, it would be beneficial for the early diagnosis of such skin diseases and for further quantitative prognosis monitoring after treatment at home. Thus, we demonstrate here the development of a smartphone-based multispectral imaging system with high portability and its potential for mobile skin diagnosis. The results suggest that smartphone-based multispectral imaging and analysis has great potential as a healthcare tool for quantitative mobile skin diagnosis.

Occupational skin diseases in Czech healthcare workers from 1997 to 2009.

PubMed

Machovcová, A; Fenclová, Z; Pelclová, D

2013-04-01

The healthcare sector ranked in second place among economic sectors in the Czech Republic, with about 11.4 % of all occupational diseases in 2009. Skin diseases constituted about 20 % of all occupational diseases. The aim of this study was to analyze the causes and trends in allergic and irritant-induced skin diseases in the healthcare sector. The data concerning occupational skin diseases (Chapter IV of the Czech List of Occupational Diseases, non-infectious skin illnesses) in the healthcare sector were analyzed from the Czech National Registry of Occupational Diseases from 1997 until 2009. The trends in the total counts and most frequent causes were evaluated. During the past 13 years, a total of 545 skin diseases were acknowledged in healthcare workers. Allergic contact dermatitis was diagnosed in 464 (85 %), irritant contact dermatitis in 71 (13 %) and contact urticaria in 10 subjects (2 %). Ninety-five percent of the patients were females. The overall incidence in individual years varied between 1.0 and 2.9 cases per 10,000 full-time employees per year. Disinfectants were the most frequent chemical agents causing more than one third of all allergic skin diseases (38 %), followed by rubber components (32 %) and cleaning agents (10 %). A general downward trend of diagnosed cases of occupational skin diseases in heath care workers in the Czech Republic over the past 13 years was demonstrated.

Primary irritant and delayed-contact hypersensitivity reactions to the freshwater cyanobacterium Cylindrospermopsis raciborskii and its associated toxin cylindrospermopsin

PubMed Central

Stewart, Ian; Seawright, Alan A; Schluter, Philip J; Shaw, Glen R

2006-01-01

Background Freshwater cyanobacteria are common inhabitants of recreational waterbodies throughout the world; some cyanobacteria can dominate the phytoplankton and form blooms, many of which are toxic. Numerous reports in the literature describe pruritic skin rashes after recreational or occupational exposure to cyanobacteria, but there has been little research conducted on the cutaneous effects of cyanobacteria. Using the mouse ear swelling test (MEST), we sought to determine whether three toxin-producing cyanobacteria isolates and the purified cyanotoxin cylindrospermopsin produced delayed-contact hypersensitivity reactions. Methods Between 8 and 10 female Balb/c mice in each experiment had test material applied to depilated abdominal skin during the induction phase and 10 or 11 control mice had vehicle only applied to abdominal skin. For challenge (day 10) and rechallenge (day 17), test material was applied to a randomly-allocated test ear; vehicle was applied to the other ear as a control. Ear thickness in anaesthetised mice was measured with a micrometer gauge at 24 and 48 hours after challenge and rechallenge. Ear swelling greater than 20% in one or more test mice is considered a positive response. Histopathology examination of ear tissues was conducted by independent examiners. Results Purified cylindrospermopsin (2 of 9 test mice vs. 0 of 5 control mice; p = 0.51) and the cylindrospermopsin-producing cyanobacterium C. raciborskii (8 of 10 test mice vs. 0 of 10 control mice; p = 0.001) were both shown to produce hypersensitivity reactions. Irritant reactions were seen on abdominal skin at induction. Two other toxic cyanobacteria (Microcystis aeruginosa and Anabaena circinalis) did not generate any responses using this model. Histopathology examinations to determine positive and negative reactions in ear tissues showed excellent agreement beyond chance between both examiners (κ = 0.83). Conclusion The irritant properties and cutaneous sensitising potential of

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

PubMed

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

2015-10-01

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

Waveform difference between skin conductance and skin potential responses in relation to electrical and evaporative properties of skin.

PubMed

Tronstad, Christian; Kalvøy, Håvard; Grimnes, Sverre; Martinsen, Ørjan G

2013-11-01

The shapes of skin conductance (SC) and skin potential (SP) responses are often similar, but can also be very different due to an unexplained cause. Using a new method to measure SC and SP simultaneously at the same electrode, this difference was investigated in a new way by comparing their temporal peak differences. SC, SP, skin susceptance (SS), and transepidermal water loss (TEWL) were recorded from 40 participants during relaxation and stress. The SP response could peak anywhere between the onset of an SC response to some time after the peak of an SC response. This peak time difference was associated with the magnitude of the SCR, the hydration of the skin, and the filling of the sweat ducts. Interpretation of the results in light of existing biophysical theories suggests that this peak difference may indicate the hydraulic capacity state of the sweat ducts at the time of a response. Copyright © 2013 Society for Psychophysiological Research.

The Effect of Liquid Gun Propellant (LGP) on Skin.

DTIC Science & Technology

1992-02-27

sodium lauryl sulfate ) decreased the barrier properties of hairless guinea pig skin to the greatest extent after I day, and the barrier returned to normal...San Francisco, CA. Wilhelm K.-P., Surber, C. and Maibach, H.I. Effect of sodium lauryl sulfate - induced skin irritation on in vivo percutaneous...NJ), followed by an intravenous injection of sodium pentobarbital (18 mg/kg, Anthony Products, Arcadia, CA). A Padgett Electro Dermatome (Padgett

Evaluation of self-reported skin problems among workers exposed to toluene diisocyanate (TDI) at a foam manufacturing facility.

PubMed

Daftarian, Helga S; Lushniak, Boris D; Reh, Christopher M; Lewis, Daniel M

2002-12-01

Toluene diisocyanate, or TDI (CAS 584-84-9) is a well-known asthmagen and respiratory irritant. TDI is also known for its ability to irritate the skin and mucous membranes. To further investigate the dermal effects of TDI, NIOSH investigators conducted a cross-sectional study at a flexible foam manufacturing plant. A total of 114 workers participated in the study. Participants completed a medical questionnaire, provided blood for antibody testing to TDI and other allergens, and a subset of participants reporting skin symptoms underwent skin patch testing to a standard diisocyanate panel. Production line workers were more than twice as likely to report skin problems as those working in nonproduction areas (PRR = 2.66; 95% CI = 1.14-16.32; P = 0.02). Age, gender and duration of employment at the plant were comparable among participants working in production and nonproduction areas. Of the 100 participants who provided blood samples for antibody testing, specific IgG antibody to TDI was detected in two individuals, and none of the samples demonstrated specific IgE antibody to TDI. Of the 26 workers who underwent skin patch testing, none developed reactions to the diisocyanate allergens. These results suggest that the skin symptoms among study participants represent an irritant rather than an immunologic reaction to TDI, or to an unidentified allergen present in the foam.

Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

PubMed

Ha, Michael A; Smith, Gregory J; Cichocki, Joseph A; Fan, Lu; Liu, Yi-Shiuan; Caceres, Ana I; Jordt, Sven Eric; Morris, John B

2015-01-01

Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking

Menthol Attenuates Respiratory Irritation and Elevates Blood Cotinine in Cigarette Smoke Exposed Mice

PubMed Central

Ha, Michael A.; Smith, Gregory J.; Cichocki, Joseph A.; Fan, Lu; Liu, Yi-Shiuan; Caceres, Ana I.; Jordt, Sven Eric; Morris, John B.

2015-01-01

Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol’s effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking

The Ex Vivo Eye Irritation Test as an alternative test method for serious eye damage/eye irritation.

PubMed

Spöler, Felix; Kray, Oya; Kray, Stefan; Panfil, Claudia; Schrage, Norbert F

2015-07-01

Ocular irritation testing is a common requirement for the classification, labelling and packaging of chemicals (substances and mixtures). The in vivo Draize rabbit eye test (OECD Test Guideline 405) is considered to be the regulatory reference method for the classification of chemicals according to their potential to induce eye injury. In the Draize test, chemicals are applied to rabbit eyes in vivo, and changes are monitored over time. If no damage is observed, the chemical is not categorised. Otherwise, the classification depends on the severity and reversibility of the damage. Alternative test methods have to be designed to match the classifications from the in vivo reference method. However, observation of damage reversibility is usually not possible in vitro. Within the present study, a new organotypic method based on rabbit corneas obtained from food production is demonstrated to close this gap. The Ex Vivo Eye Irritation Test (EVEIT) retains the full biochemical activity of the corneal epithelium, epithelial stem cells and endothelium. This permits the in-depth analysis of ocular chemical trauma beyond that achievable by using established in vitro methods. In particular, the EVEIT is the first test to permit the direct monitoring of recovery of all corneal layers after damage. To develop a prediction model for the EVEIT that is comparable to the GHS system, 37 reference chemicals were analysed. The experimental data were used to derive a three-level potency ranking of eye irritation and corrosion that best fits the GHS categorisation. In vivo data available in the literature were used for comparison. When compared with GHS classification predictions, the overall accuracy of the three-level potency ranking was 78%. The classification of chemicals as irritating versus non-irritating resulted in 96% sensitivity, 91% specificity and 95% accuracy. 2015 FRAME.

Evaluation of SARs for the prediction of eye irritation/corrosion potential: structural inclusion rules in the BfR decision support system.

PubMed

Tsakovska, I; Saliner, A Gallegos; Netzeva, T; Pavan, M; Worth, A P

2007-01-01

The proposed REACH regulation within the European Union (EU) aims to minimise the number of laboratory animals used for human hazard and risk assessment while ensuring adequate protection of human health and the environment. One way to achieve this goal is to develop non-testing methods, such as (quantitative) structure-activity relationships ([Q]SARs), suitable for identifying toxicological hazard from chemical structure and physicochemical properties alone. A database containing data submitted within the EU New Chemicals Notification procedure was compiled by the German Bundesinstitut für Risikobewertung (BfR). On the basis of these data, the BfR built a decision support system (DSS) for the prediction of several toxicological endpoints. For the prediction of eye irritation and corrosion potential, the DSS contains 31 physicochemical exclusion rules evaluated previously by the European Chemicals Bureau (ECB), and 27 inclusion rules that define structural alerts potentially responsible for eye irritation and/or corrosion. This work summarises the results of a study carried out by the ECB to assess the performance of the BfR structural rulebase. The assessment included: (a) evaluation of the structural alerts by using the training set of 1341 substances with experimental data for eye irritation and corrosion; and (b) external validation by using an independent test set of 199 chemicals. Recommendations are made for the further development of the structural rules in order to increase the overall predictivity of the DSS.

Interventions for preventing occupational irritant hand dermatitis.

PubMed

Bauer, Andrea; Rönsch, Henriette; Elsner, Peter; Dittmar, Daan; Bennett, Cathy; Schuttelaar, Marie-Louise A; Lukács, Judit; John, Swen Malte; Williams, Hywel C

2018-04-30

Occupational irritant hand dermatitis (OIHD) causes significant functional impairment, disruption of work, and discomfort in the working population. Different preventive measures such as protective gloves, barrier creams and moisturisers can be used, but it is not clear how effective these are. This is an update of a Cochrane review which was previously published in 2010. To assess the effects of primary preventive interventions and strategies (physical and behavioural) for preventing OIHD in healthy people (who have no hand dermatitis) who work in occupations where the skin is at risk of damage due to contact with water, detergents, chemicals or other irritants, or from wearing gloves. We updated our searches of the following databases to January 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLlNE, and Embase. We also searched five trials registers and checked the bibliographies of included studies for further references to relevant trials. We handsearched two sets of conference proceedings. We included parallel and cross-over randomised controlled trials (RCTs) which examined the effectiveness of barrier creams, moisturisers, gloves, or educational interventions compared to no intervention for the primary prevention of OIHD under field conditions. We used the standard methodological procedures expected by Cochrane. The primary outcomes were signs and symptoms of OIHD developed during the trials, and the frequency of treatment discontinuation due to adverse effects. We included nine RCTs involving 2888 participants without occupational irritant hand dermatitis (OIHD) at baseline. Six studies, including 1533 participants, investigated the effects of barrier creams, moisturisers, or both. Three studies, including 1355 participants, assessed the effectiveness of skin protection education on the prevention of OIHD. No studies were eligible that investigated the effects of protective gloves. Among each type of intervention, there was heterogeneity concerning

Skin Health Connected to the Use of Absorbent Hygiene Products: A Review.

PubMed

Bender, Johanna Karlsson; Faergemann, Jan; Sköld, Maria

2017-09-01

Over the past 50 years, absorbent hygiene products such as baby diapers and incontinence products have become essential features of modern day life. Through innovation and enhanced technology, their design, composition and performance have been dramatically upgraded from their early forms, and they have transformed the lives of millions of people, improving their quality of life. Skin health related to the use of absorbent hygiene products has accordingly also greatly improved. Still, the wearing of absorbent hygiene products will affect the skin, and for some users the changes in microclimate, mechanical interactions and the exposure to urine and faeces may result in irritant contact dermatitis, i.e. diaper dermatitis (DD) or incontinence-associated dermatitis (IAD). Babies with developing skin and the elderly with deteriorating skin functions who are the most frequent users of absorbent hygiene products are more vulnerable to the causal factors. Although irritant reactions are the most common, allergic contact dermatitis should be considered if a DD/IAD fails to improve by recommended actions. There is also a connection between IAD and pressure ulcer development of which it is important to be aware. A holistic approach of using high-quality absorbent hygiene products in combination with appropriate skin care will help maintaining good skin health.

Instrument-related Skin Disorders in Musicians.

PubMed

Patruno, Cataldo; Napolitano, Maddalena; La Bella, Serena; Ayala, Fabio; Balato, Nicola; Cantelli, Mariateresa; Balato, Anna

2016-01-01

Among artists, musicians may suffer from occupational skin problems; notwithstanding, these conditions have been rarely reviewed. The characteristics of individual performer and the type of instrument will determine the kind of disease. Moreover, the hours that the musician spent to advance artistic skill may influence the severity. The frequency and risk factors of instrument-related skin disorders in musicians from southern Italy were analyzed. An observational study was conducted in 628 musicians. A questionnaire including questions related to age, sex, instrument played, musical activity, previous or current skin disorders, and impact of skin symptoms on music making was submitted. Of 628 musicians, 199 (31.7%) reported suffering from at least 1 skin disease. Cutaneous diseases likely directly correlated with the use of the musical instrument were found in 129 (20.5%) of the 628 subjects. In particular, different patterns of irritant contact dermatitis were found. Skin conditions may be a significant problem in professional instrumentalists. They are mainly related to musical activity. Preventive measures should be established.

Irritant contact dermatitis caused by needle-like calcium oxalate crystals, raphides, in Agave tequilana among workers in tequila distilleries and agave plantations.

PubMed

Salinas, M L; Ogura, T; Soffchi, L

2001-02-01

It was found that needle-like calcium oxalate crystals, raphides, are found abundantly in all tissues of Agave tequilana plants; thus, 1 droplet (0.03 ml) of juice pressed from leaves contains 100-150 crystals, 30-500 microm in length, sharpened at both ends. In tequila distilleries, 5/6 of the workers who handle the agave stems have experienced the characteristic irritation. In contrast, only 1/3 of workers in agave plantations who harvest agave plants, complain of the irritation. It is confirmed that all the irritation suffered in both distilleries and plantations takes place at bodily locations where the plants come into contact with the worker's skin in the course of their work.

Competition between skin-sensitizing chemicals in the mouse

PubMed Central

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

1974-01-01

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

"The fairer the better?" Use of potentially toxic skin bleaching products.

PubMed

Darj, Elisabeth; Infanti, Jennifer J; Ahlberg, Beth Maina; Okumu, Jecinta

2015-12-01

Skin bleaching is a widespread phenomenon in spite of their potentially toxic health effects. This study aimed to determine if such products are used in Sweden in particular by pregnant women, furthermore to explore immigrant women's view skin bleaching. 455 pregnant women completed a questionnaire, which were statistically analysed. Focus groups and individual interviews were conducted with immigrant women, content analysis was used to assess the data. Skin bleaching products were used by 2.6% of pregnant women, significantlly more by women born in non-European countries. Motivating factors were associated with the concept of beauty together with social and economic advantages. The women had low awareness of the potential health risks of the products. Regulations on the trade of skin bleaching products have not effectively reduced the availability of the products in Sweden nor the popularity of skin bleaching. There is need for further research especially among pregnant women and possible effects on newborns. Products should be tested for toxicity. Public health information should be developed and health care providers educated and aware of this practice, due to their potential negative health implications.

CON4EI: EpiOcular™ Eye Irritation Test (EpiOcular™ EIT) for hazard identification and labelling of eye irritating chemicals.

PubMed

Kandarova, H; Letasiova, S; Adriaens, E; Guest, R; Willoughby, J A; Drzewiecka, A; Gruszka, K; Alépée, Nathalie; Verstraelen, Sandra; Van Rompay, An R

2018-06-01

Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. The objective of the CON4EI project was to develop tiered testing strategies for eye irritation assessment. A set of 80 reference chemicals (38 liquids and 42 solids) was tested with eight different methods. Here, the results obtained with the EpiOcular™ Eye Irritation Test (EIT), adopted as OECD TG 492, are shown. The primary aim of this study was to evaluate of the performance of the test method to discriminate between chemicals not requiring classification for serious eye damage/eye irritancy (No Category) and chemicals requiring classification and labelling. In addition, the predictive capacity in terms of in vivo drivers of classification (i.e. corneal opacity, conjunctival redness and persistence at day 21) was investigated. EpiOcular™ EIT achieved a sensitivity of 97%, a specificity of 87% and accuracy of 95% and also confirmed its excellent reproducibility (100%) from the original validation. The assay was applicable to all chemical categories tested in this project and its performance was not limited to the particular driver of the classification. In addition to the existing prediction model for dichotomous categorization, a new prediction model for Cat 1 is suggested. Copyright © 2017. Published by Elsevier Ltd.

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.

Evaluation of the Potential Risk of Hepatitis B Virus Transmission in Skin Allografting.

PubMed

Wang, D; Xie, W; Chen, T; Dong, C; Zhao, C; Tan, H; Tian, H; Xie, Q

2015-01-01

Skin transplantation is associated with potential risk of infectious disease transmission; however, the exclusion of donors owing to hepatitis B virus (HBV) infection will worsen the shortage of allograft skin supply. We report a paired study to evaluate the potential risk of HBV transmission in skin allografting. The presence of HBV DNA in the serum and skin from 37 burn patients with chronic HBV infection (CHB) was monitored by a HBV polymerase chain reaction (PCR) and the positive rates were compared by Fisher's exact probability test. There was a high consistency in the HBV serology profile between HBV DNA PCR (83.78%) and the clinical HBV test. Only 2 patients who were positive for hepatitis B surface antigen, hepatitis B e antigen, and hepatitis B core antibody had detectable HBV DNA in the skin tissue; however, no hepatitis B surface antigen was detected as examined by immunohistochemistry staining. There was a significant difference between the positive rates of HBV DNA in the serum and skin (χc(2) = 27.03; P < .001). The potential risk for HBV transmission by skin allografting is very low. Given that China has a large population of patients with HBV, the acceptance of skin from donors with CHB to the skin bank would increase the number of tissue donations to meet the urgent medical need for skin transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

Topical absorption and toxicity studies of jet fuel hydrocarbons in skin

NASA Astrophysics Data System (ADS)

Muhammad, Faqir

Kerosene-based fuels have been used for many decades. Over 2 million military and civilian personnel each year are occupationally exposed to various jet fuel mixtures. Dermatitis is one of the major health concerns associated with these exposures. In the past, separate absorption and toxicity studies have been conducted to find the etiology of such skin disorders. There was a need for integrated absorption and toxicity studies to define the causative constituents of jet fuel responsible for skin irritation. The focus of this thesis was to study the percutaneous absorption and to identify the hydrocarbons (HC) causing irritation in jet fuels so that preventive measures could be taken in the future. The initial study was conducted to understand the possible mechanism for additive interactions on hydrocarbon absorption/disposition in silastic, porcine skin and isolated perfused porcine skin flap (IPPSF) models. The influence of JP-8 (100) additives (MDA, BHT, 8Q405) on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of HC absorption was evaluated. This study indicated that individual and combination of additives influenced marker disposition in different membranes. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption in IPPSF. The 8Q405 significantly reduced naphthalene content in dosed silastic and skin indicating a direct interaction between additive and marker HC. Similarly, the individual MDA and BHT significantly retained naphthalene in the stratum corneum of porcine skin, but the combination of both of these additives statistically decreased the marker retention in the stratum corneum suggesting a potential biological interaction. This study concluded that all components of a chemical mixture should be assessed since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture. However, this study indicated that the marker HC

Evaluating skin care problems in people with stomas.

PubMed

Williams, Julia; Gwillam, Brandon; Sutherland, Norma; Matten, Jane; Hemmingway, Julie; Ilsey, Helen; Somerville, Mary; Vujnovich, Angela; Day, Stephanie; Redmond, Caroline; Cowin, Caroline; Fox, Kathy; Parker, Theresa

This study aimed to identify actual and potential peristomal skin problems in relation to the use of different types of stoma appliances and accessories. It also compared ostomists' perceptions of their peristomal skin condition with those of stoma care nurse specialists. Maintaining skin integrity is a basic skill that ensures good stoma management. It is widely accepted that from time to time a patient with a stoma will seek clinical advice about a peristomal skin problem. Little is known about how often patients present with these problems, the clinical course of peristomal skin problems, and how patients manage them. A multi-centred descriptive study was conducted among 80 ostomists. Fieldwork took place over 13 months. The sample was drawn from a UK home care delivery database. Using structured questionnaires, ostomists were interviewed by a stoma care nurse specialist. A digital photograph was taken of their peristomal skin and their answers compared with nurse assessment using the Stoma Care Ostomy Research index scoring system. Of the interviewees 32% had healthy peristomal skin both via questionnaire and at observation. At observation, 68% were observed to have peristomal skin problems, of whom 44% had irritated skin, 12% had ulcerated skin, 9% had an apparent allergy and 3% had macerated/eroded skin. In addition, 21% had an ill-fitting appliance at observation. Half (50%) were observed to have a parastomal hernia, although only 24% reported having one. These findings demonstrate significant differences between the perception of skin problems among ostomists and actual skin problems observed by stoma care nurse specialists. Peristomal skin problems are common among ostomists. The difference between ostomists' and nurses' perceptions of peristomal skin condition led to the identification of educational needs for the new ostomist. Education and regular follow-up by the stoma care nurse specialist is imperative.

Effects of JP-8 on Molecular and Histological Parameters Related to Acute Skin Irritation

DTIC Science & Technology

2000-06-01

in irritant dermatitis are understood. Cytokines are cell signaling molecules that are involved in the inflammatory response. These include the...are involved in inflammatory responses in contact dermatitis (Figure 2, Ormerod et al., 1997). The analysis of iNOS mRNA or protein, as well as the...placed into a Bessman steel tissue pulverizer (Fisher Scientific, Cat # 08-418-2) that was pre-chilled in liquid nitrogen. Using a lead hammer

The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders

PubMed Central

Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

2016-01-01

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract. PMID:26901191

The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders.

PubMed

Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

2016-02-18

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.

Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests.

PubMed

Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

2015-09-01

The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%).

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

PubMed

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

2016-10-01

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

Development of an in vitro alternative assay method for vaginal irritation.

PubMed

Ayehunie, Seyoum; Cannon, Chris; Larosa, Karen; Pudney, Jeffrey; Anderson, Deborah J; Klausner, Mitchell

2011-01-11

The vaginal mucosa is commonly exposed to chemicals and therapeutic agents that may result in irritation and/or inflammation. In addition to acute effects, vaginal irritation and inflammation can make women more susceptible to infections such as HIV-1 and herpes simplex virus 2 (HSV-2). Hence, the vaginal irritation potential of feminine care formulations and vaginally administered therapeutic agents is a significant public health concern. Traditionally, testing of such materials has been performed using the rabbit vaginal irritation (RVI) assay. In the current study, we investigated whether the organotypic, highly differentiated EpiVaginal™ tissue could be used as a non-animal alternative to the RVI test. The EpiVaginal tissue was exposed to a single application of ingredients commonly found in feminine hygiene products and the effects on tissue viability (MTT assay), barrier disruption (measured by transepithelial electrical resistance, TEER and sodium fluorescein (NaFl) leakage), and inflammatory cytokine release (interleukin (IL)-1α, IL-1β, IL-6, and IL-8) patterns were examined. When compared to untreated controls, two irritating ingredients, nonoxynol 9 and benzalkonium chloride, reduced tissue viability to <40% and TEER to <60% while increasing NaFl leakage by 11-24% and IL-1α and IL-1β release by >100%. Four other non-irritating materials had minimal effects on these parameters. Assay reproducibility was confirmed by testing the chemicals using three different tissue production lots and by using tissues reconstructed from cells obtained from three different donors. Coefficients of variation between tissue lots reconstructed with cells obtained from the same donor or lots reconstructed with cells obtained from different donors were less than 10% and 12%, respectively. In conclusion, decreases in tissue viability and barrier function and increases in IL-1α and IL-1β release appear to be useful endpoints for preclinical screening of topically applied

THE USE OF SILICONES TO PROTECT THE SKIN

PubMed Central

Morrow, Grant

1954-01-01

Silicote® ointment was used as a protective covering for the skin in the treatment of 107 patients with various kinds of dermatologic disease. In 83 the disease was cured or effectively controlled. It was particularly effective in conditions caused or aggravated by water-soluble or oil-soluble irritants. PMID:13116024

Oral intake of beet extract provides protection against skin barrier impairment in hairless mice.

PubMed

Kawano, Ken-Ichi; Umemura, Kazuo

2013-05-01

The epidermis acts as a functional barrier against the external environment. Disturbances in the function of this barrier cause water loss and increase the chances of penetration by various irritable stimuli, leading to skin diseases such as dry skin, atopic dermatitis, and psoriasis. Ceramides are a critical natural element of the protective epidermal barrier. The aim of this study was to evaluate whether the oral intake of beet (Beta vulgaris) extract, a natural product rich in glucosylceramide (GlcCer), may prevent disturbance in skin barrier function. When HR-1 hairless mice were fed a special diet (HR-AD), transepidermal water loss (TEWL) from the dorsal skin increased, with a compensatory increase in water intake after 5 weeks. Mice fed with HR-AD had dry skin with erythema and showed increased scratching behaviour. Histological examinations revealed a remarkable increase in the thickness of the skin at 8 weeks. Supplemental addition of beet extract, which contained GlcCer at a final concentration of 0.1%, significantly prevented an increase TEWL, water intake, cumulative scratching time, and epidermal thickness at 8 weeks. These results indicate that oral intake of beet extract shows potential for preventing skin diseases associated with impaired skin barrier function. Copyright © 2012 John Wiley & Sons, Ltd.

Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests

PubMed Central

Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

2014-01-01

The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%). PMID:27134543

Comparison of in vitro eye irritation potential by bovine corneal opacity and permeability (BCOP) assay to erythema scores in human eye sting test of surfactant-based formulations.

PubMed

Cater, Kathleen C; Harbell, John W

2008-01-01

The bovine corneal opacity and permeability (BCOP) assay can be used to predict relative eye irritation potential of surfactant-based personal care formulations relative to a corporate benchmark. The human eye sting test is typically used to evaluate product claims of no tears/no stinging for children's bath products. A preliminary investigation was conducted to test a hypothesis that the BCOP assay could be used as a prediction model for relative ranking of human eye irritation responses under conditions of a standard human eye sting test to surfactant-based formulations. BCOP assays and human eye sting tests were conducted on 4 commercial and 1 prototype body wash (BW) developed specifically for children or as mild bath products. In the human eye sting test, 10 mul of a 10% dosing solution is instilled into one eye of each panelist (n = 20), and the contralateral eye is dosed with sterile water as a control. Bulbar conjunctival erythema responses of each eye are graded at 30 seconds by an ophthalmologist. The BCOP assay permeability values (optical density at 490 nm [OD(490)]) for the 5 BWs ranged from 0.438 to 1.252 (i.e., least to most irritating). By comparison, the number of panelists exhibiting erythema responses (mild to moderately pink) ranged from 3 of 20 panelists for the least irritating BW to 10 of 20 panelists for the most irritating BW tested. The relative ranking of eye irritation potential of the 5 BWs in the BCOP assay compares favorably with the relative ranking of the BWs in the human eye sting test. Based on these findings, the permeability endpoint of the BCOP assay, as described for surfactant-based formulations, showed promise as a prediction model for relative ranking of conjunctival erythema responses in the human eye. Consequently, screening of prototype formulations in the BCOP assay would allow for formula optimization of mild bath products prior to investment in a human eye sting test.

Skin problems in stoma patients.

PubMed

Nybaek, H; Jemec, G B E

2010-03-01

Ostomy patients are dependent on the integrity of their peristomal skin to maintain a normal lifestyle. Peristomal skin problems are thought to be common and may interfere with the use of ostomy pouching systems. This is a specialist area not commonly seen by dermatologists. This article seeks to provide an overview of the topic for the general dermatologist. A systematic literature search was conducted. The articles found were reviewed and relevant articles were selected by two investigators. Loss of skin integrity may be related to chemical injury, mechanical destruction, infectious conditions, immunological reactions, disease-related conditions. Peristomal irritant dermatitis caused by skin contact with ostomy effluent is by far the most ordinary condition seen. Mechanical trauma, infection and aggravation of pre-existing skin diseases are also seen. Allergic contact dermatitis, which is often cited as the cause of peristomal skin problems, appears to be a rare condition with an estimated prevalence of only 0.6%. In spite of the importance of the integrity of peristomal skin, the topic is poorly described in the literature. The existing publications suggest that although peristomal skin disease can be diagnosed and treated, additional information on both patients and physicians is necessary to optimize patient care.

Evaluation of a three-dimensional human dermal model as a predictor of shampoo ocular irritation.

PubMed

Decker, D; Harper, R

1994-04-01

A three-dimensional human tissue model (Skin(2) ZK1100) was used to evaluate 43 adult and baby shampoos. The ZK1100 model consists of metabolically active proliferating human fibroblasts isolated from the dermis of neonatal foreskins and seeded onto a nylon mesh. The fibroblasts multiply and produce matrix proteins to form a living tissue. MTT reduction (mitochondrial function) was used as the cytotoxicity endpoint. The primary components of the adult shampoos are alkyl sulfate surfactants, while the baby shampoos contain ethoxylated alkyl sulfates and amphoteric surfactants. All shampoos were diluted to five concentrations (100, 300, 700, 1000 and 3000 mug/ml) in aqueous cell culture media and the tissue exposed for 24 hr. An EC(50) value for each test was generated from a dose-response curve. All samples were tested in two or more separate experiments, and the EC(50) values were averaged and plotted versus their respective 24-hr unwashed Draize eye irritation values (r(2) = 0.81). The adult shampoos had Draize values in the moderate irritation category and EC(50) values ranging from 220 to 1051 mug/ml, while the baby shampoos had Draize values in the minimal irritation category and EC(50) values ranging from 820 to 2285 mug/ml. These results indicate that the three-dimensional human tissue model can be useful in predicting the Draize ocular irritation category for shampoos.

Occupational skin problems in construction workers.

PubMed

Shah, Kartik R; Tiwari, Rajnarayan R

2010-10-01

Construction workers handle cement which has constituents to produce both irritant contact dermatitis and corrosive effects (from alkaline ingredients, such as lime) and sensitization, leading to allergic contact dermatitis (from ingredients, such as chromium). The present study has been carried out among unorganized construction workers to find the prevalence of skin problems. The present cross-sectional study was conducted in 92 construction workers of Ahmedabad and Vadodara. All the workers were subjected to clinical examination after collection of information regarding demographic characteristics, occupational characteristics and clinical history on a predesigned proforma. Of them, 47.8% had morbid skin conditions. Frictional callosities in palm were observed in 18 (19.6%) subjects while 4 (4.3%) subjects had contact dermatitis. Other conditions included dry, fissured and scaly skin, infectious skin lesion, tinea cruris, lesion and ulcers on hands and/or soles. The skin conditions were common in the age group of 20-25 years, males, those having ≥1 year exposure and those working for longer hours. Half of the workers not using personal protective equipment had reported skin-related symptoms.

[Methaemoglobinaemia and respiratory tract irritation connected with poppers inhalation].

PubMed

Łukasik-Głebocka, Magdalena; Matuszkiewicz, Eryk

2010-01-01

"Poppers" is the street name for volatile nitrites offered by online shops and sex-shops for their aphrodisiac and euphoric properties. Although nitrites have been abused since the late 1960s, recently they became popular in Poland. Recreational poppers using was associated with homosexual men at first. Currently they are commonly reported among heterosexual men and regular dicso participants. Advertisements of these substances tempt potential buyers with the promise of a legal narcotic high. Easy access and the sense of safety make these products the reason of acute toxicity. Volatile nitrites relaxes smooth muscle, the consequent intense peripheral vasodilatation produces flushing, a fall in blood pressure, and reflex increase in heart rate. These effects are accompanied by feeling of warmth, euphoria and intensifying of sexual pleasure. Serious poisoning results in severe methaemoglobinaemia, coma, respiratory and cardiovascular failure, and even death. Skin and mucous contact with poppers can produce a crusty lesion at the site. This article presents the case of 44-years old male hospitalized three times in Toxicology Department after history of poppers abusing. Methaemoglobinaemia (26.4%) and tracheobronchial irritation were the main symptoms observed. Patient was given specific therapy with methylene blue.

Pigmented and hyperkeratotic napkin dermatitis: a liquid detergent irritant dermatitis.

PubMed

Patrizi, A; Neri, I; Marzaduri, S; Fiorillo, L

1996-01-01

Napkin or diaper dermatitis (DD) is an inflammatory cutaneous eruption limited to the diaper area and common in the first 2 years of life. A number of clinical variants of DD have been identified. We report a new variant of DD characterized by papyraceous skin, brownish discoloration and predilection for the depth of folds. 15 infants and toddlers affected by this peculiar type of DD were evaluated regarding duration, localization, morphology and evolution of their dermatosis. This variant of DD was mainly confined to the depth of inguinal and gluteal folds and invariably associated with severe xerosis with papyraceous and glazed skin. The patients were healthy and asymptomatic and all laboratory investigations performed were normal. All patients were frequently changed and thoroughly washed with synthetic detergents with acid pH. DD improved rapidly with reduced frequency of washing and discontinuation of liquid detergents. We conclude that this condition is a type of irritant contact dermatitis from excessive use of lipid acid detergents.

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin.

PubMed

Kim, Eun Ju; Lee, Dong Hun; Kim, Yeon Kyung; Kim, Min-Kyoung; Kim, Jung Yun; Lee, Min Jung; Choi, Won Woo; Eun, Hee Chul; Chung, Jin Ho

2014-12-01

Sensitive skin represents hyperactive sensory symptoms showing exaggerated reactions in response to internal stimulants or external irritants. Although sensitive skin is a very common condition affecting an estimated 50% of the population, its pathophysiology remains largely elusive, particularly with regard to its metabolic aspects. The objective of our study was to investigate the pathogenesis of sensitive skin. We recruited healthy participants with 'sensitive' or 'non-sensitive' skin based on standardized questionnaires and 10% lactic acid stinging test, and obtained skin samples for microarray analysis and subsequent experiments. Microarray transcriptome profiling revealed that genes involved in muscle contraction, carbohydrate and lipid metabolism, and ion transport and balance were significantly decreased in sensitive skin. These altered genes could account for the abnormal muscle contraction, decreased ATP amount in sensitive skin. In addition, pain-related transcripts such as TRPV1, ASIC3 and CGRP were significantly up-regulated in sensitive skin, compared with non-sensitive skin. Our findings suggest that sensitive skin is closely associated with the dysfunction of muscle contraction and metabolic homeostasis. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Professors' Irritating Behavior Study

ERIC Educational Resources Information Center

Malikow, Max

2007-01-01

The purpose of this study was to quantify the irritating behaviors of professors as experienced and reported by 232 Le Moyne College students. In this study, "irritating behavior" was understood as "actions that vex, annoy, bother, pester, frustrate, or provoke anger." The survey used in this study was developed by Larry M. Ludewig, Ph.D.,…

Estimation of the chemical-induced eye injury using a weight-of-evidence (WoE) battery of 21 artificial neural network (ANN) c-QSAR models (QSAR-21): part I: irritation potential.

PubMed

Verma, Rajeshwar P; Matthews, Edwin J

2015-03-01

Evaluation of potential chemical-induced eye injury through irritation and corrosion is required to ensure occupational and consumer safety for industrial, household and cosmetic ingredient chemicals. The historical method for evaluating eye irritant and corrosion potential of chemicals is the rabbit Draize test. However, the Draize test is controversial and its use is diminishing - the EU 7th Amendment to the Cosmetic Directive (76/768/EEC) and recast Regulation now bans marketing of new cosmetics having animal testing of their ingredients and requires non-animal alternative tests for safety assessments. Thus, in silico and/or in vitro tests are advocated. QSAR models for eye irritation have been reported for several small (congeneric) data sets; however, large global models have not been described. This report describes FDA/CFSAN's development of 21 ANN c-QSAR models (QSAR-21) to predict eye irritation using the ADMET Predictor program and a diverse training data set of 2928 chemicals. The 21 models had external (20% test set) and internal validation and average training/verification/test set statistics were: 88/88/85(%) sensitivity and 82/82/82(%) specificity, respectively. The new method utilized multiple artificial neural network (ANN) molecular descriptor selection functionalities to maximize the applicability domain of the battery. The eye irritation models will be used to provide information to fill the critical data gaps for the safety assessment of cosmetic ingredient chemicals. Copyright © 2014 Elsevier Inc. All rights reserved.

Irritability and Anxiety Severity Among Youth With Anxiety

PubMed Central

Cornacchio, Danielle; Crum, Kathleen I.; Coxe, Stefany; Pincus, Donna B.; Comer, Jonathan S.

2015-01-01

Objective Most research on irritability and child psychopathology has focused on depressive disorders, bipolar disorder, and/or oppositional defiant disorder (ODD). Less is known about relationships between child anxiety and irritability and moderators of such associations. Method Structural equation modeling (SEM) examined associations between anxiety severity and irritability in a large sample of treatment-seeking youth with anxiety disorders (N=663, ages 7–19 years, M=12.25), after accounting for comorbid depressive disorders and ODD. Additional analyses examined whether associations were moderated by child gender, age, and generalized anxiety disorder (GAD) status. Results There was a direct link between child anxiety and irritability even after accounting for comorbid depressive disorders and ODD. Links between child anxiety and irritability were robust across child gender and age. Further, relationships between child anxiety and irritability were comparable across youth with and without GAD, suggesting that the anxiety–irritability link is relevant across child anxiety disorders and not circumscribed to youth with GAD. Conclusion Findings add to an increasing body of evidence linking child irritability to a range of internalizing and externalizing psychopathologies, and suggest that child anxiety assessment should systematically incorporate irritability evaluations. Further, youth in clinical settings displaying irritability should be assessed for the presence of anxiety. Moreover, treatments for childhood anxiety may do well to incorporate new treatment modules as needed that specifically target problems of irritability. PMID:26703910

Genome-wide expression analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulfate and nonanoic acid.

PubMed

Clemmensen, Anders; Andersen, Klaus E; Clemmensen, Ole; Tan, Qihua; Petersen, Thomas K; Kruse, Torben A; Thomassen, Mads

2010-09-01

The pathogenesis of irritant contact dermatitis (ICD) is poorly understood, and genes participating in the epidermal response to chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies ((1/2), 4, and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to either sodium lauryl sulfate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays (representing 47,000 transcripts) revealed essentially different pathway responses (1/2)hours after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen-activated signaling cascades including extracellular signal-regulated kinase and growth factor receptor signaling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed, whereas we identified 23 suggested common biomarkers for ICD. In conclusion, we bring new insights into two hitherto less well-elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative mild exposures, respectively.

Human axillary skin condition is improved following incorporation of glycerol into the stratum corneum from an antiperspirant formulation.

PubMed

Evans, Richard L; Turner, Graham A; Bates, Susan; Robinson, Teresa; Arnold, David; Marriott, Robert E; Pudney, Paul D A; Bonnist, Eleanor Y M; Green, Darren

2017-11-01

The study objectives were to demonstrate that glycerol, when topically applied from a roll-on antiperspirant formulation, can be delivered directly to human skin ex vivo and the axillary stratum corneum (SC) in vivo, and to assess whether it improves the quality of the axillary skin barrier. Ex vivo human skin absorption of glycerol was measured following application of a roll-on antiperspirant formulation containing 4% 13 C 3 -glycerol. Skin distribution of 13 C 3 -glycerol over 24 h was assessed using gas chromatography-mass spectrometry. In vivo axillary SC penetration was measured by confocal Raman spectroscopy and multivariate curve-resolution software 1 h after topical application of a roll-on antiperspirant formulation containing 8% deuterated glycerol (d 5 -glycerol). A clinical study was conducted to determine the efficacy of a roll-on antiperspirant formulation containing 4% glycerol in reducing shaving-induced visual irritation and in increasing axillary-skin hydration. Ex vivo skin absorption studies indicated that the formulation delivered 13 C 3 -glycerol into the SC at all timepoints over the 24-h period. In vivo Raman measurements (1 h after application) demonstrated that d 5 -glycerol was detectable to a depth of at least 10 μm in the axillary SC. Application of 4% glycerol from a roll-on antiperspirant formulation to the axilla was associated with significantly less visible irritation and greater skin hydration than observed with the control (glycerol-free) product. These studies demonstrate that glycerol, incorporated in a roll-on antiperspirant formulation, is delivered directly and rapidly to all depths of the axillary SC, and results in improvements in visible irritation and hydration in the axilla.

Vitrigel-eye irritancy test method using HCE-T cells.

PubMed

Yamaguchi, Hiroyuki; Kojima, Hajime; Takezawa, Toshiaki

2013-10-01

We previously reported that the time-dependent relative changes of transepithelial electrical resistance (TEER) after exposing four different chemicals to a human corneal epithelium (HCE) model were well correlated to the potential of ocular irritancy. Meanwhile, we recently developed a collagen vitrigel membrane (CVM) chamber possessing a scaffold composed of high-density collagen fibrils equivalent to connective tissues in vivo as a three-dimensional culture tool. The CVM chamber is useful for biomedical assays and immunohistology using cryosections that are inappropriate to be performed using the conventional Millicell chamber with a polyethylene terephthalate membrane. In this study, we aimed to develop a new eye irritancy test (EIT) method called "Vitrigel-EIT method" that can facilitate to briefly and accurately estimate the widespread irritancy of test chemicals by applying the TEER assay system to a HCE model fabricated in the CVM chamber. HCE-T cells (a HCE-derived cell strain) were cultured in the CVM chamber for 6 days, and consequently, the Vitrigel-HCE model possessing the following characteristics of HCE in vivo was formed: six cell layers with specific protein expressions and their barrier function. Time-dependent profiles of TEER values after exposing 30 test chemicals to the HCE model were converted into the scores of three indexes (time lag, intensity, and plateau level), and each chemical was successfully classified into irritant or nonirritant category by utilizing the criteria for the indexes, resulting in the excellent correlation with Globally Harmonized System of Classification and Labelling of Chemicals (GHS) classification (sensitivity: 100%, specificity: 75%, accuracy: 90%). These data suggest that the widespread eye irritancy of chemicals can be predicted without false negatives by the Vitrigel-EIT method. Interestingly, the disruption of tight junctions was immunohistologically observed after exposing not only irritants but also three

Effect of estrogens on skin aging and the potential role of SERMs

PubMed Central

Stevenson, Susan; Thornton, Julie

2007-01-01

In humans, structural and functional changes attributable to aging are more visibly evident in the skin than in any other organ. Estrogens have significant effects on skin physiology and modulate epidermal keratinocytes, dermal fibroblasts and melanocytes, in addition to skin appendages including the hair follicle and the sebaceous gland. Importantly, skin aging can be significantly delayed by the administration of estrogen. This paper reviews the effects of estrogens on skin and the mechanisms by which estrogens can alleviate the changes due to aging that occur in human skin. The relevance of estrogen replacement therapy (HRT) in post-menopausal women and the potential value of selective estrogen receptor modulators (SERMs) as a therapy for diminishing skin aging are also highlighted. PMID:18044179

Testing ocular irritancy in vitro with the silicon microphysiometer.

PubMed

Bruner, L H; Miller, K R; Owicki, J C; Parce, J W; Muir, V C

1991-01-01

The silicon microphysiometer, an instrument based on the light-addressable potentiometric sensor, was evaluated as an in vitro alternative for assessing ocular irritancy potential. It indirectly and non-invasively measures cell metabolism by determining the rate of acid metabolite production from cells, in this case human epidermal keratinocytes, placed inside the microphysiometer chamber. The 17 materials used for the evaluation included bar soaps, a liquid hand soap, shampoos, dishwashing liquids, laundry detergents, a fabric softener and several single chemicals. All materials tested were in liquid form. The in vivo irritancy potential of the materials was obtained from historical data using the rabbit low-volume eye test. There was a positive correlation between the in vivo irritancy potential of the test materials and the concentration of test material that decreased the acidification rate of cells by 50% (MRD(50); r = 0.86, P < 0.0001). Preliminary studies suggest other endpoints obtainable from the system may also provide useful information for making ocular safety assessments. Because the method is non-invasive, it is possible to determine whether cells recover from a treatment with the test material. The metabolic rate of the cells also increases at sub-inhibitory concentrations of some of the test materials. Because of the good correlation between the in vivo and in vitro data, the ease with which test materials can be applied to the system, and the multiple endpoints available from the system, it holds great potential as a useful in vitro alternative for ocular safety testing.

Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

PubMed

Shetty, Pallavi Krishna; Manikkath, Jyothsna; Tupally, Karnaker; Kokil, Ganesh; Hegde, Aswathi R; Raut, Sushil Y; Parekh, Harendra S; Mutalik, Srinivas

2017-08-01

The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q 12 ), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

Health impacts of chemical irritants used for crowd control: a systematic review of the injuries and deaths caused by tear gas and pepper spray.

PubMed

Haar, Rohini J; Iacopino, Vincent; Ranadive, Nikhil; Weiser, Sheri D; Dandu, Madhavi

2017-10-19

Chemical irritants used in crowd control, such as tear gases and pepper sprays, are generally considered to be safe and to cause only transient pain and lacrimation. However, there are numerous reports that use and misuse of these chemicals may cause serious injuries. We aimed to review documented injuries from chemical irritants to better understand the morbidity and mortality associated with these weapons. We conducted a systematic review using PRISMA guidelines to identify injuries, permanent disabilities, and deaths from chemical irritants worldwide between January 1, 1990 and March 15, 2015. We reviewed injuries to different body systems, injury severity, and potential risk factors for injury severity. We also assessed region, context and quality of each included article. We identified 31 studies from 11 countries. These reported on 5131 people who suffered injuries, two of whom died and 58 of whom suffered permanent disabilities. Out of 9261 total injuries, 8.7% were severe and required professional medical management, while 17% were moderate and 74.3% were minor. Severe injuries occurred to all body systems, with the majority of injuries impacting the skin and eyes. Projectile munition trauma caused 231 projectile injuries, with 63 (27%) severe injuries, including major head injury and vision loss. Potentiating factors for more severe injury included environmental conditions, prolonged exposure time, and higher quantities of chemical agent in enclosed spaces. Although chemical weapons may have a limited role in crowd control, our findings demonstrate that they have significant potential for misuse, leading to unnecessary morbidity and mortality. A nuanced understanding of the health impacts of chemical weapons and mitigating factors is imperative to avoiding indiscriminate use of chemical weapons and associated health consequences.

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies.

PubMed

Wang, Zheng; Mu, Hong-Jie; Zhang, Xue-Mei; Ma, Peng-Kai; Lian, Sheng-Nan; Zhang, Feng-Pu; Chu, Sheng-Ying; Zhang, Wen-Wen; Wang, Ai-Ping; Wang, Wen-Yan; Sun, Kao-Xiang

2015-01-01

Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil(®), 13.44% Cremophor(®) RH40, 6.72% Labrasol(®), and 5.04% Transcutol(®) HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro(®)). The microemulsion gel irritated the skin less than Neupro. A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability.

Black-spot poison ivy dermatitis. An acute irritant contact dermatitis superimposed upon an allergic contact dermatitis.

PubMed

Hurwitz, R M; Rivera, H P; Guin, J D

1984-08-01

A black spot in the epidermis over a blister of poison ivy dermatitis is an uncommon finding. Four patients with the phenomenon are described. Histologic and histochemical studies were made on biopsy material and the blackish deposit on the skin surface was compared with black deposits in and on leaves of the species of poison ivy. This examination revealed a yellow, amorphous substance on the stratum corneum of the lesions and a similar substance in and on leaves of the poison ivy plant, Toxicodendron radicans ssp. negundo. Associated with the pigmentary deposits there were distinct changes of acute irritant contact dermatitis superimposed upon allergic contact dermatitis. Our findings support the view that the black material is the oleoresin of the plant, and that this substance behaves both as an irritant and an allergen.

Skin care in nursing: A critical discussion of nursing practice and research.

PubMed

Kottner, Jan; Surber, Christian

2016-09-01

Skin (self-)care is part of human life from birth until death. Today many different skin care practices, preferences, traditions and routines exist in parallel. In addition, preventive and therapeutic skin care is delivered in nursing and healthcare by formal and informal caregivers. The aim of this contribution is a critical discussion about skin care in the context of professional nursing practice. An explicit skin assessment using accurate diagnostic statements is needed for clinical decision making. Special attention should be paid on high risk skin areas, which may be either too dry or too moist. From a safety perspective the protection and maintenance of skin integrity should have the highest priority. Skin cleansing is the removal of unwanted substances from the skin surface. Despite cleansing efficacy soap, other surfactants and water will inevitably always result in the destruction of the skin barrier. Thousands of products are available to hydrate, moisturize, protect and restore skin properties dependent upon their formulation and the concentration of ingredients. These products intended to left in contact with skin exhibit several actions on and in the skin interfering with skin biology. Unwanted side effects include hyper-hydration and disorganization of lipid bilayers in the stratum corneum, a dysfunctional barrier, increased susceptibility to irritants and allergies, and increases of skin surface pH. Where the skin barrier is impaired appropriate interventions, e.g. apply lipophilic products in sufficient quantity to treat dry skin or protect the skin from exposure to irritants should be provided. A key statement of this contribution is: every skin care activity matters. Every time something is placed on the skin, a functional and structural response is provoked. This response can be either desired or undesired, beneficial or harmful. The choice of all skin care interventions in nursing and healthcare practice must be based on an accurate assessment

[Grade IIb alkali burns of the lower extremities. Working with concrete].

PubMed

Hasenecker, J M H; Ruchholtz, S; Eming, R; Frangen, T M

2014-01-01

The irritating effects of concrete (calcium oxide) on skin have long been known. The effect by long-term skin exposure is not only irritating but also erosive and alkali skin erosion may result due to colliquative skin necrosis. A complicated course may ensue potentially necessitating plastic reconstructive treatment due to the development of unstable scars and defects. Correct interpretation of the skin trauma and adequate treatment are mandatory for functional restitution.

Resident Rounds: Part III - Case Report: Betel Quid Induced Irritant Contact Dermatitis of the Hand.

PubMed

Mathieu, Regine J; Cheraghi, Nikoo; Russo, Marian A

2016-06-01

Betel quid is a drug used in Far East Asia, India, and the South Pacific. The habit of betel quid chewing is widely reported to cause oral cancer and tooth and gum disease. However, skin disease due to betel quid use is underreported. We report a case of irritant contact dermatitis to betel quid components in a 35-year-old male betel quid user who presented for evaluation of a persistent rash on his fingertips.

Irritability in ADHD: Associations with depression liability.

PubMed

Eyre, Olga; Langley, Kate; Stringaris, Argyris; Leibenluft, Ellen; Collishaw, Stephan; Thapar, Anita

2017-06-01

Irritability and the new DSM-5 diagnostic category of Disruptive Mood Dysregulation Disorder (DMDD) have been conceptualised as related to mood disorder. Irritability is common in Attention Deficit Hyperactivity Disorder (ADHD) but little is known about its association with depression risk in this group. This study aims to establish levels of irritability and prevalence of DMDD in a clinical sample of children with ADHD, and examine their association with anxiety, depression and family history of depression. The sample consisted of 696 children (mean age 10.9 years) with a diagnosis of ADHD, recruited from UK child psychiatry and paediatric clinics. Parents completed the Child and Adolescent Psychiatric Assessment, a semi-structured diagnostic interview, about their child. This was used to establish prevalence of DMDD, anxiety disorder and depressive disorder, as well as obtain symptom scores for irritability, anxiety and depression. Questionnaires assessed current parental depression, and family history of depression. Irritability was common, with 91% endorsing at least one irritable symptom. 3-month DMDD prevalence was 31%. Children with higher levels of irritability or DMDD were more likely to have comorbid symptoms of anxiety, depression and a family history of depression. Results are based on a clinical sample, so may not be generalizable to children with ADHD in the general population. Irritability and DMDD were common, and were associated with markers of depression liability. Longitudinal studies are needed to examine the association between irritability and depression in youth with ADHD as they get older. Copyright © 2017. Published by Elsevier B.V.

Adverse reactions to cosmetics and methods of testing.

PubMed

Nigam, P K

2009-01-01

Untoward reactions to cosmetics, toiletries, and topical applications are the commonest single reason for hospital referrals with allergic contact dermatitis. In most cases, these are only mild or transient and most reactions being irritant rather than allergic in nature. Various adverse effects may occur in the form of acute toxicity, percutaneous absorption, skin irritation, eye irritation, skin sensitization and photosensitization, subchronic toxicity, mutagenicity/genotoxicity, and phototoxicity/photoirritation. The safety assessment of a cosmetic product clearly depends upon how it is used, since it determines the amount of substance which may be ingested, inhaled, or absorbed through the skin or mucous membranes. Concentration of ingredients used in the different products is also important. Various test procedures include in vivo animal models and in vitro models, such as open or closed patch test, in vivo skin irritation test, skin corrosivity potential tests (rat skin transcutaneous electrical resistance test, Episkin test), eye irritation tests (in vivo eye irritancy test and Draize eye irritancy test), mutagenicity/genotoxicity tests (in vitro bacterial reverse mutation test and in vitro mammalian cell chromosome aberration test), and phototoxicity/photoirritation test (3T3 neutral red uptake phototoxicity test). Finished cosmetic products are usually tested in small populations to confirm the skin and mucous membrane compatibility, and to assess their cosmetic acceptability.

Skin hydration and cooling effect produced by the Voltaren® vehicle gel.

PubMed

Hug, Agnes M; Schmidts, Thomas; Kuhlmann, Jens; Segger, Dörte; Fotopoulos, Grigorios; Heinzerling, Johanna

2012-05-01

Voltaren vehicle gel is the carrier substance of the topical Voltaren products. This vehicle gel is especially formulated to be easily applied on the skin, while providing some sensory benefits. The present study aims to substantiate the widely perceived hydrating and cooling effect of Voltaren vehicle gel. Volar forearm skin hydration and transepidermal water loss (TEWL) were measured and user satisfaction was evaluated by questionnaires, after application in 31 healthy, female volunteers. The cooling effect was investigated for 40 min with thermal imaging on 12 forearm sites of six healthy subjects. Voltaren vehicle gel application increased skin hydration by 13.1% (P = 0.0002) when compared with the untreated site, 8 h after the final treatment after 2 weeks. TEWL decreased on both treated (0.37 g/m(2) /h) and untreated (0.74 g/m(2) /h) forearm sites after 2 weeks (8 h after last treatment), demonstrating a relative increase of 6.5% in water loss. Voltaren vehicle gel application resulted in a rapid reduction of skin surface temperature by 5.1°C after only 3 min with an average maximum reduction of 5.8°C after 10 min. The cooling effect was experienced by 94% subjects, while 74% felt that their skin became softer. No adverse events, including skin irritation, were reported during the study and by the 37 participants. This study showed a statistically significant increase in skin hydration as well as a rapid cooling effect lasting approximately 30 min, after application of Voltaren vehicle gel. The small relative increase in water loss may be attributed to an additional skin surface water loss secondary to the increased water content brought into the skin by the Voltaren vehicle gel. The use did not induce any skin irritation and was found acceptable to use by the majority of participants. © 2011 John Wiley & Sons A/S.

Autologous Skin Cell Spray for Massive Soft Tissue War Injuries: A Prospective, Case-Control, Multicenter Trial

DTIC Science & Technology

2014-04-01

randomization design, after all patients are treated with dermal matrix, patients will be randomized to Arm 1 (control group; standard skin grafting with... grafts are often “meshed” or flattened and spread out to increase the size of the skin graft to better cover a large wound. Standard “meshing” increases...the size of the donor graft by 1.5 times (1:1.5). Problems with healing and skin irritation remain with such skin grafts when the injured areas are

Irritable bowel syndrome: contemporary nutrition management strategies.

PubMed

Mullin, Gerard E; Shepherd, Sue J; Chander Roland, Bani; Ireton-Jones, Carol; Matarese, Laura E

2014-09-01

Irritable bowel syndrome is a complex disorder whose pathophysiology involves alterations in the enteric microbiota, visceral hypersensitivity, gut immune/barrier function, hypothalamic-pituitary-adrenal axis regulation, neurotransmitters, stress response, psychological factors, and more. The importance of diet in the management of irritable bowel syndrome has taken center stage in recent times as the literature validates the relationship of certain foods with the provocation of symptoms. Likewise, a number of elimination dietary programs have been successful in alleviating irritable bowel syndrome symptoms. Knowledge of the dietary management strategies for irritable bowel syndrome will help guide nutritionists and healthcare practitioners to deliver optimal outcomes. This tutorial reviews the nutrition management strategies for irritable bowel syndrome. © 2014 American Society for Parenteral and Enteral Nutrition.

Irritant-induced asthma.

PubMed

Labrecque, Manon

2012-04-01

To describe the recent insights into the definition, causes, natural outcome, and key elements of irritant-induced asthma (IIA) management. IIA is a subtype of occupational asthma without immunologic sensitization and includes the typical reactive airway dysfunction syndrome (RADS) and a more gradual form called not-so-sudden IIA, when onset of asthma follows repeated low-dose exposure to irritants. The World Trade Center tragedy brought new insight in the understanding of IIA, suggesting that it can exhibit a prolonged interval between exposure and recognition of clinical symptoms and disease. Dimethyl sulfate has been recently reported to cause RADS and repeated diesel exhaust exposure to cause not-so-sudden IIA in patients who worked in a bus garage. Cleaning workers who are exposed to a large variety of irritants and sensitizers are especially at risk of occupational asthma and IIA. IIA includes RADS and not-so-sudden IIA. Outcome of IIA is as poor as occupational asthma with sensitization. Treatment of IIA does not differ from standard asthma treatment, but high-dose vitamin D could be assessed further for possible therapeutic benefit.

Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design.

PubMed

Isailović, Tanja; Ðorđević, Sanela; Marković, Bojan; Ranđelović, Danijela; Cekić, Nebojša; Lukić, Milica; Pantelić, Ivana; Daniels, Rolf; Savić, Snežana

2016-01-01

We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles - high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50°C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant - polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances.

Relational dimension of irritability following traumatic brain injury: a qualitative analysis.

PubMed

Hammond, Flora M; Davis, Christine S; Cook, James R; Philbrick, Peggy; Hirsch, Mark A

2012-01-01

Irritability is a common long-term sequelae of traumatic brain injury (TBI). In a prior study on TBI irritability, relational interactions were one of four dimensions of irritability occurrence and precipitation. This present analysis examines these same data in greater detail. Fifty focus group transcripts from a study on irritability were re-analysed to examine: (1) irritability in spousal relationships following TBI, (2) retrospective accounts of spousal interactions contributing to irritability and (3) impact of irritability on marital relationships. Grounded Theory was used to develop themes, metacodes and theories. Several theories emerged regarding irritability with respect to spousal relations, all based on the overarching theory that irritability in people with TBI has a strong relational component involved in triggering, experiencing and preventing irritability. Sub-theories supporting this include: (1) irritability breeds further irritability, (2) spousal responses can trigger irritability among persons with TBI and vice versa, (3) difficulties making emotional connections may incite negative interactions, (4) expectations of others may contribute to irritable behaviour, and (5) communication breakdowns may provoke irritability. Irritability associated with TBI resides in the family system as well as the individual. In treating irritability one should include comprehensive assessment and assistance to improve interpersonal interactions.

Non-Animal Testing Approach to EPA Labeling for Eye Irritation

EPA Pesticide Factsheets

This document is an update to EPA’s 2013 published alternative testing approach (using in vitro/ex vivo assays) for determination of eye irritation potential in the pesticide program under EPA's classification and labeling system.

The Behind-the-Knee test: an efficient model for evaluating mechanical and chemical irritation.

PubMed

Farage, Miranda A

2006-05-01

The 'Behind-the-Knee' method (BTK test), using the popliteal fossa as a test site, evaluates both the inherent chemical irritation, and the potential for mechanical irritation of substrates and products. This approach eliminates some of the difficulties of in-use clinical test systems while still providing reliable results. In this publication, examples of the results of BTK tests on several materials are presented with direct comparisons, where possible, with results of in-use clinical testing conducted on the same materials. In in-use clinical tests, volunteer panelists were provided with catamenial products to use in place of their normal product. In the BTK test, samples were applied daily to the popliteal fossa using an elastic athletic band. In both studies, irritation reactions were scored visually. Levels of irritation in the BTK test are consistently higher than those of standard patch tests, illustrating the contribution of mechanical irritation to the overall irritant potential of materials and products. Repeated tests on identical test materials demonstrated that the BTK test results are reproducible. Side-by-side comparisons of the BTK test and in-use clinical tests demonstrated that the BTK test produces results of similar quality to the in-use clinical. By using several concurrent panels with a common test material, it is possible to compare the irritant properties of several materials at once. We have tested over 25 different materials in over 35 BTK studies. The test method has proven reliable and versatile in testing a wide variety of materials, including menstrual pads, topsheets, interlabial pads, pantiliners, tampons and lotion coatings on products. Unlike in-use clinicals, the BTK test allows the direct comparison of two products at one time on the same individual, and is easily adapted to investigative programs. It is subject to fewer confounding factors, is much easier to implement, has a shorter turnaround time, and is less expensive than

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies

PubMed Central

Wang, Zheng; Mu, Hong-Jie; Zhang, Xue-Mei; Ma, Peng-Kai; Lian, Sheng-Nan; Zhang, Feng-Pu; Chu, Sheng-Ying; Zhang, Wen-Wen; Wang, Ai-Ping; Wang, Wen-Yan; Sun, Kao-Xiang

2015-01-01

Background Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). Purpose The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. Methods Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. Results The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil®, 13.44% Cremophor® RH40, 6.72% Labrasol®, and 5.04% Transcutol® HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro®). The microemulsion gel irritated the skin less than Neupro. Conclusion A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability. PMID:25609965

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

PubMed

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

2016-08-01

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

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

PubMed

Ramadan, Qasem; Ting, Fiona Chia Wan

2016-05-21

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

Interventions for photodamaged skin.

PubMed

Samuel, M; Brooke, R C C; Hollis, S; Griffiths, C E M

2005-01-25

Photodamage describes skin changes such as fine and coarse wrinkles, roughness, freckles and pigmentation changes that occur as a result of prolonged exposure to the sun. Many treatments are available to reverse the damage, but it is unclear which work and at what cost in terms of unwanted side effects. To assess the effects of topically applied treatments, tablet treatments, laser and surgical procedures for photodamaged skin. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Issue 1 2002, MEDLINE (1966-June 2002), EMBASE (1974-June 2002), Health Periodicals (1976-June 2002). We checked references of articles and communicated with authors and the pharmaceutical industry. Randomised controlled trials which compared drug or surgical interventions with no treatment, placebo or another drug, in adults with mild, moderate or severe photodamage of the face or forearms. Two reviewers independently extracted data and assessed trial quality. Thirty studies of variable quality were included. Eight trials showed that topical tretinoin cream, in concentrations of 0.02% or higher, was superior to placebo for participants with mild to severe photodamage on the face and forearms (although losses to follow-up were relatively high in most studies). For example, the relative risk of improvement for 0.05% tretinoin cream, compared to placebo (three studies), at 24 weeks, was 1.73 (95% confidence interval 1.39 to 2.14). This effect was not seen for 0.001% topical tretinoin (one study) or 0.01% (three studies). A dose-response relationship was evident for both effectiveness and skin irritation. One small within-patient study showed benefit from topical ascorbic acid compared with placebo. Tazarotene (0.01% to 0.1%) and isotretinoin (0.1%) both showed significant improvement over placebo for moderate photodamage (one study each). There is limited evidence (one trial), to show that the effectiveness of 0.05% tretinoin, is equivalent to the

Co-drug strategy for promoting skin targeting and minimizing the transdermal diffusion of hydroquinone and tranexamic acid.

PubMed

Hsieh, Pei-Wen; Chen, Wei-Yu; Aljuffali, Ibrahim A; Chen, Chun-Che; Fang, Jia-You

2013-01-01

Hydroquinone and tranexamic acids (TXA) are skin-lightening agents with a hydrophilic nature and low skin absorption. A high dose is needed for clinical use, resulting in a high incidence of skin irritation. Co-drugs formed by conjugating hydroquinone and TXA were synthesized and their in vitro and in vivo skin absorption characteristics were evaluated. The two synthesized co-drugs were 4-hydroxyphenyl 4-(aminomethyl)cyclohexanecarboxylate (HAC) and 1,4- phenylene bis(aminomethyl)cyclohexanecarboxylate (BAC). The co-drugs were chemically stable in aqueous solution, but rapidly degraded to the respective parent drug in esterases and skin homogenates. Compared to hydroquinone application, 7.2- and 2.4-fold increments in the hydroquinone skin deposition were obtained with the in vitro application of HAC and BAC. HAC and BAC led to 3- and 2-fold enhancements of equivalent TXA deposition compared to TXA administration. The in vivo experiment showed a further enhancement of co-drugs compared to the in vitro setup. The transdermal penetration of co-drugs, especially BAC, was much lower than that of hydroquinone and TXA. This indicated high-level skin targeting by the co-drugs. HAC and BAC revealed strong affinities for the viable epidermis/dermis. Hair follicles are important reservoirs for co-drug delivery. Daily administration of co-drugs to the skin did not generate irritation for up to 7 days. Both co-drugs are superior candidates for treating skin hyperpigmentation.

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

PubMed

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

2010-04-01

In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt-binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime. Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent. Three cleansing preparations - (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder - were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography. After a 3-week treatment, a significant global treatment effect (P < 0.0001) was found in the atopic group concerning TEWL as indicator for barrier function. A significantly higher TEWL and increasing erythema in the area treated with detergent containing walnut shell powder reflected its irritant effect compared with castor wax beads dispensed in the identical detergent. Cleaning properties of the two formulas were comparably superior to detergent alone. Castor wax beads constitute a novel nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination appropriate for individuals with an atopic skin diathesis in a three-step programme of occupational skin protection. As the skin barrier may additionally be influenced by the composition of dirt and use of skin protection and skin care measures under real workplace

Effectiveness of interventions for preventing occupational irritant hand dermatitis: a quantitative systematic review.

PubMed

Papadatou, Zoi; Williams, Hector; Cooper, Kay

2018-06-01

The aim of this review was to identify, appraise and synthesize the best available evidence on the effectiveness of moisturizers, barrier creams, protective gloves, skin protection education and complex interventions (a combination of two or more of the interventions listed here) in preventing occupational irritant hand dermatitis (OIHD) in wet workers, comparing each intervention to an alternative intervention or to usual care (workers' regular skin care regimen). The most significant occupational skin problem potentially encountered in wet work occupations is occupational dermatitis. When the skin comes into contact with hazardous substances at work, this can cause occupational dermatitis. Substances which may cause occupational dermatitis include cleaning products, organic solvents, metalworking fluids, cement, flour, adhesives, other chemicals and even certain plants. Occupational skin disease has adverse effects on quality of life and the long term prognosis for skin health is poor unless workplace exposures are addressed. To date, no systematic review has been undertaken to determine the effectiveness of interventions for the primary prevention of OIHD in wet workers. The review included any workers from healthcare (e.g. nurses, doctors and allied health professionals) and also people in different wet work occupations (e.g. hairdressers, florists, catering workers, metal workers) at similar risk of OIHD. Studies that assessed the following interventions in the primary prevention of OIHD in wet workers at the workplace and at home (before and after work) were included:Types of studies considered were experimental study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, and before and after studies. Primary outcome measures were OIHD incidence, and secondary outcome measures were product evaluation and change of occupation because of OIHD versus staying in the occupation. Published and unpublished literature in

Combination of 4-hydroxyanisole and all-trans retinoic acid produces synergistic skin depigmentation in swine.

PubMed

Nair, X; Parab, P; Suhr, L; Tramposch, K M

1993-08-01

A combination of 4-hydroxyanisole (4HA) and all-trans retinoic acid (TRA) was found to synergistically cause moderate to complete depigmentation of Yucatan swine skin. Two hyperpigmentation models were used: Natural dark-skinned swine, a potential model for melasma-like disorders, and ultraviolet light-stimulated hyperpigmentation, a model of solar lentigines. Test materials were applied twice daily, 5 d/week, to dorsal flank skin. Application sites were graded at weekly intervals for skin color using a 0 to 4 grading scale. After 8 weeks of treatment of naturally dark swine skin, a combination of 2% 4HA and 0.01% TRA produced grade 2 hypopigmentation (definite but moderate hypopigmentation). In contrast, 2% 4HA alone or 0.01% TRA alone did not produce significant hypopigmentation. After cessation of treatment, the 4HA/TRA-treated sites reverted to normal color within 7-12 weeks. The 4HA/TRA combination completely reversed the hyperpigmentation induced by ultraviolet light after 8 weeks of treatment. In vitro skin-penetration studies using hairless mouse and human skin show that skin penetration of 4HA was not significantly affected by adding 0.01% TRA. These data suggest that the observed synergy is not due to enhanced bioavailability of 4HA. We have demonstrated that combining low concentrations of 4HA and TRA results in effective skin lightening without causing irreversible depigmentation and with minimal local skin irritation.

Evaluation of Beryllium, Total Chromium and Nickel in the Surface Contaminant Layer Available for Dermal Exposure After Abrasive Blasting in a Shipyard

DTIC Science & Technology

2013-04-24

established to minimize the potential of dermal irritation and dermatitis (6). Chromium exposure can lead to allergic contact dermatitis , irritant... dermatitis with skin contact . (5; 15; 25; 33; 47). Nickel is potentially the most common contact allergen among the general population. Some studies...thresholds - a review focusing on occluded nickel exposure. Contact Dermatitis 52:57-64 21. Fogh CL, Andersson KG. 2000. Modelling of skin exposure

The hen's egg chorioallantoic membrane (HET-CAM) test to predict the ophthalmic irritation potential of a cysteamine-containing gel: Quantification using Photoshop® and ImageJ.

PubMed

McKenzie, Barbara; Kay, Graeme; Matthews, Kerr H; Knott, Rachel M; Cairns, Donald

2015-07-25

A modified hen's egg chorioallantoic membrane (HET-CAM) test has been developed, combining ImageJ analysis with Adobe(®) Photoshop(®). The irritation potential of an ophthalmic medicine can be quantified using this method, by monitoring damage to blood vessels. The evaluation of cysteamine containing hyaluronate gel is reported. The results demonstrated that the novel gel formulation is non-irritant to the ocular tissues, in line with saline solution (negative control). In conclusion, the modification of the established HET-CAM test can quantify the damage to minute blood vessels. These results offer the possibility to formulate cysteamine in an ocular applicable gel formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Occupational skin diseases in dental laboratory technicians. (I). Clinical picture and causative factors.

PubMed

Rustemeyer, T; Frosch, P J

1996-02-01

In Germany, occupational skin disease (OSD) in dental technicians (DT) has been steadily rising in recent years and causing considerable costs for medical care and rehabilitation. Our objective in this study was to: (i) examine affected workers; (ii) perform patch tests to identify causative agents; (iii) develop strategies of prevention. 7 dental laboratories were inspected as to materials used, working habits, safety regulations, etc. A computer data base was developed for products (trade name, active ingredient, additives, etc.). A questionnaire regarding development of OSD was sent out to 1132 dental technicians (45 questions). 55 DT with suspected OSD were examined and patch tested with the standard series, an extensive series of methacrylates, and own materials. Working conditions, and knowledge of potential hazards, varied greatly in the laboratories visited. The safety data sheets of working materials were of little use and required supplementation by the computer data base, which provided rapid access to allergological information (e.g., type of acrylate, concentration). In the questionnaire (173 answers), 36% reported skin lesions attributed to work and 1/3 suspected plastic materials as their primary cause. Among the 55 DT examined, allergic contact dermatitis was diagnosed in 63.6% and irritant contact dermatitis in 23.6%. Most of the allergens identified (74%) were found in plastic materials (methyl methacrylate (MMA), 9 patients (16%); 2-hydroxyethyl methacrylate (2-HEMA), 18 patients (33%); ethyleneglycol dimethacrylate (EGDMA), 15 patients (27%)). In 16 patients, multiple sensitizations to various methacrylates were found. The fingertips were primarily involved in allergic contact dermatitis (93%), whereas in irritant contact dermatitis, the dorsa of the fingers (especially of the dominant hand) were affected (80%). 9 patients also showed lesions on the face, neck and forearms. The main irritant factors included wet work, contact with plaster

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.

The Sub-Regional Functional Organization of Neocortical Irritative Epileptic Networks in Pediatric Epilepsy

PubMed Central

Janca, Radek; Krsek, Pavel; Jezdik, Petr; Cmejla, Roman; Tomasek, Martin; Komarek, Vladimir; Marusic, Petr; Jiruska, Premysl

2018-01-01

Between seizures, irritative network generates frequent brief synchronous activity, which manifests on the EEG as interictal epileptiform discharges (IEDs). Recent insights into the mechanism of IEDs at the microscopic level have demonstrated a high variance in the recruitment of neuronal populations generating IEDs and a high variability in the trajectories through which IEDs propagate across the brain. These phenomena represent one of the major constraints for precise characterization of network organization and for the utilization of IEDs during presurgical evaluations. We have developed a new approach to dissect human neocortical irritative networks and quantify their properties. We have demonstrated that irritative network has modular nature and it is composed of multiple independent sub-regions, each with specific IED propagation trajectories and differing in the extent of IED activity generated. The global activity of the irritative network is determined by long-term and circadian fluctuations in sub-region spatiotemporal properties. Also, the most active sub-region co-localizes with the seizure onset zone in 12/14 cases. This study demonstrates that principles of recruitment variability and propagation are conserved at the macroscopic level and that they determine irritative network properties in humans. Functional stratification of the irritative network increases the diagnostic yield of intracranial investigations with the potential to improve the outcomes of surgical treatment of neocortical epilepsy. PMID:29628910

Ex vivo permeation of carprofen from nanoparticles: A comprehensive study through human, porcine and bovine skin as anti-inflammatory agent.

PubMed

Parra, Alexander; Clares, Beatriz; Rosselló, Ana; Garduño-Ramírez, María L; Abrego, Guadalupe; García, María L; Calpena, Ana C

2016-03-30

The purpose of this study was the development of poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) for the dermal delivery of carprofen (CP). The developed nanovehicle was then lyophilized using hydroxypropyl-β-cyclodextrin (HPβCD) as cryoprotectant. The ex vivo permeation profiles were evaluated using Franz diffusion cells using three different types of skin membranes: human, porcine and bovine. Furthermore, biomechanical properties of skin (trans-epidermal water loss and skin hydration) were tested. Finally, the in vivo skin irritation and the anti-inflammatory efficacy were also assayed. Results demonstrated the achievement of NPs 187.32 nm sized with homogeneous distribution, negatively charged surface (-23.39 mV) and high CP entrapment efficiency (75.38%). Permeation studies showed similar diffusion values between human and porcine skins and higher for bovine. No signs of skin irritation were observed in rabbits. Topically applied NPs significantly decreased in vivo inflammation compared to the reference drug in a TPA-induced mouse ear edema model. Thus, it was concluded that NPs containing CP may be a useful tool for the dermal treatment of local inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuously varying skin potentials elicited by sinusoidally varying electric shock potentials

NASA Technical Reports Server (NTRS)

Senders, J. W.; Senders, V. L.; Tursky, B.

1973-01-01

An investigation was carried out to determine whether a form of quasi-linear systems analysis can be applied to electrodormal responses to yield new insights into the nature of the response mechanisms and their interrelationships. The response investigated was the electrodermal response (galvanic skin potential, GSP) as elicited by an electric shock stimulus applied to the skin. The response subsequent to this stimulation was examined and its characteristics measured. A series of experimental runs on three Ss was accomplished, using sinusoidal modulation envelopes of frequencies. Results showed that it was possible to drive the GSP and to achieve relatively high coherence between the driving frequency and the response itself. The analysis was limited to Fourier analysis of the response in order to determine the relative energies at the driving frequency and at successive harmonics of that driving frequency, and correlational analysis in order to determine the degree of linear relationship between the driving frequency and the driven response.

Use of the Bovine Udder Skin model to evaluate the tolerability of Mesem cosmetic cream.

PubMed

Raak, Christa; Molsberger, Friedrich; Pittermann, Wolfgang; Bertram, Mathias; Robens, Sibylle; Ostermann, Thomas

2017-09-01

Observational studies of Mesem cream (based on Mesembryanthemum crystallinum L. plant extract) found that it had positive effects on skin hydration and smoothing of the skin. However, some patients reported skin irritation effects. The current study evaluated the skin tolerability of Mesem cream, as compared to the carrier cream (without the active ingredient), by using the isolated perfused bovine udder skin model. The primary outcomes investigated were cytotoxicity (i.e. cell viability), assessed with the MTT assay, and irritancy and inflammation, assessed by measuring PGE₂ tissue levels. A total reaction score was calculated by combining the results for each parameter. In the case of a single topical application, significant differences were found between the carrier cream and the Mesem cream. While the application of carrier cream resulted in low cytotoxicity (-8.4% change in viability, as compared to the untreated control), the Mesem cream was more cytotoxic (-18.7% change). In addition, one hour after application, PGE₂ levels were higher in Mesem cream-treated skin, as compared to carrier cream-treated skin (16.6% versus 11.3%). Further experiments (tape-stripped skin and repeated application) also found significant differences between the two creams in the results obtained. Evaluation of the effectiveness, safety and tolerability of phyto-cosmetic products is important. Our results confirmed the findings of two previous human observational studies (the human patch test and open application study). Future experiments to understand the underlying principles of its effectiveness, safety and tolerability should include extracts of M. crystallinum L. juice, as well as the Mesem cream itself. 2017 FRAME.

Developmental Trajectories of Irritability and Bidirectional Associations With Maternal Depression

PubMed Central

Wiggins, Jillian Lee; Mitchell, Colter; Stringaris, Argyris; Leibenluft, Ellen

2014-01-01

Objective Irritability is a dimensional trait in typical development and a common presenting symptom in many psychiatric disorders, including depression. However, little is known about the developmental trajectory of irritability or how child irritability interacts with maternal depression. The present study (1) identifies classes of irritability trajectories from toddlerhood to middle childhood; (2) characterizes maternal depression and other family, social environment, and child variables within each irritability trajectory class; and (3) as a more exploratory analysis, examines bidirectional associations between maternal depression and child irritability. Method 4,898 families from the Fragile Families and Child Wellbeing Study reported on irritability symptoms at ages 3, 5, and 9, assessed with items from the Child Behavior Checklist. Parental major depressive episode was assessed using the Composite International Diagnostic Interview – Short Form at child ages 1, 3, 5, 9. Results A latent class growth analysis identified five irritability classes: low decreasing; moderate decreasing; high steady; initially very high, then decreasing; and high increasing. Children with more severe irritability trajectories are more likely to have mothers with recurrent depression, and, with the exception of the most severe (high increasing irritability) class, were more likely to have mothers who were exposed to violence. Moreover, paternal depression and alcohol use, as well as maternal drug and alcohol use, were also risk factors for membership in the more severe irritability classes. A latent auto-regressive cross-lag model showed that child irritability at ages 3 and 5 is associated with increased mother depression at 5 and 9, respectively. Conversely, mother depression at child ages 1 and 3 is associated with increased child irritability at 3 and 5. Conclusion Irritability development across toddlerhood and middle childhood has five main trajectory types, which differ on

Developmental trajectories of irritability and bidirectional associations with maternal depression.

PubMed

Wiggins, Jillian Lee; Mitchell, Colter; Stringaris, Argyris; Leibenluft, Ellen

2014-11-01

Irritability is a dimensional trait in typical development and a common presenting symptom in many psychiatric disorders, including depression. However, little is known about the developmental trajectory of irritability or how child irritability interacts with maternal depression. The present study identifies classes of irritability trajectories from toddlerhood to middle childhood; characterizes maternal depression and other family, social environment, and child variables within each irritability trajectory class; and, as a more exploratory analysis, examines bidirectional associations between maternal depression and child irritability. A total of 4,898 families from the Fragile Families and Child Wellbeing Study reported on irritability symptoms at ages 3, 5, and 9 years, assessed with items from the Child Behavior Checklist. Parental major depressive episode was assessed using the Composite International Diagnostic Interview-Short Form at child ages 1, 3, 5, and 9 years. A latent class growth analysis identified 5 irritability classes: low decreasing; moderate decreasing; high steady; initially very high, then decreasing; and high increasing. Children with more severe irritability trajectories are more likely to have mothers with recurrent depression, and, with the exception of the most severe (high increasing irritability) class, were more likely to have mothers who were exposed to violence. Moreover, paternal depression and alcohol abuse, as well as maternal drug and alcohol abuse, were also risk factors for membership in the more severe irritability classes. A latent auto-regressive cross-lag model showed that child irritability at ages 3 and 5 years is associated with increased mother depression at ages 5 and 9, respectively. Conversely, mother depression at child ages 1 and 3 years is associated with increased child irritability at 3 and 5. Irritability development across toddlerhood and middle childhood has 5 main trajectory types, which differ on maternal

Skin reactions related to hand hygiene and selection of hand hygiene products.

PubMed

Larson, Elaine; Girard, Raphaelle; Pessoa-Silva, Carmem Lucia; Boyce, John; Donaldson, Liam; Pittet, Didier

2006-12-01

In October 2004, The World Health Organization (WHO) launched the World Alliance for Patient Safety. Within the alliance, the first priority of the Global Patient Safety Challenge is to reduce health care-associated infection. A key action within the challenge is to promote hand hygiene in health care globally as well as at the country level through the campaign "Clean Care is Safer Care." As a result, the WHO is developing Guidelines on Hand Hygiene in Health Care, designed to be applicable throughout the world. This paper summarizes one component of the global WHO guidelines related to the impact of hand hygiene on the skin of health care personnel, including a discussion of types of skin reactions associated with hand hygiene, methods to reduce adverse reactions, and factors to consider when selecting hand hygiene products. Health care professionals have a higher prevalence of skin irritation than seen in the general population because of the necessity for frequent hand hygiene during patient care. Ways to minimize adverse effects of hand hygiene include selecting less irritating products, using skin moisturizers, and modifying certain hand hygiene practices such as unnecessary washing. Institutions need to consider several factors when selecting hand hygiene products: dermal tolerance and aesthetic preferences of users as well as practical considerations such as convenience, storage, and costs.

Potential of EPR spin-trapping to investigate in situ free radicals generation from skin allergens in reconstructed human epidermis: cumene hydroperoxide as proof of concept.

PubMed

Kuresepi, Salen; Vileno, Bertrand; Turek, Philippe; Lepoittevin, Jean-Pierre; Giménez-Arnau, Elena

2018-02-01

The first step in the development of skin sensitisation to a chemical, and in the elicitation of further allergic contact dermatitis (ACD), is the binding of the allergen to skin proteins after penetrating into the epidermis. The so-formed antigenic adduct is then recognised by the immune system as foreign to the body. Sensitising organic hydroperoxides derived from autoxidation of natural terpenes are believed to form antigens through radical-mediated mechanisms, although this has not yet been established. So far, in vitro investigations on reactive radical intermediates derived from these skin sensitisers have been conducted in solution, yet with experimental conditions being far away from real-life sensitisation. Herein, we report for the first time, the potential use of EPR spin-trapping to study the in situ generation of free radicals derived from cumene hydroperoxide CumOOH in a 3D reconstructed human epidermis (RHE) model, thus much closer to what may happen in vivo. Among the undesirable effects associated with dermal exposure to CumOOH, it is described to cause allergic and irritant dermatitis, being reported as a significant sensitiser. We considered exploiting the usage of spin-trap DEPMPO as an extensive view of all sort of radicals derived from CumOOH were observed all at once in solution. We showed that in the Episkin TM RHE model, both by incubating in the assay medium and by topical application, carbon radicals are mainly formed by redox reactions suggesting the key role of CumOOH-derived carbon radicals in the antigen formation process.

Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea.

PubMed

Pimentel, M

2016-01-01

The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin). To review the literature regarding the role of rifaximin in IBS and its potential mechanism(s) of action. A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'. Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO. Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS. © 2015 John Wiley & Sons Ltd.

Antioxidant activity and irritation property of venoms from Apis species.

PubMed

Somwongin, Suvimol; Chantawannakul, Panuwan; Chaiyana, Wantida

2018-04-01

as cosmetic ingredients since it possessed the highest antioxidant activity with no irritation. This study is the first report to compare the bee venom extracts from different Apis species and display their potential application of bee venom extracts in cosmetic products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment.

PubMed

Friis, Ulrik F; Menné, Torkil; Schwensen, Jakob F; Flyvholm, Mari-Ann; Bonde, Jens P E; Johansen, Jeanne D

2014-12-01

Irritant contact dermatitis (ICD) is a common diagnosis in patients with occupational contact dermatitis (OCD). Studies are lacking on the usefulness of material safety data sheets (MSDSs) in making the diagnosis of ICD. To characterize irritant exposures leading to the diagnosis of occupational ICD (OICD), and to evaluate the occurrence of concomitant exposures to contact allergens. We included 316 patients with suspected occupational hand dermatitis, referred to the Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark during January 2010-August 2011, in a programme consisting of a clinical examination, exposure assessment, and extensive patch/prick testing. OCD was diagnosed in 228 patients. Of these patients, 118 were diagnosed with OICD. The main irritant exposures identified were wet work (n = 64), gloves (n = 45), mechanical traumas (n = 19), and oils (n = 15). Exposure to specific irritant chemicals was found in 9 patients, and was identified from MSDSs/ingredients labelling in 8 of these patients. Review of MSDSs and ingredients labelling showed that 41 patients were exposed to 41 moderate to potent contact allergens, and 18 patients were exposed to 25 weak workplace contact allergens. In the present study, the systematic exposure assessment did not reveal any new irritants. MSDSs have a limited role in the investigation of ICD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy of clavulanate-potentiated amoxycillin in experimental and clinical skin infections.

PubMed

Bywater, R J; Hewett, G R; Marshall, A B; West, B

1985-02-16

The efficacy of clavulanate-potentiated amoxycillin was compared with amoxycillin alone in experimental staphylococcal infection in dogs and in a controlled trial in clinical cases of skin infection in dogs and cats. The experimental infection was produced by subdermal inoculation with beta-lactamase producing (amoxycillin resistant) staphylococci absorbed in cotton dust. This produced discrete, localised lesions with no systemic involvement. In a cross over study, six animals were randomly allocated to treatment with either amoxycillin alone (10 mg/kg, dosed twice daily) or a formulation of clavulanate-potentiated amoxycillin (12.5 mg/kg, of a 1:4 ratio, dosed twice daily). The lesions of the animals treated with clavulanate-potentiated amoxycillin resolved more quickly than those treated with amoxycillin alone. The difference was significant (P less than 0.05) for both lesion diameter and inflammation score after day 6 of treatment. A trial was carried out in clinical cases of skin disease which were randomly allocated to twice daily treatment with either amoxycillin alone (10 or 20 mg/kg), or with clavulanate-potentiated amoxycillin (12.5 or 25 mg/kg of a 1:4 ratio). The required duration of treatment was shorter (P less than 0.5) for the potentiated amoxycillin treatments, and the success rate (judged by cure or substantial improvement) was higher (P less than 0.05) for this group, especially (P less than 0.01) where amoxycillin resistant organisms were isolated. It was concluded that clavulanate-potentiated amoxycillin was an effective treatment of skin infections both under experimental and clinical conditions.

Insect antimicrobial peptides: potential tools for the prevention of skin cancer.

PubMed

Tonk, Miray; Vilcinskas, Andreas; Rahnamaeian, Mohammad

2016-09-01

Antimicrobial peptides/proteins (AMPs) are biologically active molecules with diverse structural properties that are produced by mammals, plants, insects, ticks, and microorganisms. They have a range of antibacterial, antifungal, antiviral, and even anticancer activities, and their biological properties could therefore be exploited for therapeutic and prophylactic applications. Cancer and cancer drug resistance are significant current health challenges, so the development of innovative cancer drugs with minimal toxicity toward normal cells and novel modes of action that can evade resistance may provide a new direction for anticancer therapy. The skin is the first line of defense against heat, sunlight, injury, and infection, and skin cancer is thus the most common type of cancer. The skin that has been exposed to sunlight is particularly susceptible, but lesions can occur anywhere on the body. Skin cancer awareness and self-efficacy are necessary to improve sun protection behavior, but more effective preventative approaches are also required. AMPs may offer a new prophylactic approach against skin cancer. In this mini review, we draw attention to the potential use of insect AMPs for the prevention and treatment of skin cancer.

Skin appendage-derived stem cells: cell biology and potential for wound repair.

PubMed

Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

2016-01-01

Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundamental characteristics, their preferentially expressed biomarkers, and their potential contribution involved in wound repair. Finally, we will also discuss current strategies, future applications, and limitations of these stem cells, attempting to provide some perspectives on optimizing the available therapy in cutaneous repair and regeneration.

Predictive performance of the Vitrigel‐eye irritancy test method using 118 chemicals

PubMed Central

Yamaguchi, Hiroyuki; Kojima, Hajime

2015-01-01

Abstract We recently developed a novel Vitrigel‐eye irritancy test (EIT) method. The Vitrigel‐EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time‐dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel‐EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel‐EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false‐negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false‐positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO‐1, a tight junction‐associated protein and MUC1, a cell membrane‐spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false‐positive chemicals, suggesting that such false‐positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel‐EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel‐EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID:26472347

Predictive performance of the Vitrigel-eye irritancy test method using 118 chemicals.

PubMed

Yamaguchi, Hiroyuki; Kojima, Hajime; Takezawa, Toshiaki

2016-08-01

We recently developed a novel Vitrigel-eye irritancy test (EIT) method. The Vitrigel-EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time-dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel-EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel-EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false-negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false-positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO-1, a tight junction-associated protein and MUC1, a cell membrane-spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false-positive chemicals, suggesting that such false-positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel-EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel-EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

[Impact of wet work on epidermal barrier (tewl and stratum corneum hydration) and skin viscoelasticity in nurses].

PubMed

Kieć-Świcrczyńska, Marta; Chomiczewska-Skóra, Dorota; Świerczyńska-Machura, Dominika; Kręcisz, Beata

2014-01-01

Nurses are prone to develop hand eczema due to occupational exposure to irritants, including wet work. The aim of the study was to evaluate the impact of wet work on selected skin properties, reflecting epidermal barrier function--transepidermal water loss (TEWL) and stratum corneum hydration--and additionally skin viscoelasticity, in nurses. Study subjects included 90 nurses employed in hospital wards. Measurements were carried out within the dorsal aspect of the dominant hand, using a Cutometer MPA 580 equipped with Tewameter TM 300 and Corneometer CM 825 (Courage & Khazaka, Germany) probes. Examina- tions took place on hospital premises. Similar measurements were performed in the control group of females non-exposed to irritants. In the examined group of nurses, mean TEWL was 15.5 g/h/m2 and was higher than in the control group (12.99 g/h/m2). After rejecting the extreme results, the difference between the groups proved to be statistically significant (p < 0.05). The mean value of stratum corneum hydration was lower in the examined group (37.915) compared with the control group (40.05), but the difference was not sta tistically significant. Also results of viscoelasticity assessment showed no significant differences between studied groups. The results of the assessment of skin biophysical properties show that wet work exerts a moderately adverse impact on skin condition. A higher TEWL value and a lower stratum corneum hydration in workers exposed to irritants reflect an adverse impact of these factors on the epidermal barrier function.

Specific dermatological benefits associated with quantities of lotion transferred to the skin.

PubMed

Farage, Miranda A; Esquerra, Juan; Cheng, Richard; Carpenter, Stacey; Bunasky, Kathryn; Gutshall, Denise; Lawrence, Ann; Messerschmidt, Andre

2017-11-02

A growing number of manufacturers are taking advantage of the ability of absorbent consumer products to deliver lotion to the skin. The lotion is included on these products to help protect the skin from adverse skin effects that can occur, including: (1) irritation, (2) over hydration of the stratum corneum, (3) dryness that can occur from extended exposure to highly absorbent consumer products, and (4) changes in pH. This manuscript presents results of a quantitative lotion transfer study of adult incontinence products. Resulting lotion transfer is compared to the results of several separate experiments in which specific skin benefits have been correlated to lotion concentrations. The behind-the-knee (BTK) lotion transfer protocol was used to quantitate lotion transfer from adult incontinence (AI) test products constructed using 2 lotion formulations and 2 configurations of lotion application. A modified arm patch protocol, in which skin sites of a measured dimension were pre-treated with specific volumes of lotion, was used to evaluate protective effects of lotion against exposure to irritants, and over hydration from wetted absorbent products. After a 6-hours continuous exposure in the BTK the 5-stripe lotion configuration products transferred (adjusted mean ± SE) 94 ± 11-104 ± 11 μg/cm 2 lotion. After 24 hours of wear, transfer had increased to 127 ± 22 and 149 ± 24 μg/cm 2 , respectively. The single-block configuration products transferred 289 ± 10-316 ± 10 μg/cm 2 (P = .04). Transfer after 24 hours of wear was 328 ± 23 and 472 ± 21 μg/cm 2 , respectively (P < .0001). Several protocols were used to evaluate the concentration of lotion required to provide four specific skin benefits. In studies evaluating protection against irritants, skin site pre-treated with lotion were patched with 0.5% sodium lauryl sulfate (SLS). Protective effects were assessed by visual assessment of erythema and trans-epidermal water loss (TEWL

Management of Central Venous Access Device-Associated Skin Impairment: An Evidence-Based Algorithm.

PubMed

Broadhurst, Daphne; Moureau, Nancy; Ullman, Amanda J

Patients relying on central venous access devices (CVADs) for treatment are frequently complex. Many have multiple comorbid conditions, including renal impairment, nutritional deficiencies, hematologic disorders, or cancer. These conditions can impair the skin surrounding the CVAD insertion site, resulting in an increased likelihood of skin damage when standard CVAD management practices are employed. Supported by the World Congress of Vascular Access (WoCoVA), developed an evidence- and consensus-based algorithm to improve CVAD-associated skin impairment (CASI) identification and diagnosis, guide clinical decision-making, and improve clinician confidence in managing CASI. A scoping review of relevant literature surrounding CASI management was undertaken March 2014, and results were distributed to an international advisory panel. A CASI algorithm was developed by an international advisory panel of clinicians with expertise in wounds, vascular access, pediatrics, geriatric care, home care, intensive care, infection control and acute care, using a 2-phase, modified Delphi technique. The algorithm focuses on identification and treatment of skin injury, exit site infection, noninfectious exudate, and skin irritation/contact dermatitis. It comprised 3 domains: assessment, skin protection, and patient comfort. External validation of the algorithm was achieved by prospective pre- and posttest design, using clinical scenarios and self-reported clinician confidence (Likert scale), and incorporating algorithm feasibility and face validity endpoints. The CASI algorithm was found to significantly increase participants' confidence in the assessment and management of skin injury (P = .002), skin irritation/contact dermatitis (P = .001), and noninfectious exudate (P < .01). A majority of participants reported the algorithm as easy to understand (24/25; 96%), containing all necessary information (24/25; 96%). Twenty-four of 25 (96%) stated that they would recommend the tool to

The menstrual cycle and the skin.

PubMed

Raghunath, R S; Venables, Z C; Millington, G W M

2015-03-01

Perimenstrual exacerbations of dermatoses are commonly recognized, yet our knowledge of the underlying pathophysiological mechanisms remains imperfect. Research into the effects of oestrogen on the skin has provided evidence to suggest that oestrogen is associated with increases in skin thickness and dermal water content, improved barrier function, and enhanced wound healing. Research into the effects of progesterone suggests that the presence of various dermatoses correlates with peak levels of progesterone. Dermatoses that are exacerbated perimenstrually include acne, psoriasis, atopic eczema and irritant dermatitis, and possibly also erythema multiforme. Exacerbations occur at the peak levels of progesterone in the menstrual cycle. Underlying mechanisms include reduced immune and barrier functions as a result of cyclical fluctuations in oestrogen and/or progesterone. Autoimmune progesterone and oestrogen dermatitis are the best-characterized examples of perimenstrual cutaneous reactions to hormones produced during the menstrual cycle. In this review, we describe the current understanding of the menstrual cycle, and its effect on the skin and cutaneous disorders. © 2015 British Association of Dermatologists.

16 CFR 1500.42 - Test for eye irritants.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Test for eye irritants. 1500.42 Section 1500... eye irritants. (a)(1) Six albino rabbits are used for each test substance. Animal facilities for such... materials that might produce eye irritation. Both eyes of each animal in the test group shall be examined...

Role of macromolecules in the safety of use of body wash cosmetics.

PubMed

Bujak, Tomasz; Wasilewski, Tomasz; Nizioł-Łukaszewska, Zofia

2015-11-01

One of the most challenging problems related to the use of surfactants in body wash cosmetics is their potential to cause skin irritations. Surfactants can bind with proteins, remove lipids from the epidermal surface, contribute to the disorganization of liquid crystal structures in the intercellular lipids, and interact with living skin cells. These processes can lead to skin irritations and allergic reactions, and impair the epidermal barrier function. The present study is an attempt to assess the effect of polymers and hydrolysed proteins present in the formulations of model body wash cosmetics on product properties. Special attention was given to the safety of use of this product type. The study examined three macromolecules: polyvinylpyrrolidone (PVP), hydrolysed wheat protein (HWP) and polyvinylpyrrolidone/hydrolysed wheat protein crosspolymer (PVP/HWP). The addition of the substances under study was found to improve the foaming properties of body wash cosmetics, increase their stability during storage, and contribute significantly to an improvement in the safety of product use by reducing the irritant potential. The strongest ability to reduce the skin irritation potential was determined for the formula enriched with the PVP/HWP crosspolymer. Copyright © 2015 Elsevier B.V. All rights reserved.

Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate.

PubMed

Wu, Dan; Katsumi, Hidemasa; Quan, Ying-Shu; Kamiyama, Fumio; Kusamori, Kosuke; Sakane, Toshiyasu; Yamamoto, Akira

2016-09-01

Available formulations of sumatriptan succinate (SS) have low bioavailability or are associated with site reactions. We developed various types of self-dissolving microneedle arrays (MNs) fabricated from sodium hyaluronate as a new delivery system for SS and evaluated their skin permeation and irritation in terms of clinical application. In vitro permeation studies with human skin, physicochemical properties (needle length, thickness and density), and penetration enhancers (glycerin, sodium dodecyl sulfate and lauric acid diethanolamide) were investigated. SS-loaded high-density MNs of 800 µm in length were the optimal formulation and met clinical therapeutic requirements. Penetration enhancers did not significantly affect permeation of SS from MNs. Optical coherence tomography images demonstrated that SS-loaded high-density MNs (800 µm) uniformly created drug permeation pathways for the delivery of SS into the skin. SS-loaded high-density MNs induced moderate primary skin irritations in rats, but the skin recovered within 72 h of removal of the MNs. These findings suggest that high-density MNs of 800 µm in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs.

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.

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

PubMed

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

2017-12-01

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

PSYCHOLOGICAL ASPECTS OF IRRITABLE BOWEL SYNDROME

PubMed Central

Rajagopalan, Mani; Kurian, George; John, Jacob K.

1996-01-01

Psychological aspects of Irritable Bowel Syndrome have been well investigated in Western countries, but there is a paucity of Indian studies focusing on this area. A series of fifty patients with the Irritable Bowel Syndrome were studied with respect to their depressive symptoms, anxiety symptoms and their personality traits. Patients had a mean score of 14.68 on Hamilton's depression rating scale and 11.22 on Hamilton's anxiety rating scale, and were more introverted and more neurotic than the general population. No association was found between psychological symptoms and severity of gastrointestinal symptoms. These findings suggest that psychological symptoms are a concomitant part of the Irritable Bowel Syndrome. PMID:21584134

Cocoa Bioactive Compounds: Significance and Potential for the Maintenance of Skin Health

PubMed Central

Scapagnini, Giovanni; Davinelli, Sergio; Di Renzo, Laura; De Lorenzo, Antonino; Olarte, Hector Hugo; Micali, Giuseppe; Cicero, Arrigo F.; Gonzalez, Salvador

2014-01-01

Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health. PMID:25116848

SU-E-J-273: Skin Temperature Recovery Rate as a Potential Predictor for Radiation-Induced Skin Reactions

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

Biswal, N C; Wu, Z; Chu, J

Purpose: To assess the potential of dynamic infrared imaging to evaluate early skin reactions during radiation therapy in cancer patients. Methods: Thermal images were captured by our home-built system consisting of two flash lamps and an infrared (IR) camera. The surface temperature of the skin was first raised by ∼ 6 °C from ∼1 ms short flashes; the camera then captured a series of IR images for 10 seconds. For each image series, a basal temperature was recorded for 0.5 seconds before flash was triggered. The temperature gradients (ε) were calculated between a reference point (immediately after the flash) andmore » at a time point of 2sec, 4sec and 9sec after that. A 1.0 cm region of interest (ROI) on the skin was drawn; the mean and standard deviations of the ROIs were calculated. The standard ε values for normal human skins were evaluated by imaging 3 healthy subjects with different skin colors. All of them were imaged on 3 separate days for consistency checks. Results: The temperature gradient, which is the temperature recovery rate, depends on the thermal properties of underlying tissue, i.e. thermal conductivity. The average ε for three volunteers averaged over 3 measurements were 0.64±0.1, 0.72±0.2 and 0.80±0.3 at 2sec, 4sec and 9sec respectively. The standard deviations were within 1.5%–3.2%. One of the volunteers had a prior small skin burn on the left wrist and the ε values for the burned site were around 9% (at 4sec) and 13% (at 9sec) lower than that from the nearby normal skin. Conclusion: The temperature gradients from the healthy subjects were reproducible within 1.5%–3.2 % and that from a burned skin showed a significant difference (9%–13%) from the normal skin. We have an IRB approved protocol to image head and neck patients scheduled for radiation therapy.« less

Acute skin lesions after surgical procedures: a clinical approach.

PubMed

Borrego, L

2013-11-01

In the hospital setting, dermatologists are often required to evaluate inflammatory skin lesions arising during surgical procedures performed in other departments. These lesions can be of physical or chemical origin. Povidone iodine is the most common reported cause of such lesions. If this antiseptic solution remains in contact with the skin in liquid form for a long period of time, it can give rise to serious irritant contact dermatitis in dependent or occluded areas. Less common causes of skin lesions after surgery include allergic contact dermatitis and burns under the dispersive electrode of the electrosurgical device. Most skin lesions that arise during surgical procedures are due to an incorrect application of antiseptic solutions. Special care must therefore be taken during the use of these solutions and, in particular, they should be allowed to dry. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Potential Application of Nanoemulsions for Skin Delivery of Pomegranate Peel Polyphenols.

PubMed

Baccarin, Thaisa; Lemos-Senna, Elenara

2017-11-01

Pomegranate peel and seeds have demonstrated to possess antioxidant compounds with potential application to protect the skin against the ultraviolet radiation damage. However, the photoprotection activity is dependent on the amount of these compounds that reach the viable skin layers. In this paper, we describe the in vitro skin permeation and retention of the major pomegranate peel polyphenols using Franz diffusion cells, after entrapping a ethyl acetate fraction (EAF) from Punica granatum peel extract into nanoemulsions (NEs) prepared with pomegranate seed oil (PSO) or medium chain triglyceride oil (MCT). The in vitro skin permeation of gallic acid (GA), ellagic acid (EA), and punicalagin (PC) was evaluated using a HPLC-DAD validated method. After 8 h of skin permeation, all polyphenol compounds were mostly retained in the skin and did not reach the receptor compartment. However, a 2.2-fold enhancement of the retained amount of gallic acid in the stratum corneum was verified after EAF-loaded NEs are applied, when compared with the free EAF. GA and EA were delivered to the viable epidermis and dermis only when nanoemulsions were applied onto the skin. The mean retained amounts of GA and EA in the EP and DE after applying the EAF-loaded PSO-NE were 1.78 and 1.36 μg cm -2 and 1.10 and 0.97 μg cm -2 , respectively. Similar values were obtained after applying the EAF-loaded MCT-NE. The skin permeation results were supported by the confocal microscopy images. These results evidenced the promising application of nanoemulsions to deliver the pomegranate polyphenols into the deeper skin layers.

Mineral intake independent from gastric irritation or pica by cell-dehydrated rats.

PubMed

Constancio, Juliana; Pereira-Derderian, Daniela T B; Menani, José V; De Luca, Laurival A

2011-10-24

Gavage of 2 M NaCl (IG 2 M NaCl), a procedure to induce cell-dehydration-and water and 0.15 M NaCl intake in a two-bottle choice test-is also a potential gastric irritant. In this study, we assessed whether mineral intake induced by IG 2 M NaCl is associated with gastric irritation or production of pica in the rat. We first determined the amount of mineral solution (0.15 M NaCl, 0.15 M NaHCO3, 0.01 M KCl and 0.05 mM CaCl2) and water ingested in response to IG 2 M NaCl in a five-bottle test. Then, we used mineral solutions (0.01 M KCl and 0.15 M NaHCO3), whose intakes were significantly increased compared to controls, and water in three-bottle tests to test the gastric irritation hypothesis. The IG 2 M NaCl induced KCl and NaHCO3 intake that was not inhibited by gavage with gastric protectors Al(OH)3 or NaHCO3. IG 2 M NaCl or gavage of 0.6 N acetic acid induced mild irritation, hyperemia, of the glandular part of the stomach. A gavage of 50% ethanol induced strong irritation seen as pinpoint ulcerations. Neither ethanol nor acetic acid induced any fluid intake. Neither IG 2 M NaCl nor acetic acid induced kaolin intake, a marker of pica in laboratory rats. Ethanol did induce kaolin intake. These results suggest that IG 2 M NaCl induced a mineral fluid intake not selective for sodium and independent from gastric irritation or pica. Copyright © 2011 Elsevier Inc. All rights reserved.

Triclosan Induces Thymic Stromal Lymphopoietin in Skin Promoting Th2 Allergic Responses

PubMed Central

Marshall, Nikki B.; Lukomska, Ewa; Long, Carrie M.; Kashon, Michael L.; Sharpnack, Douglas D.; Nayak, Ajay P.; Anderson, Katie L.; Meade, B. Jean; Anderson, Stacey E.

2016-01-01

Triclosan is an antimicrobial chemical incorporated into many personal, medical and household products. Approximately, 75% of the U.S. population has detectable levels of triclosan in their urine, and although it is not typically considered a contact sensitizer, recent studies have begun to link triclosan exposure with augmented allergic disease. We examined the effects of dermal triclosan exposure on the skin and lymph nodes of mice and in a human skin model to identify mechanisms for augmenting allergic responses. Triclosan (0%–3%) was applied topically at 24-h intervals to the ear pinnae of OVA-sensitized BALB/c mice. Skin and draining lymph nodes were evaluated for cellular responses and cytokine expression over time. The effects of triclosan (0%–0.75%) on cytokine expression in a human skin tissue model were also examined. Exposure to triclosan increased the expression of TSLP, IL-1β, and TNF-α in the skin with concomitant decreases in IL-25, IL-33, and IL-1α. Similar changes in TSLP, IL1B, and IL33 expression occurred in human skin. Topical application of triclosan also increased draining lymph node cellularity consisting of activated CD86+GL-7+ B cells, CD80+CD86+ dendritic cells, GATA-3+OX-40+IL-4+IL-13+ Th2 cells and IL-17 A+ CD4 T cells. In vivo antibody blockade of TSLP reduced skin irritation, IL-1β expression, lymph node cellularity, and Th2 responses augmented by triclosan. Repeated dermal exposure to triclosan induces TSLP expression in skin tissue as a potential mechanism for augmenting allergic responses. PMID:26048654

Screening for eye irritancy using cultured HeLa cells.

PubMed

Selling, J; Ekwall, B

1985-01-01

To investigate whether toxicity tests on HeLa cells were predictive of eye irritancy, 18 compounds of known eye irritancy and in vitro cytotoxicity were tested on HeLa cells in the MIT-24 system. The results correlated well with eye irritancy as determined by the Draize test in rabbits for 16 of the test substances, but failed to detect the high eye irritancy of 1-heptanol and allyl alcohol, both of which were cytotoxic in other cellular systems.

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

PubMed

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

2011-01-11

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

The potential benefits of using aloe vera in stoma patient skin care.

PubMed

Rippon, Mark; Perrin, Angie; Darwood, Richard; Ousey, Karen

2017-03-09

Individuals living with an ostomy may suffer from a variety of peri-stomal skin complications related to the use of their stoma appliance or accessories. These conditions can be serious enough to significantly impact on a patient's quality of life and may result in severe clinical complications (such as infection). This article is a review of the literature with the objective of investigating and presenting evidence for the well-documented use of aloe vera in the prevention of skin conditions similar to those seen in peri-stomal skin complications. An exploration for the potential use of aloe vera directly or indirectly (as an adjunct to medical devices such as wafers) in stoma patients is presented with the view that this use may be beneficial in the prevention of such peri-stomal skin complications.

Two-stage bottom-up tiered approach combining several alternatives for identification of eye irritation potential of chemicals including insoluble or volatile substances.

PubMed

Hayashi, Kazuhiko; Mori, Taeko; Abo, Takayuki; Ooshima, Kenichi; Hayashi, Takumi; Komano, Tomoko; Takahashi, Yutaka; Sakaguchi, Hitoshi; Takatsu, Akihiko; Nishiyama, Naohiro

2012-10-01

For the assessment of eye irritation, one alternative test may not completely replace the rabbit Draize test. In the present study, we examined the predictive potential of a tiered approach analyzing the results from several alternatives (i.e., the Short Time Exposure (STE) test, the EpiOcular assay, the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay and the Bovine Corneal Opacity and Permeability (BCOP) assay) for assessing Globally Harmonized System (GHS) eye irritation categories. Fifty-six chemicals including alcohols, surfactants, and esters were selected with a balanced GHS category and a wide range of chemical classes. From a standpoint of both assessable sample numbers and predictive accuracy, the more favorable tiered approach was considered to be the two-stage bottom-up tiered approach combining the STE test, the EpiOcular assay followed by the BCOP assay (accuracy 69.6%, under prediction rate 8.9%). Moreover, a more favorable predictive capacity (accuracy 71.4%, under prediction rate 3.6%) was obtained when high volatile alcohols/esters with vapor pressures >6 kilopascal (kPa) at 25°C were evaluated with EpiOcular assay instead of the STE test. From these results, the two-stage bottom-up tiered approach combining the STE test, the EpiOcular assay followed by the BCOP assay might be a promising method for the classification of GHS eye irritation category (Not classified (NC), Category 2 (Cat. 2), and Category 1 (Cat. 1)) for a wide range of test chemicals regardless of solubility. Copyright © 2012 Elsevier Ltd. All rights reserved.

Irritable bowel syndrome

MedlinePlus

... Side Effects of Drugs . 16th ed. Philadelphia, PA: Elsevier; 2016:488-494. Canavan C, West J, Card ... FF, ed. Ferri's Clinical Advisor 2018 . Philadelphia, PA: Elsevier; 2018:722-725. Ford AC, Talley NJ. Irritable ...

Evaluating the sensitization potential of surfactants: integrating data from the local lymph node assay, guinea pig maximization test, and in vitro methods in a weight-of-evidence approach.

PubMed

Ball, Nicholas; Cagen, Stuart; Carrillo, Juan-Carlos; Certa, Hans; Eigler, Dorothea; Emter, Roger; Faulhammer, Frank; Garcia, Christine; Graham, Cynthia; Haux, Carl; Kolle, Susanne N; Kreiling, Reinhard; Natsch, Andreas; Mehling, Annette

2011-08-01

An integral part of hazard and safety assessments is the estimation of a chemical's potential to cause skin sensitization. Currently, only animal tests (OECD 406 and 429) are accepted in a regulatory context. Nonanimal test methods are being developed and formally validated. In order to gain more insight into the responses induced by eight exemplary surfactants, a battery of in vivo and in vitro tests were conducted using the same batch of chemicals. In general, the surfactants were negative in the GPMT, KeratinoSens and hCLAT assays and none formed covalent adducts with test peptides. In contrast, all but one was positive in the LLNA. Most were rated as being irritants by the EpiSkin assay with the additional endpoint, IL1-alpha. The weight of evidence based on this comprehensive testing indicates that, with one exception, they are non-sensitizing skin irritants, confirming that the LLNA tends to overestimate the sensitization potential of surfactants. As results obtained from LLNAs are considered as the gold standard for the development of new nonanimal alternative test methods, results such as these highlight the necessity to carefully evaluate the applicability domains of test methods in order to develop reliable nonanimal alternative testing strategies for sensitization testing. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Ionic liquids as antimicrobials, solvents, and prodrugs for treating skin disease

NASA Astrophysics Data System (ADS)

Zakrewsky, Michael A.

The skin is the largest organ in the body. It provides a compliant interface for needle-free drug delivery, while avoiding major degradative pathways associated with the GI tract. These can result in improved patient compliance and sustained and controlled release compared to other standard delivery methods such as intravenous injection, subcutaneous injection, and oral delivery. Concurrently, for the treatment of skin related diseases (e.g. bacterial infection, skin cancer, psoriasis, atopic dermatitis, etc.) cutaneous application provides targeted delivery to the disease site, allowing the use of more potent therapeutics with fewer systemic side effects. Unfortunately, the outer layer of the skin -- the stratum corneum (SC) -- presents a significant barrier to most foreign material. This is particularly true for large hydrophilic molecules (>500Da), which must partition through tortuous lipid channels in the SC to penetrate deep tissue layers where the majority of skin-related diseases reside. Interestingly, over the last few decades ionic liquids (ILs) have emerged as a burgeoning class of designer solvents. ILs have been proven beneficial for use in industrial processing, catalysis, pharmaceuticals, and electrochemistry to name a few. The ability to modulate either the cation or anion individually presents an advantageous framework for tuning secondary characteristics without sacrificing the primary function of the IL. Here we report the use of novel ILs for cutaneous drug delivery. Specifically, we demonstrate their potential as potent, broad-spectrum antimicrobials, as solvents for topical delivery of hydrophilic and hydrophobic drugs, and as prodrugs to either reduce the dose-dependent toxicity of drugs that cause skin irritation or enhance delivery of macromolecules into skin and cells. Thus, our results clearly demonstrate ILs holds promise as a transformative platform for treating skin disease.

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

PubMed

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

2013-11-01

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

Additively Manufactured Pneumatically Driven Skin Electrodes.

PubMed

Schubert, Martin; Schmidt, Martin; Wolter, Paul; Malberg, Hagen; Zaunseder, Sebastian; Bock, Karlheinz

2017-12-23

Telemedicine focuses on improving the quality of health care, particularly in out-of-hospital settings. One of the most important applications is the continuous remote monitoring of vital parameters. Long-term monitoring of biopotentials requires skin-electrodes. State-of-the-art electrodes such as Ag/AgCl wet electrodes lead, especially during long-term application, to complications, e.g., skin irritations. This paper presents a low-cost, on-demand electrode approach for future long-term applications. The fully printed module comprises a polymeric substrate with electrodes on a flexible membrane, which establishes skin contact only for short time in case of measurement. The membranes that produce airtight seals for pressure chambers can be pneumatically dilated and pressed onto the skin to ensure good contact, and subsequently retracted. The dilatation depends on the pressure and membrane thickness, which has been tested up to 150 kPa. The electrodes were fabricated in screen and inkjet printing technology, and compared during exemplary electrodermal activity measurement (EDA). The results show less amplitude compared to conventional EDA electrodes but similar behavior. Because of the manufacturing process the module enables high individuality for future applications.

Increased skin barrier disruption by sodium lauryl sulfate in mice expressing a constitutively active STAT6 in T cells.

PubMed

DaSilva, Sonia C; Sahu, Ravi P; Konger, Raymond L; Perkins, Susan M; Kaplan, Mark H; Travers, Jeffrey B

2012-01-01

Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease that affects 10-20% of children and 1-3% of adults worldwide. Recent studies have indicated that the ability of Th2 cytokines, such as interleukin-4 (IL-4) to regulate skin barrier function may be a predisposing factor for AD development. The present studies examined the ability of increased Th2 activity to affect cutaneous barrier function in vivo and epidermal thickening. Mice that express a constitutively active Signal Transducer and Activator of Transcription 6 (STAT6VT) have increased Th2 cells and a predisposition to allergic inflammation were used in these studies, they demonstrate that topical treatment with the irritant sodium lauryl sulfate (SLS) caused increased transepidermal water loss and epidermal thickening in STAT6VT mice over similarly treated wild-type mice. The proliferation marker Ki-67 was increased in the epidermis of STAT6VT compared to the wild-type mice. However, these differences do not appear to be linked to the addition of an irritant as control-treated STAT6VT skin also exhibited elevated Ki-67 levels, suggesting that the increased epidermal thickness in SLS-treated STAT6VT mice is primarily driven by epidermal cell hypertrophy rather than an increase in cellular proliferation. Our results suggest that an environment with increased Th2 cytokines results in abnormal responses to topical irritants.

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

PubMed

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

2014-12-01

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

Diesel exhaust causing low-dose irritant asthma with latency?

PubMed

Adewole, Femi; Moore, Vicky C; Robertson, Alastair S; Burge, P S

2009-09-01

Diesel exhaust exposure may cause acute irritant-induced asthma and potentiate allergen-induced asthma. There are no previous reports of occupational asthma due to diesel exhaust. To describe occupational asthma with latency in workers exposed to diesel exhaust in bus garages. The Shield database of occupational asthma notifications in the West Midlands, UK, was searched between 1990 and 2006 for workers where diesel exhaust exposure was thought to be the cause of the occupational asthma. Those without other confounding exposures whose occupational asthma was validated by serial peak expiratory flow (PEF) analysis using Oasys software were included. Fifteen workers were identified with occupational asthma attributed to diesel exhaust. Three had validated new-onset asthma with latency. All worked in bus garages where diesel exhaust exposure was the only likely cause of their occupational asthma. Occupational asthma was confirmed by measures of non-specific reactivity and serial measurements of PEF with Oasys scores of 2.9, 3.73 and 4 (positive score > 2.5). The known non-specific irritant effects of diesel exhaust suggest that this is an example of low-dose irritant-induced asthma and that exposures to diesel exhaust in at least some bus garages are at a sufficient level to cause this.

A cross-cultural perspective on irritable bowel syndrome.

PubMed

Gerson, Charles D; Gerson, Mary-Joan

2010-01-01

Irritable bowel syndrome is a functional gastrointestinal illness, defined by symptoms. Irritable bowel syndrome has been described as a biopsychosocial condition, in which colonic dysfunction is affected by psychological and social factors. As a result of this unusual constellation, irritable bowel syndrome may be subject to cultural variables that differ in different parts of the globe. In this article, we describe some of the ways in which irritable bowel syndrome may be experienced differently, depending on local belief systems, psychological pressures, acceptance or resistance to a mind-body paradigm, and breakdown in support or relationship structure. Examples are given in which irritable bowel syndrome investigators from countries around the world describe various aspects of the syndrome that may affect the illness experience of their patients. We describe our own research studies that have demonstrated possible adverse effects on disease severity from relationship conflict, attribution of symptoms to physical rather than emotional cause, and the belief that irritable bowel syndrome is enduring and mysterious. Also described is our finding that symptom patterns may differ significantly between different geographic locations. Finally, we discuss the importance of "cultural competence" on the part of healthcare professionals in regard to caring for patients of diverse cultural backgrounds. © 2010 Mount Sinai School of Medicine.

Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Irritability in Autistic Children

PubMed Central

Kirino, Eiji

2014-01-01

Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed. PMID:24932108

Tretinoin for the treatment of photodamaged skin.

PubMed

Ting, William

2010-07-01

Interest in and interventions for photodamaged skin have dramatically increased over the last few years. Although a number of topical therapies have been used for the treatment of photodamaged skin, many therapies remain unproven in efficacy, unapproved, or only supported with limited clinical evidence. Topical retinoids, particularly tretinoin, are the most extensively studied. They have been shown to attenuate and reverse the signs of photodamage, such as coarse wrinkling. In addition, the clinical changes achieved with tretinoin are accompanied by histologic evidence of benefit. The main drawbacks to retinoid use are local irritation and erythema that can limit utility in some patients. New retinoids and formulations specifically optimized to improve cutaneous tolerability have been introduced. Two case reports of patients using low-concentration tretinoin gel 0.05% for the treatment of photodamaged skin are discussed. Over a relatively short treatment period of 4 weeks, tretinoin gel 0.05% was shown to provide both chemoprevention and reversal of photodamage.

Evaluation of a cyanoacrylate dressing to manage peristomal skin alterations under ostomy skin barrier wafers.

PubMed

Milne, Catherine T; Saucier, Darlene; Trevellini, Chenel; Smith, Juliet

2011-01-01

Peristomal skin alterations under ostomy barrier wafers are a commonly reported problem. While a number of interventions to manage this issue have been reported, the use of a topically applied cyanoacrylate has received little attention. This case series describes the use of a topical cyanoacrylate for the management of peristomal skin alterations in persons living with an ostomy. Using a convenience sample, the topical cyanoacrylate dressing was applied to 11 patients with peristomal skin disruption under ostomy wafers in acute care and outpatient settings. The causes of barrier function interruption were also addressed to enhance outcomes. Patients were assessed for wound discomfort using a Likert Scale, time to healing, and number of appliance changes. Patient satisfaction was also examined. Average reported discomfort levels were 9.5 out of 10 at the initial peristomal irritation assessment visit decreased to 3.5 at the first wafer change and were absent by the second wafer change. Wafers had increasing wear time between changes in both settings with acute care patients responding faster. Epidermal resurfacing occurred within 10.2 days in outpatients and within 7 days in acute care patients. Because of the skin sealant action of this dressing, immediate adherence of the wafer was reported at all pouch changes.

Complementary and alternative medicine for treatment of irritable bowel syndrome.

PubMed

Shen, Yi-Hao A; Nahas, Richard

2009-02-01

To review the evidence supporting selected complementary and alternative medicine approaches used in the treatment of irritable bowel syndrome (IBS). MEDLINE (from January 1966), EMBASE (from January 1980), and the Cochrane Database of Systematic Reviews were searched until March 2008, combining the terms irritable bowel syndrome or irritable colon with complementary therapies, alternative medicine, acupuncture, fiber, peppermint oil, herbal, traditional, yoga, massage, meditation, mind, relaxation, probiotic, hypnotherapy, psychotherapy, cognitive therapy, or behavior therapy. Results were screened to include only clinical trials, systematic reviews, and meta-analyses. Level I evidence was available for most interventions. Soluble fibre improves constipation and global IBS symptoms. Peppermint oil alleviates IBS symptoms, including abdominal pain. Probiotic trials show overall benefit for IBS but there is little evidence supporting the use of any specific strain. Hypnotherapy and cognitive-behavioural therapy are also effective therapeutic options for appropriate patients. Certain herbal formulas are supported by limited evidence, but safety is a potential concern. All interventions are supported by systematic reviews or meta-analyses. Several complementary and alternative therapies can be recommended as part of an evidence-based approach to the treatment of IBS; these might provide patients with satisfactory relief and improve the therapeutic alliance.

Studies on the cellular and subcellular reactions in epidermis at irritant and allergic dermatitis.

PubMed

Lindberg, M

1982-01-01

To determine the cellular and subcellular reactions of keratinocytes at contact dermatitis, transmission electron microscopy was used in combination with energy dispersive X-ray microanalysis. Stereology and optical diffraction were used as complements to electron microscopy for studies of the effects of variations in the preparation technique on the ultrastructure of epidermis. The morphological effects of an increased hydration of epidermis were assessed by the use of occlusive patch tests. It was found that the relative volume of the epidermal intercellular space and the ultrastructure of the epidermal cells (keratinocytes and Langerhans' cells) were directly dependent on the osmolality of the fixative vehicle if glutaraldehyde was used as fixative. Cellular volume and morphology did also depend on the fixative used. Variations in the volume of the intercellular space were also detected when the water transport through epidermis was impaired by occlusive treatment. In normal epidermis prolonged fixation times (4 weeks) did not affect the morphology of the keratinocytes. However, if the structure and function of the keratinocytes were affected by the application of a irritant substance (DNCB), a loss of electron dense material from the cells was detected within 3 weeks. The ultrastructural changes in the keratinocytes at the irritant chromate and DNCB reactions were of a non-specific nature and are in accordance with the changes described for other irritant agents in the literature. A few cells with the features of apoptosis were recorded. The allergic chromate reaction was found to be a combination of the irritant reaction and a marked inflammatory response. To correlate the ultrastructural alterations in the keratinocytes with the functional state of the cells, X-ray microanalysis was used to determine the elemental redistribution occurring at the irritant DNCB reaction. The results of the X-ray microanalysis showed a good correlation between dose and time

Skin reaction and regeneration after single sodium lauryl sulfate exposure stratified by filaggrin genotype and atopic dermatitis phenotype.

PubMed

Bandier, J; Carlsen, B C; Rasmussen, M A; Petersen, L J; Johansen, J D

2015-06-01

Filaggrin is key for the integrity of the stratum corneum. Mutations in the filaggrin gene (FLGnull) play a prominent role in atopic dermatitis (AD) pathogenesis. People with AD have increased susceptibility to irritants. However, little is known about the effect of filaggrin genotype and AD phenotype on irritant response and skin regeneration. To investigate the role of FLGnull and AD groups for skin reaction and recovery after sodium lauryl sulfate (SLS) irritation. This is a case-control study comprising 67 subjects, including healthy controls and patients with and without FLGnull and AD. Reactivity to different doses of SLS at 24, 48, 72 and 145 h after SLS application was measured by transepidermal water loss (TEWL) and laser Doppler flowmetry (LDF). Reactivity was assessed univariately and by pattern analysis. All patient groups showed a higher degree of skin-barrier disruption and inflammation than did controls in response to SLS. Assessing reactivity by the delta value of the area under the curve for both TEWL and LDF showed significant differences between healthy controls and those with the AD phenotype, irrespective of filaggrin mutation. The poorest regeneration was among those with the AD phenotype. The two AD phenotype groups were separated by multivariate technique, due to earlier inflammatory reactivity among subjects with FLGnullplus AD compared with the AD phenotype alone. Both skin reaction and regeneration were significantly different between the patient population and the healthy controls. Additionally, response severity and regeneration depended more on AD phenotype than on filaggrin genotype, whereas the response was more rapid among the FLGnullplus AD individuals. © 2015 British Association of Dermatologists.

Irritable Bowel Syndrome

MedlinePlus

Irritable bowel syndrome (IBS) is a problem that affects the large intestine. It can cause abdominal cramping, bloating, and a change in bowel ... go back and forth between the two. Although IBS can cause a great deal of discomfort, it ...

Antioxidant Therapies for Ulcerative Dermatitis: A Potential Model for Skin Picking Disorder

PubMed Central

George, Nneka M.; Whitaker, Julia; Vieira, Giovana; Geronimo, Jerome T.; Bellinger, Dwight A.; Fletcher, Craig A.; Garner, Joseph P.

2015-01-01

Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine’s mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly

Antioxidant Therapies for Ulcerative Dermatitis: A Potential Model for Skin Picking Disorder.

PubMed

George, Nneka M; Whitaker, Julia; Vieira, Giovana; Geronimo, Jerome T; Bellinger, Dwight A; Fletcher, Craig A; Garner, Joseph P

2015-01-01

Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine's mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly tolerated

NDELA and nickel modulation of triazine disposition in skin.

PubMed

Baynes, Ronald E; Brooks, James D; Barlow, Beth M; Riviere, Jim E

2005-10-01

Cutting fluids can become contaminated with metals (e.g., nickel, Ni) and nitrosamines (e.g., N-nitrosodiethanolamine, NDELA) and there is concern that these classes of contaminants can modulate dermal disposition and ultimately the toxicity of cutting fluid additives, such as irritant biocides (e.g., triazine). Biocides are added to these formulations to prevent bacterial degradation of commercial cutting fluids. The purpose of this study was to assess the dermal absorption and skin deposition of 14C-triazine when topically applied to porcine skin in an in vitro flow-through diffusion cell system as aqueous soluble oil (mineral oil, MO) or aqueous synthetic (polyethylene glycol, PEG) mixtures. 14C-Triazine mixtures were formulated with NDELA and/or Ni, or with a combination of three additional cutting fluid additives; namely, 5% linear alkylbenzene sulfonate (LAS), 5% triethanolamine (TEA) and 5% sulfurized ricinoleic acid. Neither Ni nor NDELA was absorbed during these 8-h studies. However, 14C-triazine absorption ranged from 2.72 to 3.29% dose in MO and 2.29-2.88% dose in PEG with significantly greater triazine absorption in MO than PEG when all additives and contaminates were present. The difference between these two diluents was most pronounced when NDELA and/or Ni were present in cutting fluids. These contaminants also enhanced triazine deposition on the skin surface and skin tissues especially with PEG-based mixtures. In essence, the dermal disposition of irritant biocides could be dependent on whether the worker is exposed to a soluble oil or synthetic fluid when these contaminants are present. Workers should therefore not only be concerned about dermatotoxicity of these contaminants, but also the modulated dermal disposition of cutting fluid additives when these contaminants are present in cutting fluid formulations.

The impact of intolerance of uncertainty, worry and irritability on quality of life in persons with epilepsy: irritability as mediator.

PubMed

Barahmand, Usha; Haji, Afsar

2014-10-01

Epilepsy is a neurological disorder afflicting many people in the world. The impact of epilepsy on the quality of life of those afflicted with epilepsy is greater than the limitations imposed by the seizures alone. Among the several psychological disorders found to be comorbid with epilepsy are anxiety and depression, both of which impair quality of life in epilepsy. Some studies have reported that the anxiety seen in epilepsy is characterized by worry while the depression seen is characterized by irritability. A concept common to both anxiety and depression is intolerance of uncertainty. Therefore, the study explores the relationship between intolerance of uncertainty, worry and irritability and their association to quality of life in epilepsy. A descriptive-correlational research method was used and the research sample comprised 60 consecutive referrals seeking outpatient neurological services for epilepsy at Alavi Hospital in Ardebil. Data were collected by administering the Penn State Worry Questionnaire, Intolerance of Uncertainty Scale, Irritability Questionnaire and Quality of Life in Epilepsy Inventory. Data were analyzed using Pearson's correlation coefficients and multivariate regression analysis. Mediation and moderation analyses were conducted. Findings indicated that intolerance of uncertainty, worry and irritability have unique significant effects on quality of life. The implications are that interventions aimed at improving the quality of life of patients with epilepsy should address their feelings of uncertainty, worry and irritability. Furthermore, irritability seems to mediate the impact of both intolerance of uncertainty and worry on quality of life of individuals with epilepsy. No significant moderation effects were noted. Results underscore the important role of irritability in the quality of life of persons with epilepsy. The findings are discussed with reference to the possibility of particular predisposing temperaments and add credence to

A new 3D reconstituted human corneal epithelium model as an alternative method for the eye irritation test.

PubMed

Jung, Kyoung-Mi; Lee, Su-Hyon; Ryu, Yang-Hwan; Jang, Won-Hee; Jung, Haeng-Sun; Han, Ju-Hee; Seok, Seung-Hyeok; Park, Jae-Hak; Son, Youngsook; Park, Young-Ho; Lim, Kyung-Min

2011-02-01

Many efforts are being made to develop new alternative in vitro test methods for the eye irritation test. Here we report a new reconstructed human corneal epithelial model (MCTT HCE model) prepared from primary-cultured human limbal epithelial cells as a new alternative in vitro eye irritation test method. In histological and immunohistochemical observation, MCTT HCE model displayed a morphology and biomarker expressions similar to intact human cornea. Moreover, the barrier function was well preserved as measured by high transepithelial electrical resistance, effective time-50 for Triton X-100, and corneal thickness. To employ the model as a new alternative method for eye irritation test, protocol refinement was performed and optimum assay condition was determined including treatment time, treatment volume, post-incubation time and rinsing method. Using the refined protocol, 25 reference chemicals with known eye irritation potentials were tested. With the viability cut-off value at 50%, chemicals were classified to irritant or non-irritant. When compared with GHS classification, the MCTT HCE model showed the accuracy of 88%, sensitivity of 100% and specificity of 77%. These results suggest that the MCTT HCE model might be useful as a new alternative eye irritation test method. Copyright © 2010 Elsevier Ltd. All rights reserved.

Simultaneous measurement of skin potential and conductance in electrodermal response monitoring

NASA Astrophysics Data System (ADS)

Jabbari, A.; Johnsen, B.; Grimnes, S.; Martinsen, Ø. G.

2010-04-01

Measurement of electrodermal activity (EDA) has been an important tool in psychophysiological research. The emotional sweat activity is very sensitive to psychological stimuli or conditions. The changes are easily detected by means of electrical measurements and since the sweat ducts are predominantly resistive, a low-frequency conductance measurement is appropriate for measurement of skin conductance in electrodermal response. The main purpose of this study was to develop a measuring system where DC current was replaced by a small AC current in a system so the DC potential and AC conductance could be measured simultaneously at the same skin site. A small, battery operated, PDA based instrument has been developed. The preliminary results of this ongoing study show that there is additional information in the DC potential channel and that different stimuli seem to produce slightly different response patterns.

Potential Allergens in Disposable Diaper Wipes, Topical Diaper Preparations, and Disposable Diapers: Under-recognized Etiology of Pediatric Perineal Dermatitis.

PubMed

Yu, JiaDe; Treat, James; Chaney, Keri; Brod, Bruce

2016-01-01

Allergic contact dermatitis in young children may be an under-recognized cause of perineal dermatitis. The diapered infant skin is uniquely susceptible to allergic contact dermatitis because of more permeable neonatal skin, a moist environment, frequent contact with irritants and resultant skin barrier breakdown, and exposure to topical products such as diaper wipes, diaper preparations, and disposable diapers. To our knowledge, potential allergens in these products have not been thoroughly catalogued or studied. We explore and review potential allergenic ingredients in diaper wipes, topical diaper preparations, and disposable diapers. We analyzed 63 diaper wipes, 41 topical diaper preparations, and the 3 top selling diaper brands available from two of the largest retailers in the United States. Each potential allergen is discussed, and epidemiologic studies of rates of sensitization to potential allergens in children are also reported. Botanical extracts, including members of the Compositae family, were the most commonly represented potential allergen in both diaper wipes and topical preparations. Other potential allergens identified with high frequency include α-tocopherol, fragrances, propylene glycol, parabens, iodopropynyl butylcarbamate, and lanolin. Frequent culprits such as formaldehyde releasers and methylchloroisothiazolinone/methylisothiazolinone were not prevalent in our analyzed products.

Communicating the location of potential skin neoplasms for excision between the referring and the operating doctor--an audit of skin lesion referrals in Whanganui, New Zealand.

PubMed

Welsh, Fraser; Bullen, Naomi; Aiono, Semisi

2013-08-30

The importance of correctly defining the location of potential skin cancer when surgical treatment may be required is self-evident. Clear communication is essential if the professional diagnosing potential skin cancer is not the same professional providing treatment. We aimed to assess the nature of the localising information provided in referrals to the local anaesthetic skin lesion theatre in our institution. Information localising target lesions for new patients seen in our local anaesthetic skin excision theatre was recorded during a 2-month period April to May 2012 inclusive 100 patients were seen in our skin excision theatre during the study period; 16 patients were not able to identify the target skin lesion at the time they entered the operating theatre. The target lesion could not be determined from the referral text in 30/100 cases. Diagrams were provided in 19/100 cases. Photographs were provided in 3/100 cases. Pictorial and photographic means of communicating the location of suspicious lesions are under-utilised in our service. Relying on the patient or the referral text to correctly identify the lesion leaves considerable room for error. We suggest that photographic information for skin lesion referrals is adopted as a minimum standard.

Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model.

PubMed

Kaluzhny, Yulia; Kandárová, Helena; d'Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

2015-08-23

To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492.

Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

PubMed Central

Kaluzhny, Yulia; Kandárová, Helena; d’Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

2015-01-01

To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492. PMID:26325674

Cosmeceutical effect of ethyl acetate fraction of Kombucha tea by intradermal administration in the skin of aged mice.

PubMed

Pakravan, Nafiseh; Mahmoudi, Elaheh; Hashemi, Seyed-Ali; Kamali, Jamal; Hajiaghayi, Reza; Rahimzadeh, Mitra; Mahmoodi, Vajiheh

2017-11-19

Natural ingredients have been always an interesting approach to prolong youthful appearance of skin. One of the natural compounds is Kombucha tea (KT), which has been mainly used as an energy drink in Asian countries for a long time. Previous reports indicated that it has pharmaceutical and favorable wound repairing effects. The beneficial properties of KT are thought to be mainly due to the presence of fermentation products such as flavonoids and other polyphenols with inhibition of hydrolytic and oxidative enzymes and anti-inflammatory effects. These properties prompted us to study the anti-aging potential of KT and investigate its effective fraction in aged mice, METHODS: Kombucha tea was fractionated into chloroform, butanol, and ethyl acetate, and flavonoid content was determined. Young and old mice were used as control. KT ethyl acetate fraction (KEAf), which had the highest flavonoid content, was intradermally administered to old mice. Administration of KEAf significantly increased the collagen content, NAD + /NADH level, and concomitantly improved skin connective tissue abnormalities in the aged skin. No sensitivity or irritation was observed. This finding suggested that KEAf can be a suitable candidate as a cosmetic product to improve aging-related skin abnormalities and regeneration of aged skin. © 2017 Wiley Periodicals, Inc.

Probiotic Therapy for Irritable Bowel Syndrome

PubMed Central

Aragon, George; Graham, Deborah B.; Borum, Marie

2010-01-01

The etiology of irritable bowel syndrome (IBS) is thought to be multifactorial, with several factors (including alterations in gut motility, small-bowel bacterial overgrowth, microscopic inflammation, and visceral hypersensitivity) potentially playing a role. Recent studies have suggested that probiotics may be useful in the treatment of IBS. Although the exact mechanism for how probiotics may aid in the reduction of symptoms commonly found in IBS is unknown, the effects of probiotics on alterations in gut bacteria appear to play a part. This review focuses on recent studies examining the role of probiotics in the treatment of IBS. PMID:20567539

Optimizing skin protection with semipermeable gloves.

PubMed

Wulfhorst, Britta; Schwanitz, Hans Joachim; Bock, Meike

2004-12-01

Occlusion due to gloves is one important cause of glove irritation. Macerated softened skin gives poor protection against microbes and chemical injuries. The introduction of a breathable protective glove material would represent a significant step toward improved prevention of occupational skin disease. Performance levels of semipermeable and occlusive gloves were examined under conditions typical of the hairdressing profession. In two studies, tests comparing breathable semipermeable gloves to single-use gloves made of occlusive materials were conducted. In an initial study, a user survey was carried out in conjunction with bioengineering examinations. Values at baseline and values after gloves were worn were recorded by measuring transepidermal water loss (TEWL), skin humidity (SH), and skin surface hydrogen ion concentration (pH) in 20 healthy volunteers. In a second study, the gloves were tested for penetrability and permeability with three chemical compounds typically used in the hairdressing profession. Bioengineering examination objectively confirmed users' reports of reduced hand perspiration when semipermeable gloves were worn. The TEWL, SH, and skin surface pH values remained largely stable after 20 minutes of wearing semipermeable gloves, in contrast to the reactions observed with gloves of occlusive materials. Permeability tests indicated that the semipermeable material is effective, with some restrictions. Air leakage testing revealed that all 50 gloves tested were not airtight. Following the optimization of manufacturing methods, additional tests of the penetrability of semipermeable gloves will be necessary.

In vitro and in vivo assessment of the effect of Laurus novocanariensis oil and essential oil in human skin.

PubMed

Viciolle, E; Castilho, P; Rosado, C

2012-12-01

Laurus novocanariensis is an endemic plant from the Madeira Island forest that derives a fatty oil, with a strong spicy odour, from its berries that has been used for centuries in traditional medicine to treat skin ailments. This work aimed to investigate the effect of the application of both the oil and its essential oil on normal skin, to assess their safety and potential benefits. Diffusion studies with Franz cells using human epidermal membranes were conducted. The steady-state fluxes of two model molecules through untreated skin were compared with those obtained after a 2-h pre-treatment with either the oil or the essential oil. Additionally, eleven volunteers participated in the in vivo study that was conducted on the forearm and involved daily application of the oil for 5 days. Measurements were performed every day in the treated site with bioengineering methods that measure erythema, irritation and loss of barrier function. Slightly higher steady-state fluxes were observed for both the lipophilic and the hydrophilic molecule when the epidermal membranes were pre-treated. Nevertheless, such differences had no statistical significance, which seems to confirm that neither the oil nor the essential oil impaired the epidermal barrier. Results collected with the Chromameter, the Laser Doppler Flowmeter and the visual scoring are in agreement with those established in the in vitro study. They indicate that the repeated application of the oil did not cause erythema, because the results observed in the first day of the study were maintained throughout the week. Application of the oil did not affect the skin barrier function, because the transepidermal water loss remained constant throughout the study. The stratum corneum hydration was slightly reduced on days 4 and 5. This work shows that both the oil and the essential oil were well tolerated by the skin and did not cause significant barrier impairment or irritation. © 2012 Society of Cosmetic Scientists and the

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.

Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin.

PubMed

Raza, Kaisar; Singh, Bhupinder; Mahajan, Anadi; Negi, Poonam; Bhatia, Amit; Katare, O P

2011-05-01

Capsaicin, extracted from the fruits of Capsicum, is a powerful local stimulant with strong rubifacient action, devoid of vesication. Topical use of capsaicin is quite common in the treatment of various pain-associated musculo-skeletal disorders, itching and neuropathy. Despite its high pharmacodynamic potential, the patient compliance to the drug is reported to be poor owing to multiple skin problems like irritation, burning sensation, and erythma. The present study targets the encasement of drug in the interiors of flexible membrane vesicles (FMVs), as these are reported to have better penetration in the deeper layers of skin, thus leading to enhanced localization of drug and consequently, decreased skin irritation. Multilamellar drug-loaded FMVs, prepared by thin-film hydration were evaluated for their efficacy in vitro and in vivo. When compared with conventional liposomes, the formulated FMVs showed higher skin retention during ex vivo permeation studies employing LACA mice skin, higher analgesic potential using radiant tail-flick method in mice, and better flexibility in regaining their size. Being less of an irritant, these vesicular carriers were also found to be more comfortable on human skin. Thus, the capsaicin-loaded FMVs offer high potential as topical drug delivery technologies with improved patient acceptance and effectiveness.

Increased skin barrier disruption by sodium lauryl sulfate in mice expressing a constitutively active STAT6 in T cells

PubMed Central

DaSilva, Sonia C.; Sahu, Ravi P.; Konger, Raymond L.; Perkins, Susan M.; Kaplan, Mark H.; Travers, Jeffrey B.

2011-01-01

Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease that affects 10–20% of children and 1–3% of adults worldwide. Recent studies have indicated that the ability of Th2 cytokines such as interleukin-4 (IL-4) to regulate skin barrier function may be a predisposing factor for AD development. The present studies examined the ability of increased Th2 activity to affect cutaneous barrier function in vivo and epidermal thickening. Mice that express a constitutively active Signal Transducer and Activator of Transcription 6 (STAT6VT) have increased Th2 cells and a predisposition to allergic inflammation were used in these studies; they demonstrate that topical treatment with the irritant sodium lauryl sulfate (SLS) caused increased transepidermal water loss and epidermal thickening in STAT6VT mice over similarly treated wild-type mice. The proliferation marker Ki-67 was increased in the epidermis of STAT6VT compared to wild-type mice. However, these differences do not appear to be linked to the addition of an irritant as control-treated STAT6VT skin also exhibited elevated Ki-67 levels, suggesting that the increased epidermal thickness in SLS-treated STAT6VT mice is primarily driven by epidermal cell hypertrophy rather than an increase in cellular proliferation. Our results suggest that an environment with increased Th2 cytokines results in abnormal responses to topical irritants. PMID:21959772

Medical adhesive-related skin injuries associated with vascular access.

PubMed

Hitchcock, Jan; Savine, Louise

2017-04-27

Establishing vascular access and preventing infection, both at insertion and during ongoing care is generally the top priority; the maintenance of optimal skin integrity is often a distant secondary consideration. Skin can react to different types of dressings or adhesives, or problems can arise relating to the securement of lines or the development of sensitivities to cleaning solutions. Clearly, these scenarios are not limited to the securement of vascular access devices; however, a patient with a long-term vascular access device may not have other options for vascular access, which makes this a very important and yet largely unrecognised area. A review of the limited literature that existed up to March 2015 showed it was typically concerned with skin tears connected with dressings and removal, and contact irritant dermatitis. The tissue viability team and vascular access team reviewed the current products associated with a typical vascular access dressing to ensure it was fit for purpose and where at all possible had good scientific literature for validation. The team worked proactively to recognise those patients at risk with the early identification of potential medical adhesive-related skin injuries (MARSI). To facilitate this an algorithm was developed that offers a step-by-step approach, clearly outlining what to do to prevent MARSI and its treatment should it develop. These reactions can result from other factors than the dressing alone, and an increase in these kinds of skin reaction in patients who are on chemotherapy regimens is being explored further. Through the implementation of an algorithm, education for both staff and patients and collaborative working between vascular access and tissue viability teams, a reduction in these phenomena has been seen despite an increasing number of at-risk patients.

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

PubMed

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

2007-03-01

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

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.

CON4EI: Development of testing strategies for hazard identification and labelling for serious eye damage and eye irritation of chemicals.

PubMed

Adriaens, E; Verstraelen, S; Alépée, N; Kandarova, H; Drzewiecka, A; Gruszka, K; Guest, R; Willoughby, J A; Van Rompay, A R

2018-06-01

Assessment of acute eye irritation potential is part of the international regulatory requirements for safety testing of chemicals. In the last decades, many efforts have been made in the search for alternative methods to replace the regulatory in vivo Draize rabbit eye test (OECD TG 405). Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. The main objective of the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for serious eye damage and eye irritation assessment that can lead to complete replacement of OECD TG 405. A set of 80 reference chemicals (e.g. balanced by important driver of classification and physical state), was tested with seven test methods. Based on the results of this project, three different strategies were suggested. We have provided a standalone (EpiOcular ET-50), a two-tiered and three-tiered strategy, that can be used to distinguish between Cat 1 and Cat 2 chemicals and chemicals that do not require classification (No Cat). The two-tiered and three-tiered strategies use an RhCE test method (EpiOcular EIT or SkinEthic™ EIT) at the bottom (identification No Cat) in combination with the BCOP LLBO (two-tiered strategy) or BCOP OP-KIT and SMI (three-tiered strategy) at the top (identification Cat 1). For our proposed strategies, 71.1% - 82.9% Cat 1, 64.2% - 68.5% Cat 2 and ≥80% No Cat chemicals were correctly identified. Also, similar results were obtained for the Top-Down and Bottom-Up approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of alimentation in irritable bowel syndrome.

PubMed

Dapoigny, M; Stockbrügger, R W; Azpiroz, F; Collins, S; Coremans, G; Müller-Lissner, S; Oberndorff, A; Pace, F; Smout, A; Vatn, M; Whorwell, P

2003-01-01

Different food items are made responsible for irritable bowel syndrome (IBS) symptoms, but the physiopathology of IBS remains unclear. During a meeting in Nice, France, experts of the European Working Team of the IBiS Club discussed selected data regarding the relationships between alimentation, food items (including fibers) and IBS symptoms. Food allergy remains a difficult diagnosis, but medical and general history, presence of general symptoms such as skin rash, and hypersensitivity tests may help in achieving a positive diagnosis. On the other hand, food intolerance is more confusing because of the subjectivity of the relationship between ingestion of certain foods and the appearance of clinical symptoms. Different food items which are commonly implicated in adverse reactions mimicking IBS were found to be stimulants for the gut, suggesting that patients with predominant diarrhea IBS have to be carefully questioned about consumption of different kinds of food (i.e., coffee, alcohol, chewing gum, soft drinks) and not only on lactose ingestion. Gas production is discussed on the basis of retention of intestinal gas as well as on malabsorption of fermentable substrates. The role of a large amount of this kind of substrate reaching the colon is suggested as a potential mechanism of IBS-type symptoms in overeating patients. Regarding the role of fiber in IBS, the expert group concluded that fibers are not inert substances and that they could trigger pain or bloating in some IBS patients. Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dieteticians may have a positive role in managing such patients. Copyright 2003 S. Karger AG, Basel

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

PubMed

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

2016-05-01

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

Evaluation of pH of Bathing Soaps and Shampoos for Skin and Hair Care.

PubMed

Tarun, Jose; Susan, Jose; Suria, Jacob; Susan, Veronica John; Criton, Sebastian

2014-09-01

Normal healthy skin has potential of hydrogen (pH) range of 5.4-5.9 and a normal bacterial flora. Use of soap with high pH causes an increase in skin pH, which in turn causes an increase in dehydrative effect, irritability and alteration in bacterial flora. The majority of soaps and shampoos available in the market do not disclose their pH. The aim of this study was to assess the pH of different brands of bathing soaps and shampoos available in the market. The samples of soaps and shampoos were collected from shops in the locality. The samples of different brands are coded before the analysis of the pH. Solution of each sample was made and pH was measured using pH meter. Majority of the soaps have a pH within the range of 9-10. Majority of the shampoos have a pH within the range of 6-7. The soaps and shampoos commonly used by the population at large have a pH outside the range of normal skin and hair pH values. Therefore, it is hoped that before recommending soap to patient especially those who have sensitive and acne prone skin, due consideration is given to the pH factor and also that manufacturers will give a thought to pH of soaps and shampoos manufactured by them, so that their products will be more skin and hair friendly.

Normative Irritability in Youth: Developmental Findings From the Great Smoky Mountains Study.

PubMed

Copeland, William E; Brotman, Melissa A; Costello, E Jane

2015-08-01

The goal of this study is to examine the developmental epidemiology of normative irritability and its tonic and phasic components in a longitudinal community sample of youth. Eight waves of data from the prospective, community Great Smoky Mountains Study (6,674 assessments of 1,420 participants) were used, covering children in the community 9 to 16 years of age. Youth and 1 parent were interviewed using the Child and Adolescent Psychiatric Assessment to assess tonic (touchy/easily annoyed, irritable mood, angry or resentful) and phasic (temper tantrums or anger outbursts) components of irritability, including frequency, duration, onset, and cross-context variability. At any given point in childhood/adolescence, 51.4% (standard error [SE] = 1.4) of participants reported phasic irritability, 28.3% (SE = 1.2) reported tonic irritability, and 22.8% (SE = 1.1) reported both. These prevalence levels decreased with age but did not vary by sex. The overlap between tonic and phasic irritability was high (odds ratio = 5.8, 95% CI = 3.3-10.5, p < .0001), with little evidence of tonic occurring without phasic irritability. Both tonic and phasic irritability predicted one another over time, supporting both heterotypic and homotypic continuity. Low levels of either tonic or phasic irritability increased risk for disrupted functioning including service use, school suspensions, parental burden, and emotional symptoms both concurrently and at 1-year follow-up. Irritability is relatively common, decreases with age but does not vary by sex, and at almost any level is associated with increased risk of disrupted functioning. Its relative components frequently overlap, although irritable outbursts are more common than irritable mood. Irritability appears to be a high-priority transdiagnostic marker for screening children in need of clinical attention. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Prevention of Dengue fever through plant based mosquito repellent Clausena dentata (Willd.) M. Roem (Family: Rutaceae) essential oil against Aedes aegypti l. (Diptera: Culicidae) mosquito.

PubMed

Rajkumar, S; Jebanesan, A

2010-03-01

Plant based repellent against mosquito borne diseases are used recently because synthetic repellents cause side effects like breathing problem, eye irritation, head ache, cough, etc. The use of natural products for dengue control would protect the environment, reduce dependence on expensive synthetic repellents and also generate local employment. Essential oil was isolated by steam distillation which was used against the bites of Aedes aegypti and duration of protection period was assessed. Skin-irritant potential test was also conducted on 25 healthy volunteers by using four-point scale. The increase in the concentrations of essential oil increased the mean protection time against the bites of Aedes aegypti. The lowest mean protection time was 180.0 min for 2.5% and highest time of 255.0 min for 10%. The mean score of zero for skin-irritant potential test for all the concentrations indicated that the essential oil did not cause irritation to human skin. Results indicated that the use of plant based repellent for the control of dengue fever would replace the currently used synthetic repellents which causes many side effects.

Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

PubMed Central

Meleine, Mathieu; Matricon, Julien

2014-01-01

According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical

Gender-related differences in irritable bowel syndrome: potential mechanisms of sex hormones.

PubMed

Meleine, Mathieu; Matricon, Julien

2014-06-14

According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical

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