Science.gov

Sample records for acute skin irritation

  1. Acute Toxicity and Skin Irritant Properties of Sulfolane

    PubMed Central

    Brown, V. K. H.; Ferrigan, L. W.; Stevenson, D. E.

    1966-01-01

    Sulfolane is a useful industrial solvent. The oral LD50 values were: rats, 1·7 to 2·7 g./kg.; mice, 1·9 to 2·5 g./kg., all deaths taking place within 24 hours. Rats showed no effects after 3·8 g./kg. had been applied to the skin. The compound did not irritate or sensitize the skins of guinea-pigs or rabbits and, undiluted, was almost without action on the eyes of rabbits. PMID:5926894

  2. 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.

  3. Effect of JP-8 jet fuel on molecular and histological parameters related to acute skin irritation.

    PubMed

    Kabbur, M B; Rogers, J V; Gunasekar, P G; Garrett, C M; Geiss, K T; Brinkley, W W; McDougal, J N

    2001-08-15

    Organic chemicals such as jet fuels and solvents can cause skin irritation after dermal exposure. The molecular responses to these chemicals resulting in acute irritation are not understood well enough to establish safe exposure limits. Male F-344 rats were dermally exposed to JP-8 jet fuel for 1 h using Hill Top Chambers. Whole skin samples were collected at 0, 1, 2, 4, and 6 h after the beginning of the exposures, homogenized, and analyzed for interleukin (IL)-1alpha and inducible nitric oxide synthase (iNOS) protein and nitrite levels. IL-1alpha levels (determined by ELISA) ranged from approximately 11 to 34% above the 0-h samples over the observed time period. At 1 and 2 h, significantly higher (p < 0.05) levels of IL-1alpha were detected when compared to the 0-h samples. Western blot analysis revealed significantly higher (p < 0.05) levels of iNOS at 4 and 6 h compared to 0-h samples. Increases in IL-1alpha and iNOS expression were also observed in the skin immunohistochemically. Nitrite concentrations in skin samples were measured to estimate nitric oxide production. Although nitrite concentrations in the skin increased approximately 6-27% above the 0-h samples over the observed time period, no significant changes in nitrite levels were detected. Pathological changes in the skin following JP-8 exposure were evaluated histologically. Increased numbers of granulocytes were observed infiltrating the skin at 2 h and were more prominent by 6 h. These data show that a 1-h exposure to JP-8 results in a local inflammatory response, which can be detected by changes in molecular and histological parameters. Copyright 2001 Academic Press.

  4. Comparative assessment of the acute skin irritation potential of detergent formulations using a novel human 4-h patch test method.

    PubMed

    Robinson, Michael K; Kruszewski, Francis H; Al-Atrash, Jenan; Blazka, Mark E; Gingell, Ralph; Heitfeld, Fred A; Mallon, David; Snyder, Neil K; Swanson, Judith E; Casterton, Phillip L

    2005-12-01

    Predictive skin irritation test methods, which do not require use of animals, are needed for the pre-market assessment of detergent formulations. The utility of a novel and ethical human acute skin irritation patch test method, originally developed for chemical skin irritation assessment, was evaluated. In this IRB-approved method, subjects were patched under occlusion for increasing periods of time up to 4h in duration. The total incidence of positive skin reactions for test products was compared to a positive control (20% aqueous sodium dodecyl sulfate [SDS]). Acutely irritating formulas were defined as those showing a significantly increased or equal incidence of positive responders compared with that of SDS. The time of exposure required for 50% of subjects to show a positive skin reaction (TR50 value) was calculated for each product and enabled test product comparisons within and between studies. Using this approach, 24 detergent formulations of various types were tested in seven individual studies. The skin irritation profiles were generally consistent within product types, which could be categorized as follows (by decreasing irritancy): mold/mildew removers (average TR50 = 0.37 h) > disinfectants/sanitizers (0.64 h) > fabric softener concentrate (1.09 h) = aluminum wash (1.20 h) > 20% SDS (1.81 h) > liquid laundry detergents (3.48 h) > liquid dish detergents (4.16 h) = liquid fabric softeners (4.56 h) = liquid hand soaps (4.58 h) = shampoos (5.40 h) = hard surface cleaners (6.34 h) > powder automatic dish detergents (>16 h) = powder laundry detergents (>16 h). In addition to formulation effects, some seasonal effects were noted; particularly greater winter-time reactivity to 20% SDS and the hard surface cleaner and liquid laundry formulations. These results demonstrate the utility of this patch test method for the comparative skin irritation assessment of these different product types.

  5. A strategy for skin irritation testing.

    PubMed

    Robinson, Michael K; Perkins, Mary A

    2002-03-01

    Skin irritation safety testing and risk assessment for new products, and the ingredients they contain, is a critical requirement before market introduction. In the past, much of this skin testing required the use of experimental animals. However, new current best approaches for skin corrosion and skin irritation testing and risk assessment are being defined, obviating the need for animal test methods. Several in vitro skin corrosion test methods have been endorsed after successful validation and are gaining acceptance by regulatory authorities. In vitro test methods for acute, cumulative (repeat exposure), and chronic (prolonged exposure) skin irritation are under development. Though not yet validated, many are being used successfully for testing and risk assessment purposes as documented through an expanding literature. Likewise, a novel acute irritation patch test in human subjects is providing a valid and ethical alternative to animal testing for prediction of chemical skin irritation potential. An array of other human test methods also have been developed and used for the prediction of cumulative/chronic skin irritation and the general skin compatibility of finished products. The development of instrumental methods (e.g., transepidermal water loss, capacitance, and so on) has provided the means for analyzing various biophysical properties of human skin and changes in these properties caused by exposure to irritants. However, these methods do not directly measure skin inflammation. A recently introduced skin surface tape sampling procedure has been shown to detect changes in skin surface cytokine recovery that correlate with inflammatory skin changes associated with chemical irritant exposures or existing dermatitis. It holds promise for more objective quantification of skin irritation events, including subclinical (sensory) irritation, in the future.

  6. Irritants and Skin Barrier Function.

    PubMed

    Angelova-Fischer, Irena

    2016-01-01

    The barrier response to irritant challenge involves complex biologic events and can be modulated by various environmental, exposure and host-related factors. Irritant damage to the epidermal barrier elicits a cascade of homeostatic or pathologic responses that could be investigated by both in vitro and in vivo methods providing different information at biochemical and functional level. The present chapter summarizes the changes in key barrier function parameters following irritant exposure with focus on experimental controlled in vivo human skin studies.

  7. 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

    and 6 days for 1,3-DNG and 1-MNG. WP caused depression, anorexia, and death in several days with enlarged yellow nutmeg livers. ^ 2,5-DNT was...several days. Animals that died were found to have large yellow nutmeg livers. Primary skin irritation and eye irritation tests were negative with a...amount of radioactivity is consistent with white phosphorus poisoning since enlarged nutmeg liver was observed in the acute oral toxicity study. The

  8. A prevalidation study on in vitro tests for acute skin irritation. results and evaluation by the Management Team.

    PubMed

    Fentem, J H; Briggs, D; Chesné, C; Elliott, G R; Harbell, J W; Heylings, J R; Portes, P; Roguet, R; van de Sandt, J J; Botham, P A

    2001-02-01

    A prevalidation study on in vitro tests for acute skin irritation was conducted during 1999 and 2000. The overall objective of validation in this area, of which this prevalidation study is an initial stage, is to identify tests capable of discriminating irritants (I) from non-irritants (NI), as defined according to European Union (EU) risk phrases ("R38"; no classification) and the harmonised OECD criteria ("Irritant"; no label). This prevalidation study specifically addressed aspects of: protocol refinement (phase I), protocol transfer (phase II), and protocol performance (phase III), in accordance with the prevalidation scheme defined by the European Centre for the Validation of Alternative Methods (ECVAM). The tests evaluated were: EpiDerm (phases I, II and III), EPISKIN (phases I, II and III), PREDISKIN (phases I and II, and additional protocol refinement), the non-perfused pig ear method (phases I and II, and additional protocol refinement), and the mouse skin integrity function test (SIFT; phases I and II). Modified, standardised test protocols and well-defined prediction models were available for each of the tests at the end of phase I. The results of phase I (intralaboratory reproducibility) were sufficiently promising for all of the tests to progress to phase II. Protocol transfer between the Lead Laboratory and Laboratory 2 was undertaken for all five tests during phase II, and additional refinements were made to the test protocols. For EpiDerm, EPISKIN and the SIFT, the intralaboratory and interlaboratory reproducibilities were acceptable; however, better standardisation of certain aspects of the test protocols was needed prior to commencing phase III. Neither PREDISKIN nor the pig ear test performed sufficiently well in phase II to progress to phase III. The PREDISKIN protocol was overly sensitive, resulting in the prediction of all the NI chemicals as I. The variability in the pig ear test results was too great, indicating that the test would show

  9. [Non-irritating skin protector].

    PubMed

    Gago Fornells, Manuel; García González, R Fernando; Gaztelu Valdés, Victoriana

    2002-05-01

    In this article, the authors describe the multiple uses a non irritating cutaneous protector has as an effective tool against the aggressions which peri-lesion skin and other at risk skins suffer when they are subject to constant and direct contact with secretions and liquids resulting from the use of dressings based on wet cures, or systems of continence related to ostomias, or in those patients who suffer mixed incontinence where diaper rash makes it difficult to maintain and care for the skin.

  10. 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.

  11. 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.

  12. The ECVAM international validation study on in vitro tests for acute skin irritation: selection of test chemicals.

    PubMed

    Eskes, Chantra; Cole, Thomas; Hoffmann, Sebastian; Worth, Andrew; Cockshott, Amanda; Gerner, Ingrid; Zuang, Valérie

    2007-12-01

    The ECVAM-funded skin irritation validation study (SIVS) was initiated in 2003, with the aim to evaluate whether the EpiDerm, EPISKIN and the SIFT alternative methods were able to reliably identify skin irritant and non-irritant chemicals, and could therefore be candidates for replacing the rabbit Draize test for skin irritation. The primary goal of the study was to evaluate the predictive capacity of the assays with regard to the EU classification system, which employs the risk phrases, "R38", for skin irritants, and "no label" for non-irritants. A secondary objective was the retrospective analysis of the data, to assess whether the in vitro tests would be able to discriminate between strong irritants (category 2), mild irritants (category 3) and non-irritants (no category), as defined by the OECD and United Nations proposal for a Globally Harmonised System (GHS) for the classification and labelling of dermal irritancy. A Chemicals Selection Sub-Committee (CSSC) was appointed to identify test chemicals to be used in the SIVS, for which existing, high quality in vivo data were available, with which to correlate the in vitro measurements. Since chemicals from the European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) database of reference chemicals for skin irritation/skin corrosion had been extensively used in preceding studies, the CSSC made use of novel sources for potential test chemicals. The first source of chemicals screened was the New Chemicals Database (NCD), which is the central archive within the EU notification scheme for 'new' commercial chemicals. Data registered in the NCD originate from standard assays, submitted in compliance with the legislation which regulates the marketing of industrial chemicals, and are subject to quality assurance by the competent authorities of the EU Member States. In addition, to obtain 'existing' chemicals which were readily available from major manufacturing and/or distribution sources, additional

  13. Skin irritation and sensitization: mechanisms and new approaches for risk assessment. 1. Skin irritation.

    PubMed

    Fluhr, J W; Darlenski, R; Angelova-Fischer, I; Tsankov, N; Basketter, D

    2008-01-01

    Cutaneous irritation presents a major health problem with serious social and occupational impact. The interaction between an irritant and the human skin depends on multiple factors: the intrinsic properties and the nature of the irritant itself, and specific individual- and environment-related variables. The main pathological mechanisms of irritancy include skin barrier disruption, induction of a cytokine cascade and involvement of the oxidative stress network; all of them resulting in a visible or subclinical inflammatory reaction. In vivo, different non-invasive parameters for the evaluation of skin irritation and irritant potential of compounds and their specific formulations have been introduced, such as epidermal barrier function, skin hydration, surface pH, lipid composition, skin colour and skin blood flow. The diverse physiological changes caused by irritating agents require implementation of a multiparametric approach in the evaluation of cutaneous irritancy.

  14. In vitro and human testing strategies for skin irritation.

    PubMed

    Robinson, M K; Osborne, R; Perkins, M A

    2000-01-01

    Prior to the manufacture, transport, and marketing of chemicals or products, it is critical to assess their potential for skin toxicity (corrosion or irritation), thereby protecting the worker and consumer from adverse skin effects due to intended or accidental skin exposure. Traditionally, animal testing procedures have provided the data needed to assess the more severe forms of skin toxicity, and current regulations may require animal test data before permission can be obtained to manufacture, transport, or market chemicals or the products that contain them. In recent years, the use of animals to assess skin safety has been opposed by some as inhumane and unnecessary. The conflicting needs of the industrial toxicologist to (1) protect human safety, (2) comply with regulations, and (3) reduce animal testing have led to major efforts to develop alternative, yet predictive, test methods. A variety of in vitro skin corrosion test methods have been developed and several have successfully passed initial international validation. These have included skin or epidermal equivalent assays that have been shown to distinguish corrosive from noncorrosive chemicals. These skin/epidermal equivalent assays have also been modified and used to assess skin irritation potential relative to existing human exposure test data. The data show a good correlation between in vitro assay data and different types of human skin irritation data for both chemicals and consumer products. The effort to eliminate animal tests has also led to the development of a novel human patch test for assessment of acute skin irritation potential. A case study shows the benefits of in vitro and human skin irritation tests compared to the animal tests they seek to replace, and strategies now exist to adequately assess human skin irritation potential without the need to rely on animal test methods.

  15. Follow-up to the ECVAM prevalidation study on in vitro tests for acute skin irritation. The European Centre for the Validation of Alternative Methods Skin Irritation Task Force report 2.

    PubMed

    Zuang, Valérie; Balls, Michael; Botham, Philip A; Coquette, Alain; Corsini, Emanuela; Curren, Rodger D; Elliott, Graham R; Fentem, Julia H; Heylings, Jon R; Liebsch, Manfred; Medina, Jesús; Roguet, Roland; van de Sandt, Johannes J M; Wiemann, Christianne; Worth, Andrew P

    2002-01-01

    The European Centre for the Validation of Alternative Methods (ECVAM) Skin Irritation Task Force was established in 1996, to review the status of the development and validation of alternative tests for skin irritation and corrosion, and to identify appropriate non-animal tests for predicting human skin irritation that were sufficiently well-developed to be prevalidated and validated by ECVAM. The EpiDerm method, based on a reconstituted human skin model, was proposed as being sufficiently well advanced to enter a prevalidation (PV) study. Based on a review of test protocols, prediction models (PMs), and data submitted by test developers on ten specified chemicals, with 20% sodium lauryl sulphate as a reference standard, the task force recommended the inclusion of four other tests: EPISKIN and PREDISKIN, based on reconstituted human epidermis or on human skin; the non-perfused pig-ear test, based on pig skin; and the skin integrity function test (SIFT), with ex vivo mouse skin. The prevalidation study on these methods was funded by ECVAM, and took place during 1999-2000. The outcome of the PV study was that none of the methods was ready to enter a formal validation study, and that the protocols and PMs of the methods had to be improved in order to increase their predictive abilities. Improved protocols and PMs for the EpiDerm and EPISKIN methods, the pig ear test, and the SIFT were presented at an extended Task Force meeting held in May 2001. It was agreed that, in the short term, the performance of the revised and harmonised EpiDerm and EPISKIN methods, as well as the modified SIFT, should be evaluated in a further study with a new set of 20 test chemicals. In addition, it was decided that the SIFT and the pig ear test would be compared to see if common endpoints (transepidermal water loss, methyl green-pyronine stain) could be identified.

  16. A comparison of the effect of certain inorganic salts on suppression acute skin irritation by human biometric assay: A randomized, double-blind clinical trial

    PubMed Central

    Fatemi, Sayedali; Jafarian-Dehkordi, Abbas; Hajhashemi, Valiollah; Asilian-Mahabadi, Ali; Nasr-Esfahani, Mohammad Hossein

    2016-01-01

    Background: Strontium, zinc, and potassium salts have been demonstrated to inhibit irritation and inflammation when applied topically. Particularly, strontium chloride (SC) and potassium nitrate (KN) are reported to reduce skin and tooth sensitivity. The aim of the present study was to compare the anti-irritant effects of four inorganic salts and assign the ingredient which can suppress skin irritation due to chemical or environmental exposure, more effectively. We compared the anti-inflammatory effects of SC, strontium nitrate (SN), KN, and zinc chloride (ZC). Materials and Methods: This double-blind trial was conducted on 32 healthy volunteers with sensitive skin. Irritation was induced by 24 h exposure with 1.0% sodium lauryl sulfate on arms. Treatments were applied by an ointment of SN, SC hexahydrate, KN, and ZC and their 1%, 3%, and 5% (w/v) concentrations were prepared. The dosage was twice daily for 6 days to the irritated areas. Skin reactions were evaluated instrumentally. Results: SC had a beneficial effect that was significant overall. All other treatments exert a protective effect in skin barrier function but not significantly. With the exception of ZC, all test substances improved skin hydration but the effect of SC was significant. In respect of colorimetric assessment, all treatments, excluding ZC, reduced erythema significantly compared with an untreated control 7 days after treatment start. There was no support for a dose-response effect. Conclusion: Analysis of the biometric measurements revealed that the strontium salts are best, not treating is worst, and there is little difference between the other treatments. Hence, the skin care products containing SC and SN may reduce the signs and symptoms of irritant contact dermatitis. PMID:28250779

  17. Cytotoxicity, acute oral toxicity, and skin irritation of 2-ethylhexyl-2,4,5-trimethoxycinnamate and di(2-ethylhexyl)-2,4,5-trimethoxybenzalmalonate.

    PubMed

    Monhaphol, Thitinun; Yibchok-Anun, Sirinthorn; Banlunara, Wijit; Wittayasuporn, Mayura; Palaga, Tanapat; Asawanonda, Pravit; Wanichweacharungruang, Supason

    2008-01-01

    Safety of two new ultraviolet (UV) filters, 2-ethylhexyl-2,4,5-trimethoxycinnamate (E8) and 2-ethylhexyl-2,4,5-trimethoxybenzalmalonate (B8), has been evaluated through the human melanoma cytotoxicity test and seven-day acute oral toxicity studies in rats. At 2.5 mg/mL, both compounds gave similar cell viability to the control. LD50 values for E8 and B8 are more than 5000 and 1000 mg/kg body weight, respectively. No significant difference in body weight and hematological parameters among the 0, 5, 50, 500, and 5000 mg/Kg E8-treated animals could be detected. Pathological examination of rat tissues collected at the end of the study period revealed no significant difference between the control and all E8-administered rats. There was no significant difference in all clinical blood chemistry parameters (aspartate aminotransferase, creatinine, blood urea nitrogen, and cholesterol), except alanine aminotransferase (ALT), between the control and the E8-treated animals. All ALT values were, however, in the normal range of SD rats. E8 showed negative results for the skin irritation study on human volunteers, using patch and photopatch tests. Excitation of respiratory signs of dypsnea in 10, 100, and 1000 mg/Kg B8-treated rats could be observed during 1-24 h. All groups were, however, normal during the second to the seventh day. Hematological parameters of the 0, 10, 100, and 1000 mg/Kg B8-treated animals showed no significant difference. Pathological examination revealed no significant difference between the control and all B8-administered rats. However, significant differences in some clinical blood chemistry parameters and body weights between the control and some B8-treated animals could be detected. All values, however, were in the normal ranges of the SD rats.

  18. [Irritant contact dermatitis. Part II. Evaluation evaluation of skin irritation potential of chemicals].

    PubMed

    Chomiczewska, Dorota; Kieć-Swierczyńska, Marta; Krecisz, Beata

    2009-01-01

    The evaluation of skin irritation potential of chemicals is essential to secure the safety of individuals exposed to several substances designed for industrial, pharmaceutical or cosmetic use. Until recently, preclinical safety assessment of chemicals was largely based on animal experiments. Ethical concerns and the limited value of animal models in evaluating human skin irritation potential resulted in the development of alternative in vitro methods, such as EpiDerm, EPISKIN or SkinEthic, to assess irritation, i.e. cell cultures and human epidermis models. International organizations like the European Centre for the Validation of Alternative Methods (ECVAM) promotes and monitors the development of nonanimal tests. Human patch tests and use tests also provide an opportunity to identify substances with significant skin irritation potential without recourse to the use of animals. These tests are useful to assess skin irritation potential of cosmetics and detergents.

  19. Cumulative skin irritation test of sanitary pads in sensitive skin and normal skin population.

    PubMed

    Farage, Miranda A; Maibach, Howard

    2007-01-01

    We performed a randomized, paired, double-blind trial involving 14 participants with self-declared normal skin and 15 participants with self-declared sensitive skin to test the cutaneous compatibility of materials of low irritation potential for skin irritation (sanitary pads) elicited by repetitive topical application. Two test products patches and two control substance patches were applied to the lateral aspect of the upper arm once daily under fully occlusive conditions for 4 days. The positive control patch was moistened with sodium lauryl sulphate (0.1% w/v) and the negative control patch was moistened with 0.9% sodium chloride, as were the two test material patches. The patches were removed, skin irritation (erythema) graded, and new patches applied after each 24-hour period. There was no significant difference in skin irritation from the test patches between the sensitive and normal skin groups. The two test patches and the negative control patch were significantly less irritating than the positive control in both test groups. Both test patches were comparable to the negative control patch in the normal and sensitive skin groups. The test materials produced similar degrees of skin irritation among both groups. Overall, there was no statistically significant difference in skin compatibility when the two feminine hygiene product test patches were worn by self-declared normal and sensitive skin groups.

  20. Human skin irritation studies of a lecithin microemulsion gel and of lecithin liposomes.

    PubMed

    Dreher, F; Walde, P; Luisi, P L; Elsner, P

    1996-01-01

    Soybean lecithin microemulsion gels offer promising features for the possible use as matrices in transdermal therapeutic systems. In order to assess the skin irritancy potential of the gel, acute and cumulative irriation tests were performed in human subjects in vivo using as comparison an unilamellar soybean lecithin liposome preparation and the solvent isopropyl palmitate (IPP). Acute irritation was tested in 151 volunteers in a 48-hour patch test, whereas cumulative irritation was assessed in a 21-day human repeated insult patch test in 20 volunteers. In the acute irritation test, discrete irritation (erythema only) developed with the gel in 2 subjects (1.3%), with the liposomes in 3 subjects (2.0%), and with IPP in 2 subjects (1.3%). For the assessment of cumulative irritation, the IT50 (irritation time of 50% of the test population) was calculated. IT50 was 13 days for the gel, 14 days for the liposomes and 17 days for IPP. This study shows a very low acute and a low cumulative irritancy potential for the soybean lecithin microemulsion gel making it a candidate matrix for transdermal therapeutic systems also under toxicological aspects.

  1. Cumulative irritation patch test of sanitary pads on sensitive skin.

    PubMed

    Farage, Miranda; Stadler, Angela

    2005-09-01

    Tools are needed to assess the effects of various products on sensitive skin. To investigate the cutaneous compatibility of various sanitary pads in people with self-declared sensitive skin. Eight subjects, who considered their skin to be sensitive and who reported adverse skin responses to everyday products or clothing, were patch tested on the arm with two, low-irritancy sanitary pads for four consecutive 24-hour periods. Test products differed only in their surface covering. Sodium lauryl sulfate solution (0.1% w/v) and physiological saline served as standard irritant and nonirritant controls, respectively. Skin irritation (erythema) was graded after each 24-hour period. No significant difference in skin erythema scores was observed between groups (scores on day 4: 1.06 +/- 0.11 vs. 1.25 +/- 0.13, on a five-point scale, P < 0.05). The temporal development of cumulative irritation associated with the pads was comparable to that observed with the nonirritant control (a plateau in maximal group scores) and distinct from that of the irritant control (continuously rising scores). Sanitary pads under investigation elicited negligible cumulative irritation in a four-day patch test on subjects with self-declared sensitive skin. The temporal pattern of cumulative response was consistent with the inherently low irritation potential of the products.

  2. The ECVAM international validation study on in vitro tests for acute skin irritation: report on the validity of the EPISKIN and EpiDerm assays and on the Skin Integrity Function Test.

    PubMed

    Spielmann, Horst; Hoffmann, Sebastian; Liebsch, Manfred; Botham, Phil; Fentem, Julia H; Eskes, Chantra; Roguet, Roland; Cotovio, José; Cole, Thomas; Worth, Andrew; Heylings, Jon; Jones, Penny; Robles, Catherine; Kandárová, Helena; Gamer, Armin; Remmele, Marina; Curren, Rodger; Raabe, Hans; Cockshott, Amanda; Gerner, Ingrid; Zuang, Valérie

    2007-12-01

    ECVAM sponsored a formal validation study on three in vitro tests for skin irritation, of which two employ reconstituted human epidermis models (EPISKIN, EpiDerm), and one, the skin integrity function test (SIFT), employs ex vivo mouse skin. The goal of the study was to assess whether the in vitro tests would correctly predict in vivo classifications according to the EU classification scheme, "R38" and "no label" (i.e. non-irritant). 58 chemicals (25 irritants and 33 non-irritants) were tested, having been selected to give broad coverage of physico-chemical properties, and an adequate distribution of irritancy scores derived from in vivo rabbit skin irritation tests. In Phase 1, 20 of these chemicals (9 irritants and 11 non-irritants) were tested with coded identities by a single lead laboratory for each of the methods, to confirm the suitability of the protocol improvements introduced after a prevalidation phase. When cell viability (evaluated by the MTT reduction test) was used as the endpoint, the predictive ability of both EpiDerm and EPISKIN was considered sufficient to justify their progression to Phase 2, while the predictive ability of the SIFT was judged to be inadequate. Since both the reconstituted skin models provided false predictions around the in vivo classification border (a rabbit Draize test score of 2), the release of a cytokine, interleukin-1alpha (IL-1alpha), was also determined. In Phase 2, each human skin model was tested in three laboratories, with 58 chemicals. The main endpoint measured for both EpiDerm and EPISKIN was cell viability. In samples from chemicals which gave MTT assay results above the threshold of 50% viability, IL-1alpha release was also measured, to determine whether the additional endpoint would improve the predictive ability of the tests. For EPISKIN, the sensitivity was 75% and the specificity was 81% (MTT assay only); with the combination of the MTT and IL-1alpha assays, the sensitivity increased to 91%, with a

  3. Assessment of skin and eye irritation of 14 products under the stepwise approach of the OECD.

    PubMed

    Mancebo, Axel; Hernández, Osvaldo; González, Yana; Aldana, Lizet; Carballo, Onelio

    2008-01-01

    The determination of acute eye and skin irritation is included in international regulatory requirements for the testing of chemicals, because of the possibility of exposure during the production, transport, marketing, and disposal of products. Although there have been some advances in the areas of refinement and reduction, no single battery of tests has emerged as being acceptable as a complete replacement for the conventional Draize rabbit eye and skin irritation tests. Currently, dermal irritation and ocular irritation are generally evaluated in a sequential manner in the context of tiered assessment strategies. In this work, we show how 14 products, mostly designed to be used in agriculture, were evaluated in the Center of Experimental Toxicology of the Center for the Production of Laboratory Animals (Centro Nacional para la Producción de Animales de Laboratorio; CENPALAB) in order to assess their acute dermal and ocular effects. The performed studies include the acute dermal toxicity test, the acute dermal irritation/corrosion test, the hen's egg test-chorioallantoic membrane (HET-CAM) method, and the acute eye irritation/corrosion test. In general, it could be concluded that of the 14 products assessed, none of them showed systemic effects, but local reactions mainly to the eyes. The most significant effects were apparently related to the effects of azadirachtin, an active principle of 2 tested neem derivatives.

  4. Evaluation of dermal and eye irritation and skin sensitization due to carbon nanotubes.

    PubMed

    Ema, Makoto; Matsuda, Akitaka; Kobayashi, Norihiro; Naya, Masato; Nakanishi, Junko

    2011-12-01

    The present paper summarizes the results of our studies on dermal and eye irritation and skin sensitization due to carbon nanotubes (CNTs), whose potential applications and uses are wide and varied, including CNT-enhanced plastics, electromagnetic interference/radio-frequency (EMI/RFI) shielding, antistatic material, flexible fibers and advanced polymers, medical and health applications, and scanning probe microscopy. Skin and eyes have the highest risk of exposure to nanomaterials, because deposition of nanomaterials to the surficial organs has the potential to be a major route of exposure during the manufacturing, use, and disposal of nanomaterials. Two products composed of single-walled carbon nanotubes (SWCNTs) and two products composed of multi-walled carbon nanotubes (MWCNTs) were tested regarding acute dermal and acute eye irritation using rabbits, and skin sensitization using guinea pigs. The concentrations of the CNTs in the substances were the maximum allowable for administration. The two products of SWCNTs and one of the products of MWCNTs were not irritants to the skin or eyes. The other product of MWCNTs caused very slight erythema at 24h, but not at 72h, after patch removal in the dermal irritation experiments and conjunctival redness and blood vessel hyperemia at 1h, but not at 24h, in eye irritation experiments. These findings showed that one product of MWCNTs was a very weak acute irritant to the skin and eyes. No products of SWCNTs and MWCNTs exhibited skin-sensitization effects. Our knowledge of the toxicological effects of CNTs is still limited. Further information is needed to clarify the potential for irritation and sensitization given the complex nature of CNTs. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Effect of topically applied lipids on surfactant-irritated skin.

    PubMed

    Lodén, M; Andersson, A C

    1996-02-01

    Moisturizers are used daily by many people to alleviate symptoms of dry skin. All of them contain lipids. It has been suggested that topically applied lipids may interfere with the structure and function of the permeability barrier. The influence of a single application of nine different lipids on normal skin and skin irritated by sodium lauryl sulphate (SLS) was studied in 21 healthy subjects. Parameters assessed were visible signs of irritation, and objectively measured cutaneous blood flow and transepidermal water loss (TEWL). The substances tested were hydrocortisone, petrolatum, fish oil, borage oil, sunflower seed oil, canola oil, shea butter, and fractions of unsaponifiable lipids from canola oil and shea butter. Water was included as a control. On normal skin, no significant differences in the effects of the test substances were found, whereas significant differences were observed when they were applied to SLS-irritated skin. The visible signs of SLS-induced irritation were significantly less pronounced after treatment with the sterol-enriched fraction from canola oil than after treatment with water. This fraction, and hydrocortisone, reduced cutaneous blood flow. Furthermore, application of hydrocortisone, canola oil, and its sterol-enriched fraction, resulted in significantly lower TEWL than with water. The other lipids had no effect on the degree of irritation. In conclusion, lipids commonly used in moisturizers may reduce skin reactions to irritants. Previous studies have shown that, in barrier perturbed skin, the synthesis of sterols is increased. The observed effects of canola oil and its fraction of unsaponifiable lipids on SLS-induced irritation suggest the possibility that they assisted the skin in supplying the damaged barrier with adequate lipids.

  6. Review of skin irritation/corrosion Hazards on the basis of human data: A regulatory perspective

    PubMed Central

    Jírova, Dagmar; Kandárová, Helena

    2012-01-01

    Regulatory classification of skin irritation has historically been based on rabbit data, however current toxicology processes are transitioning to in vitro alternatives. The in vitro assays have to provide sufficient level of sensitivity as well as specificity to be accepted as replacement methods for the existing in vivo assays. This is usually achieved by comparing the in vitro results to classifications obtained in animals. Significant drawback of this approach is that neither in vivo nor in vitro methods are calibrated against human hazard data and results obtained in these assays may not correspond to situation in human. The main objective of this review was to establish an extended database of substances classified according to their human hazard to serve for further development of alternative methods relevant to human health as well as resource for improved regulatory classification. The literature has been reviewed to assemble all the available information on the testing of substances in the human 4 h human patch test, which is the only standardized protocol in humans matching the exposure conditions of the regulatory accepted in vivo rabbit skin irritation test. A total of 81 substances tested according to the defined 4 h human patch test protocol were found and collated into a dataset together with their existing in vivo classifications published in the literature. While about 50% of the substances in the database are classified as irritating based on the rabbit skin test, on using the 4 h HPT test, less than 20% were identified as acutely irritant to human skin. Based on the presented data, it can be concluded that the rabbit skin irritation test largely over-predicts human responses for the evaluated chemicals. Correct classification of the acute skin irritation hazard will only be possible if newly developed in vitro toxicology methods will be calibrated to produce results relevant to man. PMID:23118595

  7. Effect of moisturizers on skin susceptibility to irritants.

    PubMed

    Held, E; Agner, T

    2001-05-01

    Moisturizers are used for the treatment of dry and irritated skin. The benefit of moisturizers when used on normal skin has recently been challenged, since an earlier study indicated that the increased hydration that follows long-term use of moisturizers on normal skin may facilitate penetration of irritants. The aim of the present study was to evaluate short-term use of 2 different moisturizers used on normal skin: cream A (high lipid content) and B (moderate/low lipid content). Nineteen healthy volunteers applied the moisturizers on the upper arm/forearm 3 times daily for 5 days, while the other upper arm/forearm served as symmetrical control. The day after moisturizer treatment was stopped the skin was challenged with a patch test of sodium lauryl sulphate. Skin reactions were evaluated by bioengineering measuring methods and clinical scoring. Skin response to sodium lauryl sulphate was increased on moisturizer-treated arms compared to controls for one of the moisturizer (cream A), while this was not statistically significant for the other moisturizer (cream B). Data confirm previous indications that some moisturizers when used on normal skin may increase skin susceptibility to irritants.

  8. Acute irritant reaction to an antiseptic bath emollient.

    PubMed

    Saw, N K; Hindmarsh, J R

    2005-02-01

    Antiseptic bath emollients are commonly prescribed for treatment of eczema and are generally safe for frequent application. Although acute irritant reactions are uncommon it is nevertheless recognised and could have significant morbidity. This case describes a young male patient who developed an acute irritant reaction localised to the external genitalia, mimicking Fournier's gangrene, after overnight application of Oilatum Plus antiseptic bath emollients.

  9. Acute irritant reaction to an antiseptic bath emollient

    PubMed Central

    Saw, N; Hindmarsh, J

    2005-01-01

    Antiseptic bath emollients are commonly prescribed for treatment of eczema and are generally safe for frequent application. Although acute irritant reactions are uncommon it is nevertheless recognised and could have significant morbidity. This case describes a young male patient who developed an acute irritant reaction localised to the external genitalia, mimicking Fournier's gangrene, after overnight application of Oilatum Plus antiseptic bath emollients. PMID:15701748

  10. ECVAM's activities in validating alternative tests for skin corrosion and irritation.

    PubMed

    Fentem, Julia H; Botham, Philip A

    2002-12-01

    ECVAM has funded and managed validation studies on in vitro tests for skin corrosion, resulting in the validities of four in vitro tests being endorsed by the ECVAM Scientific Advisory Committee: the rat skin transcutaneous electrical resistance (TER) assay, two tests based on the use of commercial reconstituted human skin equivalents, EPISKIN and EpiDerm, and another commercially-produced test, CORROSITEX. In the European Union (EU), a new test method on skin corrosion (B.40), incorporating the rat skin TER and human skin model assays, was included in Annex V of Directive 67/548/EEC in mid-2000, thereby making the use of in vitro alternatives for skin corrosion testing of chemicals mandatory in the EU. At the recommendation of its Skin Irritation Task Force, ECVAM has funded prevalidation studies on five in vitro tests for acute skin irritation: EpiDerm, EPISKIN, PREDISKIN, the pig-ear test, and the mouse-skin integrity function test (SIFT). However, none of the tests met the criteria (set by the Management Team for the studies) for inclusion in a large-scale formal validation study. Thus, to date, there are no validated in vitro tests for predicting the dermal irritancy of chemicals. Following further work on the EPISKIN, EpiDerm and SIFT test protocols and/or prediction models after the completion of the prevalidation studies, it appears that the modified tests could meet the performance criteria defined for progression to a validation study. This will now be assessed independently by the ECVAM Skin Irritation Task Force, with the objective of taking a decision before the end of 2002 on whether to conduct a formal validation study.

  11. Effect of different moisturizers on SLS-irritated human skin.

    PubMed

    Held, E; Lund, H; Agner, T

    2001-04-01

    Moisturizers are widely used to treat irritant contact dermatitis (ICD). Their use is, however, not well-documented and standardized models for testing skin care products are needed to acquire documentation of their efficacy. The present study was undertaken to evaluate the effect of 6 commonly-used moisturizers on the recovery of irritated human skin. No commercial interests were involved in the study. 36 healthy volunteers had patch tests with SLS 0.5% applied on their forearms/upper arms for 24 h. After irritation of the skin, all volunteers had a moisturizer applied on one forearm/upper arm, respectively, 3 x daily for the following 5 days. The other forearm/upper arm served as an untreated control. Each moisturizer was tested on 12 volunteers and each volunteer tested 2 moisturizers at the same time. Evaluation was done on days 1, 3 and 8 by transepidermal water loss, electrical capacitance, laser Doppler flowmetry, DermaSpectrometry and clinical scoring. All 6 moisturizers were found to accelerate regeneration of the skin barrier function when compared to irritated non-treated skin. The most lipid-rich moisturizers improved barrier restoration more rapidly than the less lipid-rich moisturizers. We suggest this experimental model for further moisturizer efficacy testing.

  12. In Vitro Comparative Skin Irritation Induced by Nano and Non-Nano Zinc Oxide

    PubMed Central

    Vinardell, Maria Pilar; Llanas, Hector; Marics, Laura; Mitjans, Montserrat

    2017-01-01

    This study was designed to determine whether nano-sized ZnO has the potential to cause acute cutaneous irritation using cultured HaCaT keratinocytes and a human skin equivalent as in vitro models, compared to non-nanomaterials. Commercial nano ZnO with different sizes (50 nm and 100 nm) was characterized by dynamic light scattering (DLS) and microscopy (SEM) in different media. Nano ZnO reduced the cell viability of HaCaT in a dose-dependent and time-dependent manner, in a similar way to macro ZnO. However, the 3D-epidermis model revealed no irritation at 1 mg/mL after 24 h of exposure. In conclusion, nano-sized ZnO does not irritate skin, in a similar manner to non-nano ZnO. PMID:28336890

  13. In Vitro Comparative Skin Irritation Induced by Nano and Non-Nano Zinc Oxide.

    PubMed

    Vinardell, Maria Pilar; Llanas, Hector; Marics, Laura; Mitjans, Montserrat

    2017-03-04

    This study was designed to determine whether nano-sized ZnO has the potential to cause acute cutaneous irritation using cultured HaCaT keratinocytes and a human skin equivalent as in vitro models, compared to non-nanomaterials. Commercial nano ZnO with different sizes (50 nm and 100 nm) was characterized by dynamic light scattering (DLS) and microscopy (SEM) in different media. Nano ZnO reduced the cell viability of HaCaT in a dose-dependent and time-dependent manner, in a similar way to macro ZnO. However, the 3D-epidermis model revealed no irritation at 1 mg/mL after 24 h of exposure. In conclusion, nano-sized ZnO does not irritate skin, in a similar manner to non-nano ZnO.

  14. 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 tmin 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, tmin 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.

  15. Dermal and ocular irritation and skin sensitization studies of fullerene C60 nanoparticles.

    PubMed

    Ema, Makoto; Matsuda, Akitaka; Kobayashi, Norihiro; Naya, Masato; Nakanishi, Junko

    2013-06-01

    Widespread production and use of nanomaterials have caused the release of increasing amounts of nanomaterials into the environment. The introduction of novel materials into industry requires safety evaluations as well as an understanding of the impact of the nanomaterials on human health, because the unique properties and size of nanomaterials may also result in unique health risks. Skin and eyes have the highest risk of exposure to nanomaterials, because deposition to the superficial organs has the potential to be a major route of exposure during the manufacturing, use, and disposal of nanomaterials. However, information on the dermal and eye irritation and sensitization of fullerene C(60) nanoparticles is still lacking. This study was performed to examine the potential irritating and sensitizing effects of fullerenes on the skin and eyes. The dermal and eye irritation study was performed using rabbits according to the Organisation for Economic Co-operation and Development (OECD) Guidelines 404 and 405, respectively. The skin sensitization study was carried out in accordance to the OECD Guideline 406 using guinea pigs. The concentrations of the fullerenes in the test substances were the maximum allowable for administration. Fullerenes were applied at 50 mg in dermal irritation, 40 mg in skin sensitization, and 100 mg in eye irritation studies. No dermal responses, including erythema/eschar or edema, were found in rabbits treated with fullerenes. No rabbits exhibited corneal opacity, abnormality of the iris, or chemosis eye at any time point after the application of fullerenes. Fullerenes caused conjunctival redness and blood vessel hyperemia at 1 h, but not at 24 h. No erythema or edema was observed after the challenge with fullerenes in the fullerene-treated guinea pigs. Reversible minimal potential for acute irritation of the eyes was induced by fullerenes, but neither irritation nor sensitization was caused on the skin. Although the present study provided

  16. The effect of damaged skin barrier induced by subclinical irritation on the sequential irritant contact dermatitis.

    PubMed

    Yan-yu, Wu; Xue-min, Wang; Yi-Mei, Tan; Ying, Cheng; Na, Liu

    2011-12-01

    Skin damage caused by a single specific stimulus has been extensively studied. However, many additional mild skin irritants are experienced every day before obvious irritant contact dermatitis (ICD) appears. The effect that these previously experienced mild irritations have on the incidence and severity of sequential ICD remains undefined. The purpose of this work was to explore whether the effects of skin barrier damage induced by either the open patch test with 1% sodium lauryl sulfate (SLS), tape stripping test (TAP) (10×), or irradiation with 0.75 median erythemal dose UVB (MED) will affect the severity of sequential irritant dermatitis induced by a 0.5% SLS occlusive patch test (PT). Nine treatments were applied to nine different locations of the ventral forearm of each subject at random. The nine treatment types were as follows: open patch test with 1% SLS; 10× TAP; UVB irradiation with 0.75 MED; open patch test with 1% SLS + PT with 0.5% SLS (SLSPT); 10× TAP + PT with 0.5% SLS (TAPPT); UVB irradiation with 0.75 MED + PT with 0.5% SLS (UVPT); PT with distilled water (DISPT); PT with 0.5% SLS (PT); and the CONTROL (no treatment). After 5 days of subclinical irritation, the PT was applied on day 6. Transepidermal water loss (TEWL), capacitance (CAP), and skin color (a*) were measured at baseline and on days 6, 7, and 8. After the PT, indices of irritancy of PT, UVPT, SLSPT, and TAPPT were 60, 80, 87 and 100%, respectively. The index of irritancy of TAPPT and SLSPT were significantly higher than that of PT (p < 0.05). Clinical scores of SLSPT and TAPPT were also significantly higher than PT (p < 0.05). After 5 days of irritation, TEWL of SLS, TAP, SLSPT, and TAPPT were increased significantly compared to that of baseline. After the PT, D-value of TEWL between day 8 and day 6 ((≥6-8)TEWL) of SLSPT and TAPPT were greater than that of PT, and D-value of TEWL between day 8 and day 7 ((≥7-8)TEWL) of SLSPT and TAPPT were less than that of PT values. After the

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

    PubMed

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

    2010-02-01

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

  18. Laundry detergents and skin irritancy--a comprehensive review.

    PubMed

    Crawford, Charles; Zirwas, Matthew J

    2014-01-01

    Surface-active agents (surfactants) form the foundation of an effective detergent formulation. As such, surfactants are a major component of laundry detergents. Depending on multiple factors, the amount of residual detergent surfactants in clothing after washing varies but may be sufficient to elicit skin irritation in susceptible individuals and in patients with existing dermatologic disorders. The goal of this review is to examine the relationship between surfactants commonly used in laundry detergent formulations and their potential for skin irritancy. In this context, the role of surfactants in achieving broad-spectrum cleaning performance in laundry is discussed, and currently available methodologies to evaluate and measure the effect of surfactant exposure on the skin are reviewed.

  19. Effects of disinfectants and detergents on skin irritation.

    PubMed

    Slotosch, Caroline M; Kampf, Günter; Löffler, Harald

    2007-10-01

    We investigated the biological response of regular human skin to alcohol-based disinfectants and detergents in a repetitive test design. Using non-invasive diagnostic tools such as transepidermal water loss, laser-Doppler flowmetry and corneometry, we quantified the irritative effects of a propanol-based hand disinfectant (Sterillium), its propanol mixture (2-propanol 45% w/w and 1-propanol 30% w/w), sodium lauryl sulfate (SLS) 0.5% and distilled water. The substances were applied in a 2-D patch test in a repetitive occlusive test design to the back. Additionally, we performed a wash test on the forearms that was supposed to mimic the skin affection in the normal daily routine of health care workers. In this controlled half-side test design, we included the single application of the hand rub, SLS 0.5% and water as well as a tandem application of the same substances. Patch test and wash test showed similar results. The alcohol-based test preparations showed minimal irritation rather comparable to the application of water. However, the detergent SLS produced stronger barrier disruption, erythema and dryness than the alcohol-based preparations. There was no additional irritation at the combined use of SLS and disinfectants. By contrary, there was even a decrease in barrier disruption and erythema induced by the tandem application of SLS followed by alcohol-based disinfection compared with the use of SLS alone. These findings show a less irritant effect of alcohol-based disinfectants on the skin than detergents. Our study shows that there is no summation of irritating effects of a common detergent and propanol and that the combination of washing and disinfection has a rather protective aspect compared with washing alone.

  20. 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

  1. Comparison of objective and sensory skin irritations of several cosmetic preservatives.

    PubMed

    Lee, Eunyoung; An, Susun; Choi, Dongwon; Moon, Seongjoon; Chang, Ihseop

    2007-03-01

    There are many cosmetic ingredients, such as preservatives and fragrances, known to elicit adverse effects. The aim of this study was to investigate the side-effects of cosmetic preservatives, by evaluating objective and subjective skin irritation. The method comprised of 2 parts. In part 1, we tried to compare 24-hr patch test results with the sensory irritation potential of several preservatives. In part 2, skin cumulative irritation test for 21 days and sensory irritation test were performed to compare various combinations of preservatives in 4 types of formulations. Our data showed that methylparaben, ethylparaben, propylparaben, butylparaben, phenoxyethanol (PE) and chlorphenesin (CPN) have similar objective skin irritation potential at the minimal inhibitory concentration of each preservative, but CPN has higher potential than other preservatives in subjective irritation. Sensory irritation of preservatives changed according to formulation type, and PE combined with CPN highly increased irritation. There was correlation between antimicrobial activity and skin objective irritation but not sensory irritation. Influence on skin sensory irritation varies with the combination of preservatives. Therefore, for the development of new preservatives and cosmetics, it is important to evaluate skin sensory irritation of preservatives used in cosmetic products according to the type of formulations.

  2. Irritation and allergy patch test analysis of topical treatments commonly used in wound care: evaluation on normal and compromised skin.

    PubMed

    Trookman, Nathan S; Rizer, Ronald L; Weber, Teresa

    2011-03-01

    Topical agents indicated for the treatment of superficial wounds have the potential to cause irritation or allergic contact dermatitis, particularly when applied to an impaired skin barrier. We sought to compare the irritancy potential of 5 topical wound care products commonly used in dermatologic practice on normal and compromised skin. Agents tested included Aquaphor Healing Ointment (AHO) (Beiersdorf Inc, Wilton, CT); bacitracin; Biafine Topical Emulsion (BTE) (OrthoNeutrogena, Los Angeles, CA); Neosporin (Poly/Bac/Neo) (Johnson & Johnson, New Brunswick, NJ); and Polysporin (Poly/Bac) (Johnson & Johnson). Study 1 assessed cumulative irritation using a modified human repeat insult patch test on normal back skin with an induction phase (test materials applied under occlusive patch 9 times at 48- to 72-hour intervals) and a challenge phase (test materials applied to original and naïve sites for 48 hours, 12-24 days postinduction). Irritation was graded for erythema and type IV allergy skin responses. Study 2 assessed the acute irritation potential of agents on tape-stripped ("wounded") back skin. Test sites were graded for erythema, transepidermal water loss, and skin color (Chroma Meter a∗) (Minolta, Osaka, Japan) at 48 and 72 hours poststripping. In study 1, cumulative irritation testing in 108 subjects classified AHO, bacitracin, Poly/Bac/Neo, and Poly/Bac as "mild," and BTE as "probably mild." In study 2 at 72 hours, mean clinical grading scores were significantly higher for BTE and Poly/Bac/Neo than AHO. Transepidermal water loss and colorimeter a∗ values were significantly lower for AHO and bacitracin compared with BTE. No allergic contact dermatitis was seen in either study. Patch test studies demonstrated that BTE showed the greatest irritancy potential in both normal and compromised skin whereas AHO showed the least. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  3. Dicationic alkylammonium bromide gemini surfactants. Membrane perturbation and skin irritation.

    PubMed

    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.

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

  6. Correlation study in skin and eye irritation between rabbits and humans based on published literatures.

    PubMed

    Ishii, Satoko; Ishii, Kaori; Nakadate, Masahiro; Yamasaki, Kanji

    2013-05-01

    The purpose of this study was to investigate the correlations in skin and eye irritations between rabbits and humans using published international databases. We selected 60 and 56 compounds for skin and eye irritation, respectively. When the reactions were divided into irritation-negative or irritation-positive, including corrosion, similar reactions between rabbits and humans were detected for 53 compounds in skin irritation and 54 compounds in eye irritation, showing rates of agreement in skin and eye as 88% and 96%, respectively. These findings revealed that correlation in skin and eye irritations between rabbits and humans were high. However, corrosion was observed in rabbit skin treated with 14 compounds, 4 of which showed similar changes in humans, and in rabbit eyes treated with 9 compounds, 1 of which revealed similar changes in humans. These findings indicated that the incidence of corrosion was higher in rabbits than in humans. Our results showed that the data on rabbit irritations in the skin and eye were useful for identifying risk of irritation in human. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Thymic stromal lymphopoietin induction by skin irritation is independent of tumour necrosis factor-α, but supported by interleukin-1.

    PubMed

    Kumari, V; Babina, M; Hazzan, T; Worm, M

    2015-04-01

    Thymic stromal lymphopoietin (TSLP) is an extensively studied cytokine linked to the pathogenesis of allergic diseases, but the inherent activities behind TSLP expression are not well defined. To explore the conditions favourable to TSLP induction outside of a typically allergic set-up and determine the associated mechanisms, and to assess whether TSLP is similarly controlled in murine and human skin. A combination of primary keratinocytes, skin explants/epidermal sheets and in vivo strategies was employed. The skin of wild-type and tumour necrosis factor knockout (TNF-/-) mice was subjected to acute irritation. Cells and specimens were stimulated with a range of TSLP inducers in the presence or absence of neutralizing antibodies. TSLP was quantitated by quantitative reverse-transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry. In addition to cytokines, skin irritation brought about by various causes (e.g. shaving, scratching and chemical perturbation) elicited uniformly high-level production of TSLP, which entered the circulatory system. Despite the potency of TNF-α as an in vitro TSLP inducer, the use of TNF-/- mice revealed that this mechanism was completely independent of endogenous TNF-α. Conversely, irritation-elicited TSLP depended on interleukin (IL)-1, which had a more pronounced influence in human skin than in murine skin. Murine and human skin differed considerably regarding TSLP regulation. Thymic stromal lymphopoietin is a general responder to disrupted skin homeostasis and may have a role in triggering the alarm system of the skin. TSLP induction is rapid, transient and driven by a mechanism that does not involve TNF-α, but partially relies on the evolutionarily ancient IL-1 system. The irritated skin secretes TSLP into the circulatory system. TSLP regulation varies between species. © 2014 British Association of Dermatologists.

  8. Formulation optimization, skin irritation, and efficacy characterization of a novel skin-lightening agent.

    PubMed

    Jain, Piyush; Sonti, Sujatha; Garruto, John; Mehta, Rahul; Banga, Ajay K

    2012-06-01

    Skin-lightening preparations are used by people all over the world for a diverse range of dermatologic indications. The gold standard treatment for skin lightening is with hydroquinone but has been controversial because of the presence of several side effects. Therefore, there has been a constant search for developing new treatment alternatives. Furthermore, the new amendments and bans on animal testing by ECVAM have made the three-dimensional models like EpiDerm(™) and MelanoDerm(™) increasingly popular. This work aims at the formulation development for a new skin-lightening agent, SMA-012, followed by testing for skin irritation and efficacy. Formulation parameters such as concentration of SMA-012, amount of ethanol, effect of permeation enhancers and pH were first optimized using Franz cell experiments. Tape stripping and underlying skin assays were performed to analyze the amounts of SMA-012 in different layers of skin. The irritation potential and efficacy of the screened formulation were evaluated using Epiderm(™) and Melanoderm(™) models. Skin permeation experiments suggested that concentrations of 0.1% SMA-012, 35% ethanol, and pH of 8.5 to be the best formulation characteristics. This particular formulation was found to be nonirritant for short-term exposure, when tested in Epiderm(™) model and also significantly effective in decreasing the amount of melanin in pigmented skin equivalent models. SMA-012 shows a good promise as a skin-lightening agent for cosmetic and therapeutic applications. Additionally, our study demonstrates the application of skin equivalent models as alternatives to animal testing in studying the regulation of skin pigmentation. © 2012 Wiley Periodicals, Inc.

  9. From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide.

    PubMed

    Brodsky, Berta; Erlanger-Rosengarten, Avigail; Proscura, Elena; Shapira, Elena; Wormser, Uri

    2008-06-15

    The primary purpose of the present study was to investigate the mechanism of the counter-irritating activity of topical iodine against skin lesions induced by chemical and thermal stimuli. The hypothesis that iodine exerts its activity by inducing an endogenous anti-inflammatory factor was confirmed by exposing guinea pig skin to heat stimulus followed by topical iodine treatment and skin extraction. Injection of the extract into naïve guinea pigs reduced heat-induced irritation by 69%. The protective factor, identified as a new nonapeptide (histone H2A 36-44, H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH), caused reduction of 40% in irritation score in heat-exposed guinea pigs. The murine analog (H-Lys-Gly-His-Tyr-Ala-Glu-Arg-Val-Gly-OH, termed IIIM1) reduced sulfur mustard (SM)-induced ear swelling at a dose-dependent bell-shape manner reaching peak activity of 1 mg/kg. Cultured keratinocytes transfected with the peptide were more resistant towards SM than the control cells. The peptide suppressed oxidative burst in activated neutrophils in a concentration-dependent manner. In addition, the peptide reduced glucose oxidase-induced skin edema in mice at a dose-dependent bell-shape manner. Apart from thermal and chemical-induced skin irritation this novel peptide might be of potential use in chronic dermal disorders such as psoriasis and pemphigus as well as non-dermal inflammatory diseases like multiple sclerosis, arthritis and colitis.

  10. From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide

    SciTech Connect

    Brodsky, Berta; Erlanger-Rosengarten, Avigail; Proscura, Elena; Shapira, Elena; Wormser, Uri

    2008-06-15

    The primary purpose of the present study was to investigate the mechanism of the counter-irritating activity of topical iodine against skin lesions induced by chemical and thermal stimuli. The hypothesis that iodine exerts its activity by inducing an endogenous anti-inflammatory factor was confirmed by exposing guinea pig skin to heat stimulus followed by topical iodine treatment and skin extraction. Injection of the extract into naive guinea pigs reduced heat-induced irritation by 69%. The protective factor, identified as a new nonapeptide (histone H2A 36-44, H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH), caused reduction of 40% in irritation score in heat-exposed guinea pigs. The murine analog (H-Lys-Gly-His-Tyr-Ala-Glu-Arg-Val-Gly-OH, termed IIIM1) reduced sulfur mustard (SM)-induced ear swelling at a dose-dependent bell-shape manner reaching peak activity of 1 mg/kg. Cultured keratinocytes transfected with the peptide were more resistant towards SM than the control cells. The peptide suppressed oxidative burst in activated neutrophils in a concentration-dependent manner. In addition, the peptide reduced glucose oxidase-induced skin edema in mice at a dose-dependent bell-shape manner. Apart from thermal and chemical-induced skin irritation this novel peptide might be of potential use in chronic dermal disorders such as psoriasis and pemphigus as well as non-dermal inflammatory diseases like multiple sclerosis, arthritis and colitis.

  11. Development of a standardized testing procedure for assessing the irritation potential of occupational skin cleansers.

    PubMed

    Elsner, Peter; Seyfarth, Florian; Antonov, Dimitar; John, Swen Malte; Diepgen, Thomas; Schliemann, Sibylle

    2014-03-01

    Frequent skin cleaning fulfils the definition of occupational 'wet work'. Standardized methods are required to assess the irritation potential of workplace cleansers. To develop a standardized procedure for testing the irritation potential of occupational skin cleansers. In this single-blind, single-centre trial in 25 healthy volunteers, the irritation potential of five generic reference cleansers was tested by three-times-daily washing with an automated skin cleaning device for 4 days, and quantification of cumulative skin barrier damage was performed by visual scoring, chromametry, transepidermal water loss TEWL, and corneometry. For two cleansers, reproducibility of the irritancy assessment was assessed. Furthermore, the irritation induced by four commercial workplace skin cleansers was studied. Whereas no significant changes were observed for any of the tested cleansers by either visual scoring or chromametry, significant increases in TEWL and significant decreases in stratum corneum hydration were found for all cleansers. Cleansers differed significantly in their irritation potential. On retesting of two cleansers, the first results were confirmed. Among the four commercial cleansers, one that was claimed to be mild was found to be disproportionally irritant. The presented model for testing cleansing preparations allows a highly controlled, practically relevant and reproducible irritancy assessment of occupational skin cleansers. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. In vitro skin irritation testing: Improving the sensitivity of the EpiDerm skin irritation test protocol.

    PubMed

    Kandárová, Helena; Hayden, Patrick; Klausner, Mitch; Kubilus, Joseph; Kearney, Paul; Sheasgreen, John

    2009-12-01

    A skin irritation test (SIT) utilising a common protocol for two in vitro reconstructed human epidermal (RhE) models, EPISKIN and EpiDerm, was developed, optimised and evaluated as a replacement for the in vivo rabbit skin irritation test in an ECVAM-sponsored validation study. In 2007, both RhE models were recognised by an independent peer-review panel and the ECVAM Scientific Advisory Committee (ESAC) as validated for use with the common SIT protocol. The EPISKIN SIT was endorsed as a full replacement of the in vivo rabbit test. Since the EpiDerm SIT proved to be less sensitive than the in vivo test and the EPISKIN SIT, the test was recognised as a validated component of a tiered testing strategy, in which positive results are accepted and negative results require further confirmation. The ESAC, in its April 2007 statement, also recommended increasing the sensitivity of the EpiDerm SIT, in order to gain the full acceptance. Analysis of the EpiDerm and EPISKIN data from the ECVAM validation study indicated that the lower sensitivity of the EpiDerm SIT might be linked to the more robust barrier properties of the EpiDerm model. This hypothesis was also in line with results published previously. To overcome the relatively low sensitivity of the EpiDerm protocol as a hindrance to full regulatory acceptance, a modification of exposure conditions was introduced into the protocol to achieve better agreement with the in vivo rabbit data. In the Modified EpiDerm SIT protocol, the test chemical exposure time was increased from 15 minutes to 60 minutes. In addition, part of the exposure was performed at 37 degrees C. When the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) viability assay endpoint was used for classification, a significant increase of sensitivity was obtained (86.1%), whilst maintaining the high specificity of the method (76.3%). With the change to the EU classification system, which now uses higher cut-off for the classification of

  13. Measurement of oedema in irritant-exposed skin by a dielectric technique.

    PubMed

    Miettinen, M; Mönkkönen, J; Lahtinen, M-R; Nuutinen, J; Lahtinen, T

    2006-11-01

    Easily applicable water-specific instruments measuring local oedema in skin are not available. The aim of this study is to demonstrate quantitative assessment of skin oedema with the dielectric technique by measuring increase of skin water content related to sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Irritant skin reaction and resulting oedema were induced by an irritant patch test on volar forearms in 12 healthy volunteers with the application of 1% SLS for 6 h. After occlusion the volunteers were divided into two groups: the patch test site of group I (six volunteers) received no treatment other than a base cream for the skin reaction, while for group II (six volunteers) a strong corticosteroid (clobetasol propionate) was applied on the irritant skin. During a follow-up of 72 h, erythema was scored visually, and irritant-induced oedema was measured with a novel water-specific instrument MoistureMeter-D. In the untreated irritant skin, a maximum increase of 45% in skin water content was found at 10 h postocclusion and water content was still elevated at 72 h. With these persons, the degree of oedema agreed well with the ultrasound-measured skin thickness (P=0.053). In the corticosteroid-treated skin, an increase of 8% in water content was measured during 72 h but there was no correlation between oedema and skin thickness. There was no correlation between erythema and oedema in untreated or corticosteroid-treated skin. The new instrument can easily be applied for noninvasive quantitative evaluation of local oedema and fluid retention in irritant-exposed skin.

  14. 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.

  15. 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

    2017-06-15

    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.

  16. Non-animal testing strategies for assessment of the skin corrosion and skin irritation potential of ingredients and finished products.

    PubMed

    Robinson, M K; Cohen, C; de Fraissinette, A de Brugerolle; Ponec, M; Whittle, E; Fentem, J H

    2002-05-01

    The dermatotoxicologist today is faced with a dilemma. Protection of workers and consumers from skin toxicities (irritation and allergy) associated with exposure to products, and the ingredients they contain, requires toxicological skin testing prior to manufacture, transport, or marketing. Testing for skin corrosion or irritation has traditionally been conducted in animals, particularly in rabbits via the long established Draize test method. However, this procedure, among others, has been subject to criticism, both for its limited predictive capacity for human toxicity, as well as for its use of animals. In fact, legislation is pending in the European Union which would ban the sale of cosmetic products, the ingredients of which have been tested in animals. These considerations, and advancements in both in vitro skin biology and clinical testing, have helped drive an intensive effort among skin scientists to develop alternative test methods based either on in vitro test systems (e.g. using rat, pig or human skin ex vivo, or reconstructed human skin models) or ethical clinical approaches (human volunteer studies). Tools are now in place today to enable a thorough skin corrosion and irritation assessment of new ingredients and products without the need to test in animals. Herein, we describe general testing strategies and new test methods for the assessment of skin corrosion and irritation. The methods described, and utilized within industry today, provide a framework for the practicing toxicologist to support new product development initiatives through the use of reliable skin safety testing and risk assessment tools and strategies.

  17. In vitro skin irritation: facts and future. State of the art review of mechanisms and models.

    PubMed

    Welss, Thomas; Basketter, David A; Schröder, Klaus R

    2004-06-01

    The skin is the main target tissue for exogenous noxes, protecting us from harmful environmental hazards, UV-irradiation and endogenous water loss. It is composed of three layers, whereas the outermost epidermis is a squamous epithelium that mainly consists of keratinocytes. These cells execute a terminal differentiation, which finally results in the assembly of the stratum corneum. This layer, consisting of cornified keratinocytes, is an effective barrier against a vast number of substances. Apart of this, keratinocytes play crucial roles in the immune surveillance and the initiation, modulation and regulation of inflammation in the epidermis. Regarding cutaneous inflammatory reactions, skin irritation is one of the most common adverse effect in humans. For reasons of human safety assessment new chemicals are still evaluated for irritant potentials by application to animals followed by visible changes such as erythema and oedema. Testing for skin irritation in animals potentially cause them pain and discomfort. Furthermore, the results are not always predictive for those found in humans. In order to replace animal testing and to improve the prediction of irritants, the cosmetic and toiletry industry, in Europe represented by Colipa, develops and uses several alternative in vitro test systems. In this respect, the use of in vitro reconstructed organotypic skin equivalents are mostly favored, because of their increasingly close resemblance to human skin. Due to ethical and scientific questions and on account of the 7th amendment of the European Council Directive 76/768/EEC, the authors see the requirement to drive the development of alternative tests for irritants. Therefore, this article centres on cosmetic ingredients and provides the readership an overview of the state of art of cellular mechanisms of skin irritation and summarizes the results of the commonly used skin equivalents to evaluate irritation in vitro.

  18. Irritancy of low concentrations of soap and synthetic detergents as measured by skin water loss.

    PubMed

    Hassing, J H; Nater, J P; Bleumink, E

    1982-05-01

    The irritancy of low concentrations of commercially available soaps and detergents (surfactants) in bar form was determined by means of measurements of water loss of the skin. The percentage of increase of vapor (water) loss after application of the soap solutions was taken as a measure of skin irritancy. The tests were performed in 19 human volunteers with 1% solutions of Sporex, Devela, Lux, Lactacyd and Aveenoderm. Devela and Lactacyd were found to provoke marked effects, Lux was less harmful whereas Sporex and Aveenoderm did not lead to a considerable increase of skin vapor loss. Longitudinal studies showed that the irritant properties of soap solutions are additive. The results suggest that the influences of the pH of a soap solution on the skin-damaging effort is less important than assumed thus far.

  19. Hydrophilic Dogwood Extracts as Materials for Reducing the Skin Irritation Potential of Body Wash Cosmetics.

    PubMed

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

    2017-02-19

    A significant problem related to the use of surfactants in body wash cosmetics is their propensity to trigger skin irritations. Only scarce literature exists on the effect of plant extracts on the skin irritation potential. The present study is an attempt to determine the effect of hydrophilic dogwood extracts on the irritant potential of body wash gels. Extractants used in the study were water and mixtures of water with glycerine, water with trimethylglycine (betaine), and water with plant-derived glycol (propanediol). The basic biochemical properties, i.e., the ability to neutralize free radicals, and the content of polyphenols, anthocyanins and flavonoids, were determined. An attempt was undertaken to analyze the impact of the extract added to natural body wash gel formulations on product properties. The skin irritation potential was assessed by determining the zein number and the increase in the pH level of the bovine serum albumin (BSA) solution. The viscosity and foaming ability of the resulting products were evaluated. The studies revealed that an addition of dogwood extract contributes to an improvement in the properties of body wash gels and significantly increases the safety of product use through reducing the skin irritation effect.

  20. Rat epidermal keratinocyte organotypic culture (ROC) as a model for chemically induced skin irritation testing

    SciTech Connect

    Pappinen, Sari . E-mail: sari.pappinen@uku.fi; Pasonen-Seppaenen, Sanna; Suhonen, Marjukka; Tammi, Raija; Urtti, Arto

    2005-11-01

    The potential of rat epidermal keratinocyte (REK) organotypic culture (ROC) with proper stratum corneum barrier as a model for screening skin irritants was evaluated. The test chemicals were selected from ECETOC database (1995) and the observed in vitro irritation potential was compared to ECETOC in vivo primary irritation index (PII), to EU risk phrases, and to the harmonized OECD criteria. Chemicals were applied onto the stratum corneum surface of ROC for 30 min and samples were taken from the underlying medium at 4 and 8 h after exposure. Cell membrane integrity (determined by LDH assay) and pro-inflammatory effect (determined by IL-1{alpha} release) were verified at both time points and correlated to PII values. The best correlation (R {sup 2} = 0.831) was seen with LDH leakage test. Based on obtained data, chemicals were classified according to criteria defined by EU and OECD. From 12 chemicals, only two were incorrectly classified according to OECD criteria when using LDH leakage and IL-1{alpha} release as irritation markers. At the end of experiment, chemical-treated ROC cultures were fixed and histological changes were assessed. Typical signs for irritation were lightly stained cytoplasm, condensed nuclei, cellular vacuolization, eosinophilic cytoplasms, and blebbing. These irritation effects of chemicals were graded visually into four classes (A-D). The extent of morphological perturbations of the cultures mostly correlated with PII. The present results indicate the validity of the ROC model in predicting skin irritation potential of chemicals and show that the use of set of irritation markers with different mechanistic responses gives more information on irritation than if only one marker was used.

  1. Construction of three-dimensional dermo-epidermal skin equivalents using cell coating technology and their utilization as alternative skin for permeation studies and skin irritation tests.

    PubMed

    Akagi, Takami; Nagura, Mayuka; Hiura, Ayami; Kojima, Hajime; Akashi, Mitsuru

    2017-03-23

    In vitro generated human skin equivalents are generating interest as promising tools in basic research, as alternatives to animal testing and for clinical applications in regenerative medicine. For prediction of skin irritation and corrosion, three-dimensional (3D) human skin equivalents consisting of differentiated human keratinocytes have been developed and some models have been internationally accepted. However, more delicate assessments using full-thickness skin models, such as skin sensitization tests cannot be performed because of the lack of a dermis containing fibroblasts or appendages. In a previous study, we developed dermo-epidermal human skin equivalents (DESEs) using a cell coating technique, which employs cell surface coating by layer-by-layer (LbL) assembled extracellular matrix (ECM) films. The DESEs with dermis consisting of normal human dermal fibroblasts (NHDF) and epidermis consisting of human keratinocytes (KC) were easily fabricated by using this technology. In this study, the constructed DESEs were evaluated as an alternative skin for skin permeation and irritation tests. A good relationship of permeability coefficient of chemicals was observed between the DESEs and human skin data. We investigated whether the DESEs, a new in vitro skin model, are able to identify skin irritant and non-irritant substances among 20 reference chemicals. It was confirmed that the DESEs are applicable to skin irritation testing as defined in the European Centre for the Validation of Alternative Methods (ECVAM) Performance Standard (OECD Test Guideline 439). We further studied the construction of the DESEs with density-controlled blood capillary networks using human umbilical vein endothelial cells (HUVEC). The results suggest that DESEs allowing incorporation of skin appendages are more promising alternatives to animal testing, and can be applied to the design of physiologically relevant in vitro skin models.

  2. 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.

  3. Ability of moisturizers to reduce dry skin and irritation and to prevent their return.

    PubMed

    Simion, F Anthony; Abrutyn, Eric S; Draelos, Zoe D

    2005-01-01

    Assays of moisturizer efficacy have traditionally focused on a moisturizer's ability to alleviate dry skin. More recently, a moisturizer's ability to prevent primary irritation has been recognized. To assess and compare the ability of moisturizers to alleviate skin dryness and primary irritation, as well as prevent their return, four controlled-application clinical (in vivo) studies were carried out: hand-wash test, regression test, reduction in pre-existing irritation study, and prevention-of-irritation studies. Overall conclusions were confirmed in a home-use clinical (validation) study of people suffering from mild eczema. The controlled in vivo studies demonstrate that: (a) a moisturizer can alleviate skin dryness and irritation, and prevent their return; and (b) the efficacy of different moisturizers can be differentiated, based on their composition. The home-use study results demonstrated that the most effective moisturizer identified by the controlled-application studies was highly effective against the signs of eczema. In vivo modeling of moisturizer efficacy enables assessment and optimization of different benefits separately, while predicting the quantitative and perceived (observed) relevance of the benefits the moisturizer delivers to consumers.

  4. 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.

  5. Inhibition of retinoic acid-induced skin irritation in calorie-restricted mice.

    PubMed

    Varani, James; Bhagavathula, Narasimharao; Aslam, Muhammad Nadeem; Fay, Kevin; Warner, Roscoe L; Hanosh, Andrew; Barron, Adam G; Miller, Richard A

    2008-01-01

    Mice on a calorie-restricted (CR) diet (total calories restricted to 70% of ad libitum; AL) for periods of time ranging from 3 to 18 months were examined for response to topical treatment with all-trans retinoic acid (RA). Daily application of a 0.1% solution of RA to the shaved skin of UM-HET3 mice on an AL diet produced a severe irritation that was evident by day 4, maximal at day 7-8 and still detectable at day 14. Skin irritation was characterized by redness, dryness, flaking and failure of the hair to grow at the treated site. In CR mice, the same treatment produced little detectable irritation. Animals were sacrificed at the end of the retinoid-treatment period (day 7 or day 14) and skin from these animals was examined histologically. In both AL and CR mice, a similar degree of epidermal hyperplasia was observed. Numerous inflammatory cells (mononuclear cells and granulocytes) were present in the skin of both groups. Occasional S100-positive cells (presumably Langerhans cells) were also observed in the epidermis of skin from both groups. S100-positive cells were also observed in the dermis. When skin from CR and AL mice was incubated in organ culture for 3 days (on day 7 after initiation of RA treatment), similar levels of four different pro-inflammatory cytokines were found in the conditioned medium. Soluble type I collagen levels were also similar. In contrast, the level of matrix metalloproteinase-9 was lower in the conditioned medium of skin from CR mice than in conditioned medium from skin cultures of AL mice. Taken together, these studies suggest that CR may provide a way to mitigate the irritation that normally accompanies RA treatment without compromising the beneficial effects of retinoid use. CR appears to exert a protective effect at the target tissue level rather than by a reduction in pro-inflammatory events, per se.

  6. Evaluation of a quantitative clinical method for assessment of sensory skin irritation.

    PubMed

    Robinson, M K; Perkins, M A

    2001-10-01

    Sensory skin irritation refers to the myriad of symptomatic complaints (e.g., sting and burn) frequently associated with inflammatory skin conditions or skin intolerance to various chemicals or finished products. Sensory irritation is an important factor in consumer acceptance of the products that they buy and use; however, from a safety testing and risk assessment standpoint, it has been difficult to evaluate. Recently, methods have been developed to more quantitatively assess sensory irritation using a semantically-labeled scale of sensation intensity, the labeled magnitude (LM) scale. Using this device, studies were conducted to determine if test subjects' perceptions of recalled or imagined sensory responses (from a series of survey questions) were related to their actual sensory reactivity to chemical challenge. Subjects were presented with 15 skin sensation scenarios of varying intensities and asked to record their self-perceived recalled or imagined responses using the LM scale. Individual and mean responses to each of the 15 survey questions were compared within and across studies. Considerable variation was seen between subjects' responses to the questions, particularly for questions pertaining to stronger stimuli (e.g., scalding water or skin lacerations). There was also little consistency seen in the pattern of individual responses across the questions. However, among 4 different study populations, the group mean scores for each of the 15 survey questions showed a high degree of consistency. Also, in spite of the variability in perceived responses to the recalled/imagined skin sensations, statistically significant dose-response and time-response patterns were observed in chemical (lactic acid and capsaicin) challenge studies. In one capsaicin study, a direct relationship was observed, among 83% of the study subjects, between the mean recall intensity scores and actual responses to subsequent capsaicin challenge. This pattern was not seen in a lactic acid

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

    PubMed Central

    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. PMID:26273696

  8. 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.

  9. Innovative approaches to avoid electric shaving-induced skin irritation.

    PubMed

    Rietzler, M; Maurer, M; Siebenhaar, F; Angelino, S; Handt, J; Burghardt, R; Smetana, H

    2016-06-01

    Globally, millions of men regularly remove their facial hair using an electric shaver. Over the course of several decades, the concept of an electric shaver has evolved from a relatively simple hand-powered apparatus to a technologically advanced device designed to provide the user with an optimum shaving experience. This requires a careful balance between robust removal of hair and skin comfort. By incorporating advanced scientific measurement and imaging technology into clinical testing, insights are being gained into skin comfort issues associated with hair removal practices. This study describes new research insights that have guided the development of electric shaving technology. These innovative features are designed to maximize hair removal and minimize the impact on skin health, thus enabling new levels of shaving efficacy and comfort to be attained. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  10. In vitro human skin irritation test for evaluation of medical device extracts.

    PubMed

    Casas, J W; Lewerenz, G M; Rankin, E A; Willoughby, J A; Blakeman, L C; McKim, J M; Coleman, K P

    2013-12-01

    The aim of this study was to determine if the EpiDerm™ reconstructed human skin model (MatTek Corp.) could be an acceptable alternative to the ISO 10993-required rabbit skin irritation test for assessing medical device biocompatibility. Eleven medical device polymers were tested. Four extracts were prepared per polymer, two each with saline and sesame oil; half were spiked with two R-38 irritants, lactic acid for saline extracts and heptanoic acid for the sesame oil extracts. Tissue viability was assessed by MTT reduction and the proinflammatory response was assessed by IL-1α release. LOAELs of 2% for lactic acid in saline and 0.7% for heptanoic acid in sesame oil were determined. A cell viability reduction of >50% was indicative of skin irritation. Cells exposed to saline extracts spiked with 3.25% lactic acid had significantly reduced mean cell viabilities (12.6-17.2%). Cells exposed to sesame oil extracts spiked with 1.25% heptanoic acid also exhibited reduced mean cell viabilities (25.5%-41.7%). All spiked cells released substantial amounts of IL-1α (253.5-387.4pg/ml) signifying a proinflammatory response. These results indicate that the EpiDerm™ model may be a suitable in vitro replacement for the assessment of the irritation potential of medical device extracts.

  11. Separation of retinoid-induced epidermal and dermal thickening from skin irritation.

    PubMed

    Varani, James; Fligiel, Helene; Zhang, Jian; Aslam, Muhammad Nadeem; Lu, Yi; Dehne, Lindsay A; Keller, Evan T

    2003-11-01

    The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9- cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all- trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.

  12. 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.

  13. In vivo testing of silver treated fibers for the evaluation of skin irritation effect and hypoallergenicity.

    PubMed

    Paladini, F; Sannino, A; Pollini, M

    2014-07-01

    Textiles are a fertile breeding ground for a multitude of micro-organisms under appropriate conditions of moisture and temperature. The broad-spectrum biocide properties of silver are well known and many technologies have been developed so far to treat textiles with silver. The efficacy of the silver deposition technology presented in this article has been already demonstrated in previous works, where the strong adhesion of silver nanoparticles to the substrate and their antibacterial capability have been assessed. This work focuses on the evaluation of any possible interaction of silver treated cotton with human skin, in terms of skin irritation and hypoallergenicity. Moreover, the presence of silver and the antibacterial capability against Gram positive and Gram negative bacteria, namely Staphylococcus aureus and Escherichia coli, were verified even after several washing cycles in order to develop a product with long-term antibacterial capability and no adverse effects in terms of skin irritation and hypoallergenicity. © 2013 Wiley Periodicals, Inc.

  14. Significant differences in skin irritation by common suture materials assessed by a comparative computerized objective method.

    PubMed

    Parara, Sofia M; Manios, Andreas; de Bree, Eelco; Tosca, Androniki; Tsiftsis, Dimitris D

    2011-03-01

    Erythema can be described only through subjective evaluation, except when it is quantified by digital image analysis software. Using such software, the authors performed comparisons of the erythema produced after skin closure of clean surgical wounds. Five suture materials were compared with respect to the local skin irritation that was caused. Different quantities of erythema are produced by suture material after the skin closure of clean surgical wounds. The authors present an objective method of measuring how unreactive a suture material is in comparison with another when applied to the skin. The suture materials polydioxanone, polypropylene blue, polyamide 6, metallic clips, and polyglactin were compared in the present study. Digital photographs of 100 patients were compared by means of software, evaluating red color superiority (mean value of red color) in the region surrounding the wound. The least to most irritation caused to the skin by different suture materials was established for paired data. The Kolmogorov-Smirnov criterion and the Wilcoxon signed rank test were used. Polydioxanone was found to have the best performance, followed in order by polyglactin, polyamide, polypropylene, and metallic clips. Immediately after suture removal, differences between the effects of suture materials were statistically significant on postoperative day 10. Absorbable sutures can be used in skin closure of clean surgical wounds and can produce less erythematous reaction than nonabsorbable ones. Digital image analysis is a reliable method of quantitative evaluation of skin erythema resulting after skin closure of surgical wounds.

  15. 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

  16. Primary irritant reactions in the skin of the pika, Ochotona rufescens rufescens.

    PubMed

    Sakai, T; Kodama, Y; Yamamoto, H; Horiuchi, S; Nomura, T

    1989-10-01

    The skin of the pika (Ochotona rufescens rufescens) was found to be remarkably sensitive to the primary irritation of sodium hydroxide, as compared with the skin of the rabbit. After exposure to 0.1 N sodium hydroxide for 24 hr, the pika skin showed severe erosion, ulceration and necrosis as well as crust formation and hyperkeratosis with vascular dilation, and cell infiltration. The changes appeared already within 1 hr after 1 N or 3 hr after 0.1 N sodium hydroxide application. After application of acetic acid, changes were apparent while less remarkable.

  17. 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.

  18. Calamine lotion to reduce skin irritation in children with cast immobilisation.

    PubMed

    Mak, May Fong; Li, Wenyun; Mahadev, Arjandas

    2013-08-01

    PURPOSE. To evaluate the effect of calamine lotion in reducing skin irritation in children with cast immobilisation and to identify factors correlating with skin irritation. METHODS. 250 children aged 6 to 15 years who underwent cast immobilisation for limb fractures were assigned into calamine (n=122) and non-calamine (n=128) groups. Data were collected at the time the cast was applied and removed. Potential confounders (gender, age, race, medical history, drug allergy, cast type, duration of casting, and extent of itch prior to casting) were identified. Each patient graded his levels of itch, sweat, and heat using a 5-point scale (with 5 indicating most severe). The on-duty plaster technician recorded the presence and type of skin lesions (blisters, wounds, or others) during cast removal. RESULTS. Children in the calamine group were less likely to develop skin lesions (1 vs. 9, odds ratio [OR]=0.115, p=0.009), had less itch during casting (mean difference=0.74, p<0.0001), had a greater decrease in the itch level (mean difference=0.84, p<0.0001), and had lower sweat levels (p=0.048). After adjusting for confounders, the chance of developing skin lesions remained lower in the calamine group (OR=0.063, p=0.003). Being an older child and having shorter duration of casting were associated with presence of skin lesions. The odds for having skin lesions increased by 39.2% per year increase in age (OR=1.392, p=0.04) and decreased by 9.4% per day increase in casting duration (OR=0.906, p=0.03). The decrease in itch level remained significantly greater in the calamine group after adjusting for confounders (p<0.0001). CONCLUSION. Calamine lotion may reduce skin irritation in children with full casts.

  19. Alstonia scholaris R. Br. Significantly Inhibits Retinoid-Induced Skin Irritation In Vitro and In Vivo

    PubMed Central

    Lee, Soo-Jin; Cho, Sun-A; An, Su-Sun; Na, Yong-Joo; Park, Nok-Hyun; Kim, Han-Sung; Lee, Chan-Woo; Kim, Han-Kon; Kim, Eun-Kyung; Jang, Young-Pyo; Kim, Jin-Woong

    2012-01-01

    Topical retinoids inhibit matrix metalloproteinases and accelerate collagen synthesis, thereby triggering antiaging effects in the skin. However, topical retinoids can cause severe skin reactions, including scaling, erythema, papules, and inflammation. The present study demonstrates that the ethanolic bark extract of Alstonia scholaris R. Br. can significantly inhibit all-trans retinoic acid-induced inflammation in human HaCat keratinocyte cells. Furthermore, two representative retinoid-induced proinflammatory cytokines, monocyte chemoattractant protein-1 and interleukin-8, were significantly suppressed by A. scholaris extract (by 82.1% and 26.3% at 100 ppm, and dose-dependently across the tested concentrations) in vitro. In a cumulative irritation patch test, A. scholaris extract decreased retinol-induced skin irritation, while strengthening the ability of retinoids to inhibit matrix metalloproteinase-1 expression, which is strongly associated with aging effects. These results suggest that A. scholaris is a promising compound that may increase the antiaging function of retinoids while reducing their ability to cause skin irritation. PMID:21912567

  20. Alstonia scholaris R. Br. Significantly Inhibits Retinoid-Induced Skin Irritation In Vitro and In Vivo.

    PubMed

    Lee, Soo-Jin; Cho, Sun-A; An, Su-Sun; Na, Yong-Joo; Park, Nok-Hyun; Kim, Han-Sung; Lee, Chan-Woo; Kim, Han-Kon; Kim, Eun-Kyung; Jang, Young-Pyo; Kim, Jin-Woong

    2012-01-01

    Topical retinoids inhibit matrix metalloproteinases and accelerate collagen synthesis, thereby triggering antiaging effects in the skin. However, topical retinoids can cause severe skin reactions, including scaling, erythema, papules, and inflammation. The present study demonstrates that the ethanolic bark extract of Alstonia scholaris R. Br. can significantly inhibit all-trans retinoic acid-induced inflammation in human HaCat keratinocyte cells. Furthermore, two representative retinoid-induced proinflammatory cytokines, monocyte chemoattractant protein-1 and interleukin-8, were significantly suppressed by A. scholaris extract (by 82.1% and 26.3% at 100 ppm, and dose-dependently across the tested concentrations) in vitro. In a cumulative irritation patch test, A. scholaris extract decreased retinol-induced skin irritation, while strengthening the ability of retinoids to inhibit matrix metalloproteinase-1 expression, which is strongly associated with aging effects. These results suggest that A. scholaris is a promising compound that may increase the antiaging function of retinoids while reducing their ability to cause skin irritation.

  1. Anti-melasma codrug of retinoic acid assists cutaneous absorption with attenuated skin irritation.

    PubMed

    Hsieh, Pei-Wen; Hung, Chi-Feng; Lin, Chih-Hung; Huang, Chang-Wei; Fang, Jia-You

    2017-05-01

    Melasma treatment with combined retinoic acid (RA) and hydroquinone (HQ) usually causes unsatisfactory outcomes and safety concerns. This study attempted to evaluate the cutaneous absorption and skin tolerance of the codrug conjugated with RA and HQ via ester linkage. The codrug's permeation of the pig skin was estimated using Franz diffusion cell. The codrug and parent drugs were comparatively examined for anti-inflammatory activity and tyrosinase inhibition. In vivo cutaneous irritation was assessed on nude mouse skin. Chemical conjugation of RA with HQ increased the lipophilicity and thus the skin absorption. The codrug absorption produced a 5.5- and a 60.8-fold increment compared to RA skin deposition at an equimolar (1.2mM) and saturated solubility dose, respectively. The cumulative amount of HQ derived from the codrug in the receptor was comparable to or less than that of topically applied HQ. The RA-HQ codrug was partly hydrolyzed on penetrating the skin. The hydrolysis rate in intact skin was significantly lower than that in esterase medium and skin homogenates. The codrug showed an interleukin (IL)-6 inhibition activity comparable to RA. A therapeutic index 6-fold greater than RA was obtained with the topical codrug. The tyrosinase inhibition percentage of the codrug and HQ was 13% and 21%, respectively. The skin tolerance test determined by transepidermal water loss (TEWL), redness, and histopathology had exhibited minor skin irritation caused by the codrug compared to the physical mixture of RA and HQ at an equivalent dose. Topical codrug delivery not only promoted RA absorption, but also diminished the adverse effects of the parent agents.

  2. Increased risk for irritable bowel syndrome after acute diverticulitis.

    PubMed

    Cohen, Erica; Fuller, Garth; Bolus, Roger; Modi, Rusha; Vu, Michelle; Shahedi, Kamyar; Shah, Rena; Atia, Mary; Kurzbard, Nicole; Sheen, Victoria; Agarwal, Nikhil; Kaneshiro, Marc; Yen, Linnette; Hodgkins, Paul; Erder, M Haim; Spiegel, Brennan

    2013-12-01

    Individuals with diverticulosis frequently also have irritable bowel syndrome (IBS), but there are no longitudinal data to associate acute diverticulitis with subsequent IBS, functional bowel disorders, or related emotional distress. In patients with postinfectious IBS, gastrointestinal disorders cause long-term symptoms, so we investigated whether diverticulitis might lead to IBS. We compared the incidence of IBS and functional bowel and related affective disorders among patients with diverticulitis. We performed a retrospective study of patients followed up for an average of 6.3 years at a Veteran's Administration medical center. Patients with diverticulitis were identified based on International Classification of Diseases, 9th revision codes, selected for the analysis based on chart review (cases, n = 1102), and matched with patients without diverticulosis (controls, n = 1102). We excluded patients with prior IBS, functional bowel, or mood disorders. We then identified patients who were diagnosed with IBS or functional bowel disorders after the diverticulitis attack, and controls who developed these disorders during the study period. We also collected information on mood disorders, analyzed survival times, and calculated adjusted hazard ratios. Cases were 4.7-fold more likely to be diagnosed later with IBS (95% confidence interval [CI], 1.6-14.0; P = .006), 2.4-fold more likely to be diagnosed later with a functional bowel disorder (95% CI, 1.6-3.6; P < .001), and 2.2-fold more likely to develop a mood disorder (CI, 1.4-3.5; P < .001) than controls. Patients with diverticulitis could be at risk for later development of IBS and functional bowel disorders. We propose calling this disorder postdiverticulitis IBS. Diverticulitis appears to predispose patients to long-term gastrointestinal and emotional symptoms after resolution of inflammation; in this way, postdiverticulitis IBS is similar to postinfectious IBS. Copyright © 2013 AGA Institute. Published by

  3. 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.

  4. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

    PubMed Central

    Eberhard, Yanina; Ortiz, Susana; Ruiz Lascano, Alejandro; Kuznitzky, Raquel; Serra, Horacio Marcelo

    2004-01-01

    Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC) has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible for inducing Irritant Contact Dermatitis (ICD). Results Eleven normal individuals were challenged with different chemical or physical irritants. Two patients with Allergic Contact Dermatitis (ACD) were also challenged with the relevant antigen in order to have a positive control for CCL21 expression. Macroscopic as well as microscopic responses were evaluated. We observed typical ICD responses with mostly mononuclear cells in perivascular areas, but a predominance of polymorphonuclear cells away from the inflamed blood vessels and in the epidermis at 24 hours. Immunohistochemical studies showed up-regulation of CCL21 by lymphatic endothelial cells in all the biopsies taken from ICD and ACD lesions compared to normal skin. Kinetic study at 10, 48, 96 and 168 hours after contact with a classical irritant (sodium lauryl sulphate) showed that the expression of CCL21 was increased in lymphatic vessels at 10 hours, peaked at 48 hours, and then gradually declined. There was a strong correlation between CCL21 expression and the macroscopic response (r = 0.69; p = 0.0008), but not between CCL21 and the number of infiltrating cells in the lesions. Conclusions These results provide new evidence for the role of CCL21 in inflammatory processes. Since the up-regulation of this chemokine was observed in ICD and ACD, it is tempting to speculate that this mechanism operates independently of the type of dermal insult, facilitating the emigration of CCR7+ cells. PMID:15109401

  5. 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..

  6. Skin Corrosion and Irritation Test of Nanoparticles Using Reconstructed Three-Dimensional Human Skin Model, EpiDermTM

    PubMed Central

    Kim, Hyejin; Choi, Jonghye; Lee, Handule; Park, Juyoung; Yoon, Byung-Il; Jin, Seon Mi; Park, Kwangsik

    2016-01-01

    Effects of nanoparticles (NPs) on skin corrosion and irritation using three-dimensional human skin models were investigated based on the test guidelines of Organization for Economic Co-operation and Development (OECD TG431 and TG439). EpiDermTM skin was incubated with NPs including those harboring iron (FeNPs), aluminum oxide (AlNPs), titanium oxide (TNPs), and silver (AgNPs) for a defined time according to the test guidelines. Cell viabilities of EpiDermTM skins were measured by the 3-(4, 5-dimethylthi-azol-2-yl)-2.5-diphenyltetrazolium bromide based method. FeNPs, AlNPs, TNPs, and AgNPs were non-corrosive because the viability was more than 50% after 3 min exposure and more than 15% after 60 min exposure, which are the non-corrosive criteria. All NPs were also non-irritants, based on viability exceeding 50% after 60 min exposure and 42 hr post-incubation. Release of interleukin 1-alpha and histopathological analysis supported the cell viability results. These findings suggest that FeNPs, AlNPs, TNPs, and AgNPs are ‘non-corrosive’ and ‘non-irritant’ to human skin by a globally harmonized classification system. PMID:27818733

  7. Hydrophobically modified polymers can minimize skin irritation potential caused by surfactant-based cleansers

    PubMed Central

    Draelos, Zoe; Hornby, Sidney; Walters, Russel M; Appa, Yohini

    2013-01-01

    Summary Introduction The addition of hydrophobically modified polymers (HMPs) to cleansers that contain surfactants can create polymer–surfactant complexes that are less irritating to the skin than commercially available mild cleansers. Our objective was to compare the tolerability and efficacy of a test foaming liquid facial cleanser containing HMPs with a commercial liquid nonfoaming facial cleanser in women with sensitive skin. Methods In this randomized, prospective, double-blind, comparative study, women (n = 20 per group) with mild-to-moderate atopic dermatitis (AD), eczema, acne, or rosacea used a test gentle foaming liquid facial cleanser containing HMPs or a commercial gentle liquid nonfoaming facial cleanser daily for 3 weeks. Investigators assessed irritation and skin condition. Study subjects also assessed their skin properties and the performance of each cleanser. Results Clinicians as well as study subjects consistently rated the test cleanser as effective or slightly more effective at improving symptoms than the commercial cleanser, although no significant differences between groups were observed. At weeks 1 and 3, respectively, more users of the commercial cleanser reported irritation (20% and 10%) than users of the test cleanser (5% and 5%). In addition, subject self-assessments of skin condition and cleansing properties were slightly more improved with the test cleanser than with the commercial cleanser. Conclusions Both the test foaming cleanser containing HMPs and the commercial nonfoaming cleanser were effective and well accepted by most women in the study. Improvements were observed by both clinicians and subjects in the group using the test cleanser containing HMPs in all evaluated skin categories. PMID:24305430

  8. Hydrophobically modified polymers can minimize skin irritation potential caused by surfactant-based cleansers.

    PubMed

    Draelos, Zoe; Hornby, Sidney; Walters, Russel M; Appa, Yohini

    2013-12-01

    The addition of hydrophobically modified polymers (HMPs) to cleansers that contain surfactants can create polymer-surfactant complexes that are less irritating to the skin than commercially available mild cleansers. Our objective was to compare the tolerability and efficacy of a test foaming liquid facial cleanser containing HMPs with a commercial liquid nonfoaming facial cleanser in women with sensitive skin. In this randomized, prospective, double-blind, comparative study, women (n = 20 per group) with mild-to-moderate atopic dermatitis (AD), eczema, acne, or rosacea used a test gentle foaming liquid facial cleanser containing HMPs or a commercial gentle liquid nonfoaming facial cleanser daily for 3 weeks. Investigators assessed irritation and skin condition. Study subjects also assessed their skin properties and the performance of each cleanser. Clinicians as well as study subjects consistently rated the test cleanser as effective or slightly more effective at improving symptoms than the commercial cleanser, although no significant differences between groups were observed. At weeks 1 and 3, respectively, more users of the commercial cleanser reported irritation (20% and 10%) than users of the test cleanser (5% and 5%). In addition, subject self-assessments of skin condition and cleansing properties were slightly more improved with the test cleanser than with the commercial cleanser. Both the test foaming cleanser containing HMPs and the commercial nonfoaming cleanser were effective and well accepted by most women in the study. Improvements were observed by both clinicians and subjects in the group using the test cleanser containing HMPs in all evaluated skin categories. © 2013 The Authors Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.

  9. Effects of glycerol on human skin damaged by acute sodium lauryl sulphate treatment.

    PubMed

    Atrux-Tallau, Nicolas; Romagny, Céline; Padois, Karine; Denis, Alain; Haftek, Marek; Falson, Françoise; Pirot, Fabrice; Maibach, Howard I

    2010-08-01

    Glycerol, widely used as humectant, is known to protect against irritants and to accelerate recovery of irritated skin. However, most studies were done with topical formulations (i.e. emulsions) containing glycerol in relatively high amounts, preventing drawing conclusions from direct effects. In this study, acute chemical irritations were performed on the forearm with application of a 10% sodium lauryl sulphate (SLS) aqueous solution under occlusion for 3 h. Then, glycerol aqueous solutions from 1 to 10% were applied under occlusion for 3 h. After elimination of moist excess consecutive to occlusive condition, in ambient air for 15 and 30 min, skin barrier function was investigated by dual measurement of skin hydration and transepidermal water loss (TEWL). Treatments with SLS solution under occlusion significantly increased TEWL and decreased skin hydration as assessed by capacitance measurements. The SLS irritant property was raised by the occlusion and the water barrier function as well as water content appeared impaired. Recovery with glycerol at low doses was remarkable through a mechanism that implies its hygroscopic properties and which is saturable. This precocious effect acts through skin rehydration by enhancing water-holding capacity of stratum corneum that would facilitate the late physiological repair of impaired skin barrier. Thus, glycerol appears to substitute for natural moisturizing factors that have been washed out by the detergent action of SLS, enhancing skin hydration but without restoring skin barrier function as depicted by TEWL values that remained high. Thus, irritant contact dermatitis treated with glycerol application compensate for skin dehydration, favouring physiological process to restore water barrier function of the impaired skin. Empirical use of glycerol added topical formulations onto detergent altered skin was substantiated in the present physicochemical approach.

  10. Encapsulation of Mentha Oil in Chitosan Polymer Matrix Alleviates Skin Irritation.

    PubMed

    Mishra, Nidhi; Rai, Vineet Kumar; Yadav, Kuldeep Singh; Sinha, Priyam; Kanaujia, Archana; Chanda, Debabrata; Jakhmola, Apurva; Saikia, Dharmendra; Yadav, Narayan Prasad

    2016-04-01

    Mentha spicata L. var. viridis oil (MVO) is a potent antifungal agent, but its application in the topical treatment is limited due to its irritancy and volatility. It was aimed to develop more efficient, chitosan-incrusted MVO microspheres with reduced volatility and lesser irritancy and to dispense it in the form of ointment. Simple coacervation technique was employed to microencapsulate MVO in chitosan matrix. Morphological properties and polymer cross-linking were characterized by scanning electron microscopy and differential scanning calorimetry, respectively. Optimization was carried out on the basis of entrapment efficiency (EE) using response surface methodology. Well-designed microspheres having smooth surface and spherical shape were observed. EE (81.20%) of optimum batch (R21) was found at 1.62% w/v of cross-linker, 5.4:5 of MVO to chitosan ratio and at 1000 rpm. R21 showed 69.38 ± 1.29% in vitro MVO release in 12 h and 96.92% retention of MVO in microspheres even after 8 week. Ointments of PEG 4000 and PEG 400 comprising MVO (F1) and R21 (F2) were developed separately. F2 showed comparatively broader zone of growth inhibition (13.33 ± 1.76-18.67 ± 0.88 mm) and less irritancy (PII 0.5833, irritation barely perceptible) than that of F1. F2 was able to avoid the direct contact of mild irritant MVO with the skin and to reduce its rapid volatility. Controlled release of MVO helped in lengthening the duration of availability of MVO in agar media and hence improved its therapeutic efficacy. In conclusion, a stable and non-irritant formulation with improved therapeutic potential was developed.

  11. Coumarin derivatives, but not coumarin itself, cause skin irritation via topical delivery.

    PubMed

    Pan, Tai-Long; Wang, Pei-Wen; Aljuffali, Ibrahim A; Leu, Yann-Lii; Hung, Yi-Yun; Fang, Jia-You

    2014-04-21

    Coumarin and its derivatives are widely employed as a fragrance in cosmetics and skin care products. The skin absorption level and possible disruption to the skin by topical application of coumarins were evaluated in this study. Percutaneous absorption of osthole, daphnoretin, coumarin, byakangelicin, and 7-hydroxycoumarin was assessed in vitro and in vivo. Skin physiology measurements and immunoblotting were utilized as methodologies for validating toxicity. The relationship between structures and permeation/toxicity of coumarins was elucidated. Both equimolar concentration and saturated solubility in 30% ethanol were used as the applied dose. Osthole with the most lipophilic characteristic demonstrated the greatest skin accumulation, followed by coumarin and 7-hydroxycoumarin. Coumarin was the permeant with the highest flux across the skin. The trend of in vivo deposition was consistent with that of the in vitro profiles. Skin uptake of osthole was 8-fold higher than that of coumarin. Hair follicles played a significant role as a pathway for transport of coumarin according to the examination of follicular accumulation. Osthole and 7-hydroxycoumarin slightly, but significantly, enhanced transepidermal water loss after a consecutive 5-day administration. The immunoblotting profiling verified the role of proliferation in skin damage induced by osthole, byakangelicin, and 7-hydroxycoumarin. The proliferation-related proteins examined in this work included glucose-regulated proteins, cytokeratin, and C-myc. Daphnoretin and coumarin showed a negligible alteration on protein biomarkers. The experimental results suggested that skin irritation caused by coumarins was mainly derived from the analogs but not from coumarin itself.

  12. Assessment of skin absorption and irritation potential of arachidonic acid and glyceryl arachidonate using in vitro diffusion cell techniques.

    PubMed

    Eppler, A R; Kraeling, M E K; Wickett, R R; Bronaugh, R L

    2007-11-01

    Arachidonic acid (AA), a precursor of pro-inflammatory mediators, and its glycerin ester, glyceryl arachidonate (GA), are reportedly used in cosmetic products. In vitro skin penetration of AA and GA and GA's ester hydrolysis was determined in flow-through diffusion cells. AA penetration with human and rat skin was 19.5% and 52.3% of the applied dose respectively, a substantial amount of which remained in the skin at 24h. Similar penetration results were obtained with GA in human skin. However, GA penetration through cultured skin (EpiDerm) was 51% of the applied dose, almost all of which appeared in the receptor fluid. At least 27.8% of GA penetrating skin was hydrolyzed to AA. In vitro methods were used to assess skin irritation in diffusion cells. Skin irritation of AA, sodium lauryl sulfate (SLS), and Tween 80 was determined by changes in transepidermal water loss (TEWL), skin viability (3-(4,5-dimethylthiaxol-2-yl)-2,5-diphenyltetrazolium bromide, MTT, formation), and cytokine release (IL-1alpha). SLS irritation was much less pronounced in an emulsion versus an aqueous vehicle. No significant irritation was observed in vitro from AA in an emulsion. This work predicts that AA would penetrate human skin in vivo and that it could be formed in skin from topically applied GA.

  13. 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

  14. 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.

  15. Tolerance profile of a sterile moisturizer and moisturizing cleanser in irritated and sensitive skin.

    PubMed

    Vie, K; Pons-Guiraud, A; Dupuy, P; Maibach, H

    2000-09-01

    This study evaluates the tolerance of preservative free sterile cleanser and sterile moisturizer in irritated and sensitive face skin. An exploratory, open-label study using the cleanser and the moisturizer in combination was performed with 98 patients with a documented history of allergic contact dermatitis. The 2 products could each be used once or twice daily for 28 days. The assessment parameters at baseline and end of treatment (day 28) included the intensity of erythema, dryness/scaling by the investigator and subjective signs (burning, pruritus and stinging), according to a defined 4-point scale (absent to severe). In addition, a global assessment of the change from baseline and the overall tolerance of the products were performed by the investigator at the end of treatment. Ninety-four patients were included for the efficacy analysis and 96 patients for the safety analysis. At baseline, a majority of patients expressed some degree of erythema (63%), and dryness/scaling (56%). Fewer patients experienced subjective signs at baseline (44%). At the end of treatment, the results showed a statistically significant improvement of all the objective signs of irritated skin (P = .0001, Mac Nemar test), as well as the subjective signs of sensitive skin (P < 0.02). This was confirmed by the overall investigator assessment, showing an excellent or good response in 90% of the patients. In the safety analysis, 1 patient developed contact allergy to 1 ingredient of the test products (carbomer), and 3 patients exacerbated their dermatitis. Taken together, these results suggest that adequately formulated cosmetics might reduce both irritated and sensitive skin, with clinical improvement of dryness, erythema and stinging.

  16. [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.

  17. Acute inhalation toxicity and sensory irritation of dimethylamine. [Rats, mice

    SciTech Connect

    Steinhagen, W.H.; Swenberg, J.A.; Barrow, C.S.

    1982-06-01

    The sensory irritation potential of dimethylamine (DMA) inhalation on male Fischer-344 rats and male Swiss-Webster mice was evaluated by measuring the reflex decrease in respiratory rate. In addition, the six hour LC/sub 50/ for rats exposed to dimetylamine was established. Groups of 3 or 4 rats and mice were exposed for 10 minutes to concentrations of DMA ranging from 49 to 1576 ppm during which time the respiratory rate was monitored and recorded. Sensory irritation concentration-response curves were obtained and RD/sub 50/ values (concentration which elicits a 50% decrease in respiratory rate) were determined to be 573 and 511 ppm for rats and mice, respectively. In another set of experiments seven groups of male rats were exposed to concentrations of DMA ranging from 600 to 6119 ppm for six hours. Mortality counts were made during and for 48 hours post exposure. The six hour LC/sub 50/ was determined to be 4540 ppm. Histopathologic examination of the respiratory tract revealed concentration related changes ranging from ulceration and necrosis to rhinitis, tracheitis, and emphysema. Overall, DMA was found to be less potent as a sensory irritant than other airborne irritants.

  18. Skin irritation and histopathologic alterations in rats exposed to lightstick contents, UV radiation and seawater.

    PubMed

    Ivar do Sul, Juliana A; Rodrigues, Obirajara; Santos, Isaac R; Fillmann, Gilberto; Matthiensen, Alexandre

    2009-10-01

    Lightsticks are fishing gadgets that provide fluorescent lighting when two organic solutions are mixed. In NE Brazil, low-income coastal residents ignore their conventional use and collect lightsticks stranded on beaches. The lightstick solution is then used for various purposes, including direct human skin exposure. We assessed the reactions and possible cell damages on the skin of Wistar rats. Animals were exposed to lightstick contents, UV radiation and/or seawater. Lightstick exposure led to erythemas, oedemas and vesicles. Histopathologic alterations included proliferation of the epidermis and inflammatory infiltrates. In spite of the short time of experimentation (4 days), the rats exposed to the lightstick content alone and together with UV radiation and/or seawater provided evidence of irritation/alteration reactions that may evolve into skin cancer. Our results demonstrated a few of the potential problems associated with lightstick dumping into the ocean and highlight the need for further investigations about this new type of marine pollutant.

  19. 75 FR 52755 - Draft Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Acute Bacterial Skin and Skin... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... the development of antimicrobial drugs for the treatment of acute bacterial skin and skin structure...

  20. The study of human skin irritation of a novel herbal skin care product and ingredients by human single closed patch testing.

    PubMed

    Wattanakrai, Penpun; Suwanachote, Suthida; Kulkollakarn, Sutinee; Rajatanavin, Natta

    2007-06-01

    The Government Pharmaceutical Organization of Thailand (GPO) has developed many products using liposome nanotechnology and Thai herbal extracts. Evaluate the irritation potential of GPO products on human skin using the single application closed patch test under occlusion. The authors also studied the moisturizing efficacy of a commercial curmin extract cream (GPO curmin cream). Thirty-six female volunteers were tested with 12 test materials developed by GPO including liposome, curmin extract: tetrahydrocurcuminoids (THC), and commercial curmin cream. Two and a half percent sodium dodecyl sulfate (SDS) was used as positive control. Standard Finn chambers on Scanpor tape with webril cotton were used as occlusive patch test devices. Cutaneous irritation responses were graded after patch removal and the incidence of irritation compared to the positive control was used for evaluation. Corneometer was used to measure skin hydration before and after application of curmin cream. All volunteers completed the present study. The skin irritation effects from the test materials were significantly lower (p-value < 0.001, McNemar statistic test) than the positive control. Measurement of skin hydration after twice daily application of GPO curmin cream was significantly higher (p-value < 0.001, paired t-test) than the control skin. The test materials and finished products developed by the GPO are not likely to induce skin irritation under normal conditions of use. Furthermore, twice-daily application of the commercial GPO curmin cream can significantly increase skin hydration.

  1. 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

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

    PubMed

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

    2016-12-01

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

  3. Acute local irritative effect of (2''R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic.

    PubMed

    Tone, H; Kiyosaki, T; Cuthbert, J A; Carr, S M; Aitken, R

    1986-02-01

    (2"R)-4'-O-Tetrahydropyranyladriamycin hydrochloride (THP), a new antitumor antibiotic, was administered to rabbits at a concentration from 0.02 to 0.5% by instillation, or by intracutaneous, subcutaneous or intramuscular injection to study its local irritative effect. The irritative effect of THP increased with concentration. At a concentration of 0.5%, THP was irritant to the eye, skin and muscle but at a concentration of 0.1% practically no effect was observed. The effect was equal to or lower than that of doxorubicin. An instillation of 0.5% THP caused reversible irritation effect on the eye. Slight conjunctival responses (redness and chemoisis) were observed. Rinsing reduced the irritative effect. Intracutaneous injection of 0.1 ml of 0.5% THP caused well defined, moderate erythema, surface ulceration and dermal necrosis. Cutaneous muscle necrosis also occurred. At a concentration of 0.02%, dermal necrosis and inflammatory cell infiltration were observed. Erythema, as well as muscle necrosis and calcification with giant cell reaction and inflammatory cell infiltration were observed by an intramuscular injection at a concentration of 0.5%. Subcutaneous injection of 0.5% THP showed no irritative effect.

  4. Predictive ability of reconstructed human epidermis equivalents for the assessment of skin irritation of cosmetics.

    PubMed

    Faller, C; Bracher, M; Dami, N; Roguet, R

    2002-10-01

    The aim of this study was to examine the concordance between human in vivo and in vitro skin irritation classifications of cosmetic products and to evaluate the correlations between the different parameters. For that purpose, 22 formulations from product development test series, covering the full range of in vivo scores and representing different cosmetic product classes, were tested in vivo (modified Frosch-Kligman Soap Chamber Patch Test with repetitive occlusive application) and in vitro using two epidermis equivalents commercially available as kits (EpiDerm and EPISKIN) and one in-house model (Cosmital). In vivo, skin reactions (erythema, dryness and fissures) were visually evaluated and, in addition, skin redness and transepidermal water loss (TEWL) were measured by means of technical instruments. The parameters measured in vitro were the percent cell viability in the MTT reduction assay, with ET(50) determination, and the extracellular release of the pro-inflammatory mediator IL-1alpha and of the cytosolic enzyme lactate dehydrogenase (LDH), into the culture medium collected after topical application of the products for different exposure times (time-course assay). In general, good Spearman rank correlations could be observed between the different in vivo parameters (with the exception of TEWL and dryness at day 2). Furthermore, high correlation coefficients were obtained by comparing the different in vitro parameters (except for LDH release) and different models, which allowed to conclude that the results obtained with the different reconstructed epidermis models were very similar. A comparison between in vivo and in vitro parameters resulted in the best rank correlation for ET(50), then in decreasing order, for the percent MTT viability at 16 h, the IL-1alpha release and finally, for LDH release, where the correlation was generally low. A direct comparison of the mean total scores (sum of erythema, dryness and fissures at day 5) of the 22 products with the

  5. A new reconstructed human epidermis for in vitro skin irritation testing.

    PubMed

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

    2017-08-01

    Different models of reconstructed human epidermis (RHE) are currently validated to assess skin irritation in vitro and ultimately to the animal replacement of the Draize test. The development of a new RHE model is a challenge for many laboratories, representing a potential gain of autonomy and improvement of technological knowledge. The Organization for Economic Co-operation and Development (OECD) encourages the development of new models and, for this purpose, offers a thorough guideline on quality control parameters (OECD TG 439 performance standards). This work aimed to develop an RHE model (i.e. USP-RHE) for in vitro skin irritation assays, following the OECD TG 439. The developed model presents a well-differentiated epidermis similar to the Validated Reference Methods (VRM) and to native human epidermis. Quality parameters, i.e. optical density of negative control, tissue integrity and barrier function, were similar to VRM and in accordance with OECD TG 439. Moreover, the USP-RHE model was shown to have 85,7% of specificity (6/7), 100% of sensitivity (6/6) and 92,3% of accuracy (12/13) when compared to in vivo UN GHS classification. The within-laboratory reproducibility was 92.3% (12/13). Thus, we demonstrated that USP-RHE model attends to all OECD TG 439 performance standards and is ready to be used by private and public laboratories and companies for future validation studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The influence of microemulsion structure on their skin irritation and phototoxicity potential.

    PubMed

    Rozman, Branka; Gosenca, Mirjam; Falson, Françoise; Gašperlin, Mirjana

    2016-02-29

    The purpose of this study was to examine skin irritation and phototoxicity potentials of several microemulsions (ME), all comprising approximately the same percentage of surfactant mixture, but varying oil/water content and consequently inner structure being either droplet-like (o/w ME, o/w ME carbomer, w/o ME and w/o ME white wax) or lamellar (gel-like ME). Two different in vitro methods were used: MTT assay (performed either on reconstructed human epidermis (RHE) or NCTC 2544 cells) and pig ear test. Neither assay revealed the difference among ME with droplet-like structure. Then again, pig ear test and MTT assay performed on RHE indicated that gel-like ME is more irritant compared to other tested ME, whereas no difference among formulations were observed by MTT assay on NCTC 2544 cells. The reasonable explanation is destruction and consequently uniform structure of ME upon dilution that is inevitable for testing on cell cultures. The results of phototoxicity test again indicated the increased potential of gel-like ME to cause adverse effects on skin. It can be concluded that for ME consisting of the same amount of identical surfactants but having different structure the latter represent a crucial factor that determines their dermal toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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.

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

    PubMed

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

    2015-08-15

    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(+) MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical 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(-)/CD14(+)/CD68(+) 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.

  9. Crude 4-methylcyclohexanemethanol (MCHM) did not cause skin irritation in humans in 48-h patch test.

    PubMed

    Monnot, Andrew D; Novick, Rachel M; Paustenbach, Dennis J

    2017-03-13

    Crude 4-methylcyclohexanemethanol (MCHM) is an industrial chemical used to wash and clean coal. On January 9th, 2014 approximately 10,000 gallons of a mixture containing crude MCHM were released into the Elk River near Charleston, West Virginia, contaminating the local water supply. Following the spill, residents reported numerous health complaints, and sought medical attention for ailments including rashes and itching. The relationship between the complaints and the spill were unknown, as such symptoms are reported frequently in the background. In this study, the primary irritation potential of crude MCHM was evaluated in 206 individuals who underwent 48 hour semi-occluded patch testing. MCHM concentrations assessed in this study were 1, 5, 15, and 100 ppm. No appreciable skin reactions were observed in individuals at any concentration. Three of the five concentrations evaluated were above the highest measured concentration of MCHM in the tap water of residents in West Virginia (3.7 ppm). The results of this study suggest that crude MCHM would not be a dermal irritant for the vast majority, if not all, potentially exposed persons at the concentrations in the water reported after the spill.

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

    SciTech Connect

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

    2015-08-15

    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. Topical 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.

  11. [Diseases caused by diisocyanates. 1. Irritation of the respiratory system and skin].

    PubMed

    Lubach, D

    1978-01-01

    Toluylene diisocyanate (TDI) has an uncommon importance in the production of irritation of respiratory system. In the last few years less volatile isocyanate compounds have been substituted for TDI. Commercial available diphenylmethane diisocyanate (MDI) and polymethylene polyphenyl isocyanate (PAPI) were analyzed in 1971. The analysis indicated the presence of 21% TDI in several samples. It is evident, with respect to the relatively high vapor pressure of TDI, that such impurities will be able to cause air concentrations in excess of the current threshold limit value (TLV) of 0.02 ppm. Liberation of TDI by heat from varnish insulinations is a difficult problem. This problem was described as "an old hazard in new guise". Especially, in a soldering process on polyurethane coated wire, excess of TLV is possible in unfavourable conditions. By the regulation that the concentration of TLV must not exceed 0.02 ppm and by the use of new non-volatile isocyanate the risk of acute and subacute intoxications has considerably subsided. Chronic irritations of respiratory system and asthma-like diseases, however represent still an unsolved problem.

  12. [Acute pneumonias in those working with chemical substances that irritate the respiratory tract].

    PubMed

    Vladyko, N V

    1991-01-01

    A study was performed of acute pneumonia (AP) morbidity among the workers exposed to respiratory irritation inducing chemical substances, which revealed a marked AP prevalence in these professional groups. A qualitative analysis of the AP cases severity helped to establish some peculiarities of the disease course in workers exposed to minor concentrations of the chemical substances, which should be taken into account in diagnosis, prognosis, treatment and out-patient observation.

  13. Cumulative irritation potential of metronidazole gel compared to azelaic acid gel after repeated applications to healthy skin.

    PubMed

    Ziel, Kristin; Yelverton, Christopher B; Balkrishnan, Rajesh; Feldman, Steven R

    2005-01-01

    Metronidazole 0.75% gel and azelaic acid 15% gel are commonly used to treat rosacea. Irritation is a common side effect. To assess the cumulative irritation potential of metronidazole 0.75% gel and azelaic acid 15% gel. Metronidazole 0.75% gel, azelaic acid 15% gel, and a white petrolatum negative control were applied under occlusive conditions to the upper back of a total of 33 healthy subjects. There were twelve 24-hour applications (4 times a week) and three 72-hour applications on weekends during a 3-week period. Skin reactions (erythema score +/- other local reaction) were assessed within 15 to 30 minutes of removal of the products. The mean cumulative irritancy index of metronidazole 0.75% gel was significantly lower than that of azelaic acid 15% gel and not significantly higher than the negative control product. There was increasing cumulative irritancy with azelaic acid; no cumulative irritancy was seen for either metronidazole or white petrolatum. Metronidazole 0.75% gel is less irritating in sustained use than azelaic acid 15% gel.

  14. IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed; Mahmood, Asif; Sarfraz, Rai Muhammad

    2016-01-01

    The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit.

  15. Skin targeting of curcumin solid lipid nanoparticles-engrossed topical gel for the treatment of pigmentation and irritant contact dermatitis.

    PubMed

    Shrotriya, Shilpa; Ranpise, Nisharani; Satpute, Pournima; Vidhate, Bhagvat

    2017-09-08

    Irritant contact dermatitis (ICD) and hyperpigmentation are the problems associated with skin. Topical curcumin (CUR) although effective in hyperpigmentation and ICD, is a challenging molecule due to low-solubility. Encapsulation of CUR into solid lipid nanoparticles (SLNs) makes it amenable to topical dosing as their small size promotes its penetration into the skin. CUR-SLNs were prepared using Precirol ATO5 and Tween-80 by probe ultrasonication method. Further, CUR-SLNs were incorporated into Carbopol gel and investigated for ex-vivo skin permeation, skin deposition and skin irritation studies. The potential of CUR-SLN gel was checked against hyperpigmentation through the inhibition of tyrosinase enzyme. It was further evaluated for possible effects on ICD using BALB/c mice. The optimized CUR-SLN showed the particle size of 51 nm and 93% EE. Ex vivo permeation of CUR-SLN gel exhibited controlled drug release up to 24 h, similarly in vitro drug deposition studies showed potential for skin targeting. In vitro tyrosinase inhibition assay indicates that the formulated gel has potential in skin depigmentation. The gel also confirmed proficient suppression of ear swelling and reduction in skin water content in the BALB/c mouse. Thus, the CUR-SLN gel would be a safe and effective alternative to conventional vehicles for treatment of ICD and pigmentation.

  16. Self-reported skin rash or irritation symptoms among World Trade Center Health Registry participants.

    PubMed

    Huang, Monica J; Li, Jiehui; Liff, Jonathan M; Cohen, David E; Cone, James

    2012-04-01

    We described self-reported skin rash 2 to 3 and 5 to 6 years after 9/11 and examined its association with exposures to 9/11 dust/debris. We analyzed a longitudinal study of New York City World Trade Center Health Registry participants who resided or worked in Lower Manhattan or worked in rescue/recovery in two surveys (W1 and W2). Among 42,025 participants, 12% reported post-9/11 skin rash at W1, 6% both times, 16% at W2. Among participants without posttraumatic stress disorder or psychological distress, W1 self-reported post-9/11 skin rash was associated with intense dust cloud exposure (adjusted odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.3 to 1.9), home/workplace damage (adjusted OR = 1.8; 95% CI, 1.4 to 2.3), and working more than 90 days (adjusted OR = 1.7; 95% CI, 1.3 to 2.2) or 31 to 90 days (adjusted OR = 1.6; 95% CI, 1.3 to 2.1) at the World Trade Center site. Post-9/11 skin rash may be related to acute and long-term exposure to dust, though subjectivity of skin symptoms may bias findings.

  17. Irritant and sensitizing potential of eight surfactants commonly used in skin cleansers: an evaluation of 105 patients.

    PubMed

    Corazza, Monica; Lauriola, Maria Michela; Bianchi, Anna; Zappaterra, Mario; Virgili, Annarosa

    2010-01-01

    Irritation from surfactants contained in detergents is a frequent adverse reaction to cosmetics. Sensitization to surfactants is also possible. In the literature, comparative studies about irritant and sensitizing potential of different surfactants are heterogeneous and inconclusive about the best molecules to use. We compared the irritant and sensitizing potential of some surfactants that are usual components in marketed synthetic detergents (syndets) to obtain practical information regarding commonly used detergents. We patch-tested eight surfactants of the different types (anionic, cationic, amphoteric, and non-ionic) in 105 patients. Assessment of allergic reactions of tested surfactants was carried out in accordance with the recommendations of the International Contact Dermatitis Research Group; assessment of irritant power followed the amended Draize classification. None of the eight surfactants in our series gave positive allergic reactions. Only cocamidopropyl betaine from the Italian standard (Società Italiana di Dermatologia Allergologica, Professionale e Ambientale [SIDAPA]) series gave five positive reactions among 105 patients. None of the eight studied surfactants induced skin irritation. The most tolerated are two new mild anionics (sodium cocoyl glutamate and sodium lauroyl oat amino acids) and an amphoteric agent (disodium cocoamphodiacetate). From this study, we deduce that cosmetic companies' efforts to search for and market new products with very mild surfactants have been generally successful.

  18. Skin infiltration in acute promyelocytic leukemia.

    PubMed

    Nagao, K; Kikuchi, A; Kawai, Y; Kizaki, M; Ikeda, Y; Nishikawa, T

    1997-01-01

    Acute promyelocytic leukemia (APL) is a type of acute leukemia showing unique clinical, morphological and cytogenetic features. A skin infiltration by APL cells is an extremely rare occasion, but there have been several case reports of leukemia cutis in APL, in which all-trans retinoic acid (ATRA) may have induced the skin infiltration. However, no immunohistochemical analyses of the APL cells in the skin have been done to date. A 30-year-old woman with APL developed multiple reddish purple nodules on the extremities in her second complete remission. Histological findings revealed a dense infiltration of medium to large atypical cells, which were positive for myeloperoxidase, throughout the dermis. Despite the conventional chemotherapy and ATRA therapy she died from disseminated intravascular coagulation during her third relapse. Leukemic cells in the peripheral blood before the treatment with ATRA revealed CD3-/CD4-/CD5-/CD7-/CD8-/CD10-/CD13++/CD14-/CD19 -/ CD20-/CD33++/CD38++/CD41-/Ia-, but they expressed CD3-/CD4-/CD5-/CD7++/ CD8-/CD10-/CD13++/CD14-/CD19-/CD20-/CD33++ /CD38++/CD41+/Ia+ after the treatment. We suggest that the alternation of the surface molecules on the tumor cells is closely associated with the skin infiltration of APL cells.

  19. Leiden reconstructed human epidermal model as a tool for the evaluation of the skin corrosion and irritation potential according to the ECVAM guidelines.

    PubMed

    El Ghalbzouri, A; Siamari, R; Willemze, R; Ponec, M

    2008-08-01

    In the ECVAM validation studies two common skin protocols have been developed, the skin corrosion and skin irritation protocol. Both protocols include next to general and functional conditions that the skin model must meet, also the correct prediction of the activity of certain reference chemicals. For the skin corrosion protocol, the OECD TG 431 defined 12 reference chemicals that should be correctly predicted by the epidermal skin model. For skin irritation 20 test substances should meet the defined criteria. In this study we aimed to subject our Leiden human epidermal (LHE) model to both common protocols according to the ECVAM guidelines. The LHE model generated in this study has been fully characterized and shows very high similarities with the native skin. After minor technical changes in both protocols, corrosion classifications were obtained in concordance with those reported for the validated human skin models EpiSkin and EpiDerm. The results obtained with the common skin irritation protocol were very similar to that of earlier studies with the SkinEthic, EpiSkin and EpiDerm models. This means that the protocols and prediction models developed during the validation studies with a specific skin model can be used with other similar skin models. This study demonstrates that reconstructed human skin equivalents have been proven to be efficient and reliable alternatives to animal testing.

  20. Skin irritation to glass wool or continuous glass filaments as observed by a patch test among human Japanese volunteers.

    PubMed

    Tsunoda, Masashi; Kido, Takamasa; Mogi, Sachiyo; Sugiura, Yumiko; Miyajima, Eriko; Kudo, Yuichiro; Kumazawa, Tatenao; Aizawa, Yoshiharu

    2014-01-01

    Glass wool and continuous glass filaments have been used in industry. We examined the irritability of those among Japanese. A patch test was performed on 43 volunteers for the followings: glass wool for non-residential use with and without a urea-modified phenolic resin binder, that for residential use with and without the binder, and continuous glass filaments with diameters of 4, 7, 9, and 13 µm. Materials were applied to an upper arm of each volunteer for 24 h. The skin was observed at 1 and 24 h after the removal. At 1 h after removal, slight erythema was observed on the skin of a woman after the exposure to glass wool for residential use without the binder. Erythema was observed on the skin of another woman at 1 h after a 24-h exposure to glass wool for non-residential use without the binder. There were no reactions at 24 h after the removal. The low reactions in the patch test suggested that the irritability caused by glass wool, irrespective of a resin component, could be induced mechanically, and that the irritability caused by continuous glass filaments with resin could be slight and either mechanical or chemical.

  1. Skin Irritation to Glass Wool or Continuous Glass Filaments as Observed by a Patch Test among Human Japanese Volunteers

    PubMed Central

    TSUNODA, Masashi; KIDO, Takamasa; MOGI, Sachiyo; SUGIURA, Yumiko; MIYAJIMA, Eriko; KUDO, Yuichiro; KUMAZAWA, Tatenao; AIZAWA, Yoshiharu

    2014-01-01

    Glass wool and continuous glass filaments have been used in industry. We examined the irritability of those among Japanese. A patch test was performed on 43 volunteers for the followings: glass wool for non-residential use with and without a urea-modified phenolic resin binder, that for residential use with and without the binder, and continuous glass filaments with diameters of 4, 7, 9, and 13 µm. Materials were applied to an upper arm of each volunteer for 24 h. The skin was observed at 1 and 24 h after the removal. At 1 h after removal, slight erythema was observed on the skin of a woman after the exposure to glass wool for residential use without the binder. Erythema was observed on the skin of another woman at 1 h after a 24-h exposure to glass wool for non-residential use without the binder. There were no reactions at 24 h after the removal. The low reactions in the patch test suggested that the irritability caused by glass wool, irrespective of a resin component, could be induced mechanically, and that the irritability caused by continuous glass filaments with resin could be slight and either mechanical or chemical. PMID:25070402

  2. Relationship between the amount of propranolol permeating through the stratum corneum of guinea pig skin after application of propranolol adhesive patches and skin irritation.

    PubMed

    Kobayashi, I; Hosaka, K; Ueno, T; Maruo, H; Kamiyama, M; Konno, C; Gemba, M

    1996-06-01

    In the present study we evaluated the relationship between the cumulative amount of propranolol permeating through the stratum corneum and the formation of erythema, a skin irritation reaction, after transdermal application of adhesive patches containing propranolol to the skin of guinea pigs. The intensity of erythema was expressed in terms of a* values measured with a chromameter. The a* values increased in guinea pigs after application of the adhesive patches containing 0.4 mg/cm2 of propranolol to the skin. Since the adhesive patches showed good adhesion to the skin (propranolol content is less than the saturated concentration in the adhesive base) and the cumulative amount of propranolol permeating through the stratum corneum is small, the development of erythema was considered to be mainly due to physical factors such as peeling. Even in adhesive patches containing 0.8 mg/cm2 or 1.2 mg/cm2 of propranolol, a* values increased, although adhesion to the skin is low because of crystallization of propranolol in the adhesive base. On the other hand, in these two adhesive patches, the cumulative amount of propranolol permeating through the stratum corneum increased up to 24 h after application. These findings suggest that the skin irritation reaction is due to propranolol mainly absorbed transdermally, because there is a high correlation between the cumulative amount of propranolol permeating through the stratum corneum and the a* values (r = 0.928).

  3. A drug-in-adhesive matrix based on thermoplastic elastomer: evaluation of percutaneous absorption, adhesion, and skin irritation.

    PubMed

    Wang, ChengXiao; Liu, Ran; Tang, XiuZhen; Han, Wei

    2012-12-01

    A novel drug-in-adhesive matrix was designed and prepared. A thermoplastic elastomer, styrene-isoprene-styrene (SIS) block copolymer, in combination with tackifying resin and plasticizer, was employed to compose the matrix. Capsaicin was selected as the model drug. The drug percutaneous absorption, adhesion properties, and skin irritation were investigated. The results suggested that the diffusion through SIS matrix was the rate-limiting step of capsaicin percutaneous absorption. [SI] content in SIS and SIS proportions put important effects on drug penetration and adhesion properties. The chemical enhancers had strong interactions with the matrix and gave small effect on enhancement of drug skin permeation. The in vivo absorption of samples showed low drug plasma peaks and a steady and constant plasma level for a long period. These results suggested that the possible side effects of drug were attenuated, and the pharmacological effects were enhanced with an extended therapeutic period after application of SIS matrix. The significant differences in pharmacokinetic parameters produced by different formulations demonstrated the influences of SIS copolymer on drug penetrability. Furthermore, the result of skin toxicity test showed that no skin irritation occurred in guinea pig skin after transdermal administration of formulations.

  4. 78 FR 63220 - Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Acute Bacterial Skin and Skin... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... drugs to treat acute bacterial skin and skin structure infections (ABSSSI). This guidance finalizes the...

  5. Topical antioxidants protect the skin from chemical-induced irritation in the repetitive washing test: a placebo-controlled, double-blind study.

    PubMed

    Schempp, Christoph M; Meinke, Martina C; Lademann, Jürgen; Ferrari, Yvonne; Brecht, Thomas; Gehring, Wolfgang

    2012-10-01

    There is increasing evidence that reactive oxygen species play an important role in the development of both irritant and allergic contact dermatitis. To assess the potential of topical antioxidants to prevent the development of experimentally induced irritant contact dermatitis. We evaluated the effect of a cream containing a combination of antioxidants on sodium lauryl sulfate-induced irritant contact dermatitis in the repetitive washing test. As readout parameters for skin barrier function and cutaneous inflammation stratum corneum hydration, cutaneous blood flow and transepidermal water loss were assessed in 25 volunteers with bioengineering methods. In comparison with the cream base and a frequently used barrier cream, the antioxidant cream had high radical scavenging activity and effectively protected the skin from chemical-induced irritation. The superiority of the cream with antioxidants to the cream base suggests that reactive oxygen species, at least in part, play a role in the development of irritant contact dermatitis. © 2012 John Wiley & Sons A/S.

  6. Optimisation of the EpiDerm test protocol for the upcoming ECVAM validation study on in vitro skin irritation tests.

    PubMed

    Kandárová, Helena; Liebsch, Manfred; Genschow, Elke; Gerner, Ingrid; Traue, Dieter; Slawik, Birgitta; Spielmann, Horst

    2004-01-01

    An ECVAM-funded prevalidation study (PV) was conducted during 1999 and 2000 to identify in vitro tests capable of reliably distinguishing between skin irritants (I) and non-irritants (NI) according to European Union risk phrases ("R38" or no classification). The tests evaluated were EpiDerm, EPISKIN, PREDISKIN, the non-perfused pig ear method, and the mouse skin integrity function test (SIFT). Whereas reproducibility of the two human skin model tests and SIFT was acceptable, none of the methods was deemed ready to enter a formal validation study due to their low predictivity. The ECVAM Skin Irritation Task Force therefore suggested improvements of protocols and prediction models for these tests. Furthermore, it was agreed that experience gained with the two human-skin models be shared, and a common protocol should be developed for EpiDerm and EPISKIN (Zuang et al., 2002). When we applied an improved EPISKIN protocol (Portes et al., 2002) to the EpiDerm model, an acceptable specificity (80%) was achieved, whereas the sensitivity (60%) was far too low. In 2003, the EPISKIN protocol was further refined by extension of the post-incubation period following chemical exposure. In the current study, we evaluated this EPISKIN refinement by applying it to EpiDerm. In addition, we developed technical improvements for the application of the test chemicals and rinsing procedure, which reduced the variability of results and increased the percentage of correct predictions. A set of twenty non-coded reference substances from the ECVAM prevalidation study phase III (Fentem et al., 2001) was tested with the final protocol in three independent runs. Both high sensitivity (80%) and high specificity (78%) were achieved, and the statistical probability of correct classifications was high, so that the test is now regarded ready for formal validation.

  7. Phospholipidomic Profile Variation on THP-1 Cells Exposed to Skin or Respiratory Sensitizers and Respiratory Irritant.

    PubMed

    Martins, João D; Maciel, Elisabete A; Silva, Ana; Ferreira, Isabel; Ricardo, Fernando; Domingues, Pedro; Neves, Bruno M; Domingues, Maria Rosário M; Cruz, Maria Teresa

    2016-12-01

    Occupational exposure to low molecular weight reactive chemicals often leads to development of allergic reactions such as allergic contact dermatitis and respiratory allergies. Further insights into the interaction of these chemicals with physiopathological relevant cellular models might provide the foundations for novel non-animal approaches to safety assessment. In this work we used the human THP-1 cell line to determine phospholipidome changes induced by the skin sensitizer 1-fluoro-2,4-dinitrobenzene (DNFB), the respiratory allergen hexamethylene diisocyanate (HDI), and the irritant methyl salicylate (MESA). We detected that these chemicals differently induce lipid peroxidation and modulate THP-1 IL-1β, IL-12B, IL-8, CD86, and HMOX1 transcription. Decreased phosphatidylethanolamine content was detected in cells exposed to MESA, while profound alterations in the relative abundance of cardiolipin species were observed in cells exposed to DNFB. All chemicals tested induced a decrease in the relative abundance of plasmanyl phosphatidylcholine species PC (O-16:0e/18:1) and phosphatidylinositol species PI (34:1), while increasing PI (38:4). An increased abundance of oleic acid was observed in the phospholipids of cells exposed to DNFB while a decreased abundance of palmitic acid was detected in cells treated with MESA or DNFB. We conclude that both specific and common alterations at phospholipidome levels are triggered by the different chemicals, while not allowing a complete distinction between them using a Canonical Analysis of Principal Coordinates (CAP). The common effects observed at phospholipids level with all the chemicals tested might be related to unspecific cell cytotoxic mechanisms that nevertheless may contribute to the elicitation of specific immune responses. J. Cell. Physiol. 231: 2639-2651, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Prostanoid receptors and acute inflammation in skin.

    PubMed

    Hohjoh, Hirofumi; Inazumi, Tomoaki; Tsuchiya, Soken; Sugimoto, Yukihiko

    2014-12-01

    Prostanoids such as prostaglandins (PGs) and thromboxanes exert a wide variety of actions via nine types of G protein-coupled receptors, including four PGE2 receptors (EPs) and two PGD2 receptors (DPs). Recent studies have revealed that prostanoids trigger or modulate acute inflammation in the skin via multiple mechanisms involving distinct receptors and molecules; PGE2 elicits vascular permeability and edema formation via EP3 receptor on mast cells, and PGE2 increases blood flow by eliciting vasodilatation via EP2/EP4 receptors on smooth muscle cells. PGD2-DP1 signaling plays a role in mast cell maturation and mast cell-mediated inflammation. Therefore, the local inhibition of specific prostanoid receptor signaling is expected to be an effective strategy for the prevention and treatment of acute inflammation.

  9. Enhancement of visual scoring of skin irritant reactions using cross-polarized light and parallel-polarized light.

    PubMed

    Farage, Miranda A

    2008-03-01

    Polarized light has been used as an aid in visualizing various skin conditions, including acne vulgaris, rosacea, photoageing, lentigo simplex, and basal cell carcinoma. The use of parallel-polarized and cross-polarized light was evaluated in mild irritant reactions to determine, if this increases the ability to detect very early stages or low levels of irritation. Low concentrations of sodium lauryl sulfate (0.01% and 0.1%) were patched on human volunteers for 2, 6, and 24 hr, daily for 2-3 days in a modification of the standard patch test. Feminine protection products were evaluated in the behind-the-knee (BTK) test. Erythema reactions were scored by unaided visual assessment and using a polarized light visualization system. In the 24-hr patch test, mean erythema assessed with polarized light was consistent with results of unaided visual scoring. Under milder conditions (2- and 6-hr patches), and in the BTK, significant differences from pretreatment levels of erythema were apparent earlier in the series of treatments compared with unaided scoring. In addition, subsurface scoring demonstrated that changes were still present under the skin surface even after unaided visual scoring indicated recovery. Low (subclinical) levels of irritation can be detected using enhanced visual scoring, indicating this non-invasive method has the potential to increase the sensitivity of our clinical studies.

  10. Evaluation of existing (Q)SAR models for skin and eye irritation and corrosion to use for REACH registration.

    PubMed

    Verheyen, Geert R; Braeken, Els; Van Deun, Koen; Van Miert, Sabine

    2017-01-04

    The performance of the (Q)SAR models Derek Nexus, Toxtree and Case Ultra for the prediction of skin and eye irritation/corrosion is investigated. For irritation and corrosion of the skin, 117 compounds and for the eye, 125 compounds were listed. The balance between the groups positive and negative for irritation and corrosion was maintained. The obtained predictions were compared with experimental data and the numbers of true and false positives and negatives were determined. Based on these results several performance parameters of the tested (Q)SAR models were calculated. Despite all the efforts to make good and valid models, the results indicate a poor predictivity of the current models: a lot of compounds were not predicted, were out of the applicability domain or were predicted wrong. Considering our results, it can be concluded that the tested models are not yet sufficiently powerful for implementation. Possibly the training-sets used within the current models are not yet comprehensive enough or the incorporated data are not of enough quality. Although the use of these models as stand-alone evaluation is not recommended, these models can be of value as weight-of-evidence in the context of expert knowledge in an Integrated Approach to Testing and Assessment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Targeted delivery of salicylic acid from acne treatment products into and through skin: role of solution and ingredient properties and relationships to irritation.

    PubMed

    Rhein, Linda; Chaudhuri, Bhaskar; Jivani, Nur; Fares, Hani; Davis, Adrian

    2004-01-01

    Salicylic acid (SA) is a beta hydroxy acid and has multifunctional uses in the treatment of various diseases in skin such as acne, psoriasis, and photoaging. One problem often cited as associated with salicylic acid is that it can be quite irritating at pH 3-4, where it exhibits the highest activity in the treatment of skin diseases. We have identified strategies to control the irritation potential of salicylic acid formulations and have focused on hydroalcoholic solutions used in acne wipes. One strategy is to control the penetration of SA into the skin. Penetration of the drug into various layers of skin, i.e., epidermis, dermis, and receptor fluid, was measured using a modified Franz in vitro diffusion method after various exposure times up to 24 hours. A polyurethane polymer (polyolprepolymer-15) was found to be an effective agent in controlling delivery of SA. In a dose-dependent fashion it targeted delivery of more SA to the epidermis as compared to penetration through the skin into the receptor fluid. It also reduced the rapid rate of permeation of a large dose of SA through the skin in the first few hours of exposure. A second strategy that proved successful was incorporation of known mild nonionic surfactants like isoceteth-20. These surfactants cleanse the skin, yet due to their inherent mildness (because of their reduced critical micelle concentration and monomer concentration), keep the barrier intact. Also, they reduce the rate of salicylic acid penetration, presumably through micellar entrapment (either in solution or on the skin surface after the alcohol evaporates). Cumulative irritation studies showed that targeting delivery of SA to the epidermis and reducing the rapid early rate of penetration of large amounts of drug through the skin resulted in a reduced irritation potential. In vivo irritation studies also showed that the surfactant system is the most important factor controlling irritancy. SA delivery is secondary, as formulations with less

  12. Pharmacokinetic Manipulation and Modeling of the Trigger for JP-8-Induced Skin Irritation

    DTIC Science & Technology

    2009-01-30

    with identical exposures to octane (a minor component of JP-8) and cumene (an irritant) (McDougal et al., in preparation). Table 4 shows that the...magnitude of gene expression changes due to JP-8 was about 6-fold less than that of octane and cumene . Visual observations and histological analysis of...metabolism for cumene . In addition, Table 5 shows the relative magnitude (fold- change) of changes for representative genes related to irritation for JP-8

  13. Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome.

    PubMed

    Thoua, N M; Murray, C D R; Winchester, W J; Roy, A J; Pitcher, M C L; Kamm, M A; Emmanuel, A V

    2009-03-01

    Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response. To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients. Nineteen patients with IBS were given amitriptyline 25-50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity). Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders (P > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline -31% vs. +2%, P < 0.03 respectively). In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.

  14. Acute effects of UVR on human eyes and skin.

    PubMed

    Young, Antony R

    2006-09-01

    Solar UVR ( approximately 295-400 nm) has acute clinical effects on the eyes and the skin. The only effect on the eye is inflammation of the cornea (photokeratitis), which is caused by UVB (and non-solar UVC) and resolves without long-term consequences within 48 h. The effects on the skin are more extensive and include sunburn (inflammation), tanning and immunosuppression for which UVB is mainly responsible. Tanning is modestly photoprotective against further acute UVR damage. Skin colour is also transiently changed by UVA-dependent immediate pigment darkening, the function of which is unknown. Skin type determines sensitivity to the acute and chronic effects of UVR on the skin. Some of the photochemical events that initiate acute effects are also related to skin cancer. Solar UVB is also responsible for the synthesis of vitamin D.

  15. 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.

  16. 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

    2017-03-06

    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.

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

    PubMed

    Mewes, K R; Fischer, A; Zöller, N N; Laubach, V; Bernd, A; Jacobs, A; van Rompay, A; Liebsch, M; Pirow, R; Petersohn, D

    2016-10-01

    We have developed a new in vitro skin irritation test based on an open source reconstructed epidermis (OS-REp) with openly accessible protocols for tissue production and test performance. Due to structural, mechanistic and procedural similarity, a blinded catch-up validation study for skin irritation according to OECD Performance Standards (PS) was conducted in three laboratories to promote regulatory acceptance, with OS-REp models produced at a single production site only. While overall sensitivity and predictive capacity met the PS requirements, overall specificity was only 57%. A thorough analysis of the test results led to the assumption that some of the false-positive classifications could have been evoked by volatile skin-irritating chemicals tested in the same culture plate as the non-irritants falsely predicted as irritants. With GC/MS and biological approaches the cross-contamination effect was confirmed and the experimental set-up adapted accordingly. Retesting of the affected chemicals with the improved experimental set-up and otherwise identical protocol resulted in correct classifications as non-irritants. Taking these re-test results into account, 93% overall sensitivity, 70% specificity and 82% accuracy was achieved, which is in accordance with the OECD PS. A sufficient reliability of the method was indicated by a within-laboratory-reproducibility of 85-95% and a between-laboratory-reproducibility of 90%. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. 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.

  19. Assessment of the in vitro dermal irritation potential of cerium, silver, and titanium nanoparticles in a human skin equivalent model.

    PubMed

    Miyani, Vivek A; Hughes, Michael F

    2017-06-01

    Metal nanoparticles can potentially contact human skin during their manufacture and use in commercial products. This study examined the potential of metal nanoparticles to elicit irritant contact dermatitis in a human skin equivalent model (HSEM) derived from keratinocytes. Ag (10-100 nm), TiO2 (22-214 nm), and CeO2 (15-40 nm) nanoparticles were studied. The Ag particles were either coated/shelled with silica or capped with citrate or polyvinylpyrrolidone and were in water. The TiO2 and CeO2 particles were suspended in media containing 10% fetal bovine serum. The particles (1 mg/ml) were applied to the epidermal surface of the HSEM. Positive (5% sodium dodecyl sulfate (SDS)) and negative controls (saline or media) were included. After 1-h exposure at 37 °C, the HSEM was washed with saline to remove the nanoparticles. Following a 42-h incubation (37 °C), HSEM viability was assessed using the MTT assay. A test substance is considered a dermal irritant if the HSEM viability is < 50%. The mean viability for the SDS-treated HSEM was 7.8%. The viabilities of the nanoparticle-treated HSEM were 91% or greater. The Ag, TiO2, and CeO2 nanoparticles examined were not dermal irritants under the conditions used in this study. The stratum corneum of the HSEM may limit penetration of metal nanoparticles to induce toxicity.

  20. 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.

  1. Acute tryptophan depletion reduces kynurenine levels: implications for treatment of impaired visuospatial memory performance in irritable bowel syndrome.

    PubMed

    Kennedy, Paul J; Allen, Andrew P; O'Neill, Ann; Quigley, Eamonn M M; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2015-04-01

    A visuospatial episodic memory impairment has recently been identified in irritable bowel syndrome. Increased tryptophan metabolism along the kynurenine pathway has also been reported in irritable bowel syndrome, which may play a role in altered cognitive performance as peripheral kynurenine can cross the blood brain barrier and lead to the production of neuroactive metabolites, which modulate glutamatergic and cholinergic signalling, key neurotransmitter systems involved in cognitive function. Utilising the acute tryptophan depletion (ATD) protocol, the aim of this study was to examine if manipulating peripheral levels of tryptophan regulates cognitive performance in irritable bowel syndrome and also to determine for the first time if the ATD protocol alters kynurenine supply to the central nervous system. In this double-blind, placebo-controlled, crossover design study, nine female patients with irritable bowel syndrome and 14 matched female healthy controls participant completed a range of tests from the CANTAB(®) following ATD and placebo. Plasma tryptophan and kynurenine, self-report measures of gastrointestinal symptoms, mood and arousal were determined pre- and post-treatment on each study day. Following placebo (p = 0.016) but not ATD (p > 0.05), patients with irritable bowel syndrome exhibited impaired visuospatial memory performance (Paired Associates Learning (PAL) test). In addition, ATD significantly decreased (p < 0.001) and placebo significantly increased (p < 0.001) plasma kynurenine levels in both groups. Manipulating peripheral tryptophan and kynurenine levels using ATD modulates hippocampal-mediated cognitive performance in irritable bowel syndrome but not healthy controls. These data may have important implications for reducing cognitive impairment in irritable bowel syndrome.

  2. The EpiDerm test protocol for the upcoming ECVAM validation study on in vitro skin irritation tests--an assessment of the performance of the optimised test.

    PubMed

    Kandárová, Helena; Liebsch, Manfred; Gerner, Ingrid; Schmidt, Elisabeth; Genschow, Elke; Traue, Dieter; Spielmann, Horst

    2005-08-01

    During the past decade, several validation studies have been conducted on in vitro methods for discriminating between skin irritating and non-irritating chemicals. The reconstructed human skin models, EpiDerm and EPISKIN, provided the most promising results. Based on experience of the similar performance of the two skin models, it was suggested that a common test protocol and prediction model should be developed for the prediction of skin irritation potential with the two models. When the EPISKIN protocol was applied with the EpiDerm model, an acceptable specificity (80%) was achieved, whereas the sensitivity (60%) was low. In 2003, the EPISKIN protocol was further refined by extending the post-incubation period following exposure to test chemicals. This extension and additional technical improvements to the EpiDerm protocol were evaluated with 19 chemicals from the prevalidation study. With the new test design, high sensitivity (80%) and specificity (78%) were obtained. The statistical probability for correct classifications was high, so the test was considered to be ready for formal validation. However, since test optimisation had been conducted with the same test chemicals as were used in the ECVAM prevalidation study, it was decided that the optimisation of the protocol had to be verified with a new set of chemicals. Thus, in the current study, 26 additional chemicals (10 rabbit irritants and 16 non-irritants), which had previously been selected and tested by LOREAL with EPISKIN, were evaluated in three independent experiments with EpiDerm. With this unbalanced testing set, a specificity of 94%, and a sensitivity of 60% were obtained, while the positive and negative predictivity and accuracy remained almost unchanged (around 80%) in comparison to the in vivo rabbit data. Overall, 45 chemicals (20 irritants and 25 non-irritants) were tested according to the final protocol. The resulting high positive (82%) and negative predictive values (79%) confirmed the

  3. [Irritative effect of aclacinomycin A on the eye mucous membrane, skin and muscle (author's transl)].

    PubMed

    Ohmori, K; Hirano, S; Kiyosaki, T; Hori, S; Tone, H

    1980-04-01

    Aclacinomycin A, a new anthracycline antitumor antibiotic, was given to rabbits by single instillation or single intracutaneous injection and to guinea pigs by single subcutaneous or intramuscular injection to examine the irritative effect. Slight dilatation of blood vessel and swelling in the conjunctiva and nictitating membrane were observed in the eyes of rabbits given 1% solution. Edema in the bulbar conjunctiva, iris and cornea was histologically noted. Washing of the eyes after drug instillation prevented these damages. Subcutaneous and intracutaneous injections of 1% solution (0.2 ml) gave hyperemia, swelling and necrosis at injection site. Cellular infiltration, fibrosis and necrosis were histologically detected. Intramuscular injection of 1% solution (0.2 ml) also provided induration and swelling at injection site. Histologically cellular infiltration and necrosis were observed. These irritative effects were much slighter in administration of 0.1% solution. No change was observed with 0.01% solution.

  4. 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.

  5. 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.

  6. 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.

  7. Acute toxicity and irritation of water-based dextran-coated magnetic fluid injected in mice.

    PubMed

    Yu, Zhai; Xiaoliang, Wang; Xuman, Wang; Hong, Xie; Hongchen, Gu

    2008-06-01

    Based on the elements that magnetic nanoparticles could heat in an alternating magnetic field, magnetic fluid hyperthermia occurred to inhibit tumor growth in vivo. However, biocompatibility of those fluids as well as the fluid-body interaction remains unclear. In this article, acute toxicity and irritation of the water-based dextran-coated magnetic fluid (dextran-magnetic fluid) injected into mice subcutaneous tissues were examined. Lethal dosage 50 of single treatment with the magnetic fluid was 4409.61 +/- 514.93 mg/kg. When injected with 30 mg/0.3 mL dextran-magnetic fluid, activities of glutamicoxalacetictransaminase (AST) and glutamicpyruvictransaminase (ALT) and cell number of mice blood did not change statistically. Hemangiectasia and leucocytes infiltration were seen in subcutaneous tissues and these phenomena almost disappeared 72 h later. That is to say, the dextran-magnetic fluid was tolerable, safe, and biocompatible. The work is a basic for application of the dextran-magnetic fluid in subcutaneous tumor therapy.

  8. 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.

  9. Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: historic cohort study.

    PubMed

    Wensaas, Knut-Arne; Langeland, Nina; Hanevik, Kurt; Mørch, Kristine; Eide, Geir Egil; Rortveit, Guri

    2012-02-01

    Giardia lamblia is a common cause of gastroenteritis worldwide, but there is limited knowledge about the long-term complications. To estimate the relative risk of irritable bowel syndrome (IBS) and chronic fatigue 3 years after acute giardiasis. Controlled historic cohort study with 3 years' follow-up. Data collected by mailed questionnaire. Waterborne outbreak of giardiasis in the city of Bergen, Norway. 817 patients exposed to Giardia lamblia infection verified by detection of cysts in stool samples and 1128 matched controls. IBS and chronic fatigue. The prevalence of IBS in the exposed group was 46.1%, compared with 14.0% in the control group, and the adjusted RR=3.4 (95% CI 2.9 to 3.8). Chronic fatigue was reported by 46.1% of the exposed group and 12.0% of the controls, the adjusted RR was 4.0 (95% CI 3.5 to 4.5). IBS and chronic fatigue were associated and the RR for the exposed group of having a combination of the two outcomes was 6.8 (95% CI 5.3 to 8.5). The RR was also increased for having just one of the two syndromes, 1.8 for IBS (95% CI 1.4 to 2.3) and 2.2 for chronic fatigue (95% CI 1.7 to 2.8). Infection with Giardia lamblia in a non-endemic area was associated with a high prevalence of IBS and chronic fatigue 3 years after acute illness, and the risk was significantly higher than in the control group. This shows that the potential consequences of giardiasis are more serious than previously known. Further studies are needed, especially in areas where giardiasis is endemic.

  10. Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls.

    PubMed

    Kilkens, T O C; Honig, A; van Nieuwenhoven, M A; Riedel, W J; Brummer, R-J M

    2004-12-01

    Serotonin, a key denominator of the brain-gut axis, is involved in the regulation of gastrointestinal motility, secretion, and perception as well as cognition and mood. To assess the effects of an acutely lowered serotonin synthesis, using the acute tryptophan depletion (ATD) method, on visceral perception, affective memory performance, and mood in diarrhoea predominant irritable bowel syndrome patients (d-IBS) and controls. In a randomised, double blind, crossover design, 14 d-IBS patients and fourteen matched controls were studied under ATD and placebo conditions, respectively. Perception of urge and pain was scored during rectal distensions. Affective memory performance, mood, and biochemical parameters of serotonergic metabolism were simultaneously assessed. ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) mumol/l) and 5-hydroxyindole acetic acid concentrations (29.9 (1.0) v 15.8 (0.6) nmol/l). ATD was associated with significantly increased urge scores specifically in the lower pressure range and overall increased pain scores. ATD significantly lowered the perceptual threshold for first perception compared with placebo (patients 10.6 (1.2) v 13.6 (0.8) mm Hg, controls 12.6 (1.3) v 15.7 (1.2) mm Hg) but not for maximal tolerable discomfort (patients 50.5 (3.6) v 51.6 (3.3) mm Hg, controls 50.9 (3.3) v 48.8 (2.9) mm Hg). ATD induced a significant shift in affective memory bias towards preferential loss of positive material but no significant changes in mood. ATD did not differentially affect the patient or control group. We have provided evidence that serotonergic modulation by ATD affects both visceral perception as well as cognition in d-IBS and controls. Simultaneous measurement of brain and gut function and the application of ATD contribute to the elucidation of the complex pathophysiology of IBS.

  11. 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.

  12. 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.

  13. 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

  14. Acute disseminated candidiasis with skin lesions: a systematic review.

    PubMed

    Guarana, Mariana; Nucci, Marcio

    2017-08-25

    Neutropenic patients developing acute disseminated candidiasis may present with skin lesions. To evaluate the epidemiology of acute disseminated candidiasis with skin lesions in neutropenic patients, taking into consideration changes caused by different prophylactic strategies. A systematic review of English articles using PubMed (1963-2016) was performed. We asked the following questions: (1) What Candida species are more frequently involved in this syndrome? (2) Has antifungal prophylaxis changed the species causing skin lesions? (3) What are the typical patterns of skin lesions? (4) What is the frequency of skin lesions in neutropenic patients with candidemia or acute disseminated candidiasis? (5) Has antifungal prophylaxis decreased the incidence of acute disseminated candidiasis with skin lesions? Among 183 studies, 33 were selected, reporting 100 cases of acute disseminated candidiasis with skin lesions in neutropenic patients. It occurred more frequently in the setting of induction therapy for de novo or relapsed acute leukemia, and the most frequent species were C. tropicalis (68%) and C. krusei (15%). Diffuse maculopapular lesions predominated in cases caused by C. tropicalis and nodular and papular lesions in cases caused by C. krusei. Prophylaxis with fluconazole was reported in six cases; C. krusei in five, and C. ciferri in one. The death rate was 46.3%. Two patterns were recognized: disseminated maculopapular lesions caused by C. tropicalis in patients not receiving fluconazole prophylaxis, occurring in 39-44% of neutropenic patients with acute disseminated candidiasis, and nodular lesions caused by C. krusei in patients on fluconazole prophylaxis, occurring less frequently. Copyright © 2017. Published by Elsevier Ltd.

  15. 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

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

    2017-07-01

    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.

  16. 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

  17. 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.

  18. The effects of an acute serotonergic challenge on brain-gut responses in irritable bowel syndrome patients and controls.

    PubMed

    Kilkens, T O C; Honig, A; Fekkes, D; Brummer, R-J M

    2005-11-01

    Serotonin, a key denominator of the brain-gut axis is involved in the regulation of gastrointestinal function as well as cognition, mood and hypothalamic-pituitary-adrenal axis-mediated neuroendocrine responses. To assess the effects of an acutely increased serotonergic activity, using a 20 mg intravenous citalopram challenge test on visceral perception, affective memory performance, mood and neuroendocrine responses, respectively, in diarrhoea-predominant irritable bowel syndrome patients and controls. In a randomized, double-blind crossover design, 14 diarrhoea-predominant irritable bowel syndrome patients and 14 matched controls were studied under citalopram and placebo conditions, respectively. Visceral perception was scored in response to rectal distensions. Affective memory performance, mood, levels of adrenocorticotropic hormone, cortisol, prolactin and biochemical parameters of serotonergic metabolism were simultaneously assessed. Visceral perception did not significantly differ between the citalopram and placebo condition. Citalopram administration enhanced affective memory performance because of a bias towards positive material but no significant changes in mood. Citalopram significantly increased plasma serotonin, adrenocorticotropic hormone and cortisol levels compared with placebo. Citalopram did not differentially affect the patient or control group. We have provided evidence that acutely increased serotonergic activity influences neuroendocrine responses and cognition in diarrhoea-predominant irritable bowel syndrome and controls without a significant effect on visceral perception.

  19. Skin irritation and dryness associated with two hand-hygiene regimens: soap-and-water hand washing versus hand antisepsis with an alcoholic hand gel.

    PubMed

    Boyce, J M; Kelliher, S; Vallande, N

    2000-07-01

    To compare the frequency of skin irritation and dryness associated with using an alcoholic-hand-gel regimen for hand antisepsis versus using soap and water for hand washing. Prospective randomized trial with crossover design. Irritation and dryness of nurses' hands were evaluated by self-assessment and by visual assessment by a study nurse. Epidermal water content of the dorsal surface of nurses' hands was estimated by measuring electrical capacitance of the skin. Miriam Hospital, a 200-bed university-affiliated teaching hospital. Thirty-two nurses working on three hospital wards participated in the trial, which lasted 6 weeks. Self-assessment scores of skin irritation and dryness decreased slightly during the 2 weeks when nurses used the alcoholic-hand-gel regimen (mean baseline score, 2.72; mean final score, 2.0; P=.08) but increased substantially during the 2 weeks when nurses used soap and water (mean baseline score, 2.0; mean final score, 4.8; P<.0001). Visual assessment scores by the study nurse of skin irritation and dryness did not change significantly when the alcoholic-hand-gel regimen was used (mean baseline and final scores were both 0.55), but scores increased substantially when nurses used soap and water (baseline score, 0.59; mean final score, 1.21; P=.05). Epidermal water content of the dorsal surface of nurses' hands changed little when the alcoholic-hand-gel regimen was used (mean+/-standard deviation baseline electrical capacitance reading, 24.8+/-6.8; mean final reading, 25.7+/-7.3), but decreased significantly (skin became dryer) with soap-and-water hand washing (mean baseline, 25.9+/-7.5; mean final reading, 20.5+/-5.4; P=.0003). Hand antisepsis with an alcoholic-hand-gel regimen was well tolerated and did not result in skin irritation and dryness of nurses' hands. In contrast, skin irritation and dryness increased significantly when nurses washed their hands with the unmedicated soap product available in the hospital. Newer alcoholic hand

  20. Clinically Diagnosed Acute Diverticulitis in Outpatients: Misdiagnosis in Patients with Irritable Bowel Syndrome.

    PubMed

    Longstreth, George F; Tieu, Ryan S

    2016-02-01

    Physicians often diagnose diverticulitis and prescribe antibiotics in outpatients with abdominal pain and tenderness without other evidence. We investigated the misattribution of irritable bowel syndrome (IBS) symptoms to diverticulitis in outpatients. In patients diagnosed with diverticulitis and dispensed antibiotics in an integrated healthcare system, we retrospectively compared 15,846 outpatients managed without computed tomography (CT) versus 3750 emergency department/inpatients who had CT. We assessed demographics and past history, including 17 symptom-based somatic and 11 mental disorders and three somatic-mental comorbidity pairs (dyads) coded over 3 years and seven drug classes dispensed over 1 year before diagnosis. Univariate analysis showed small intergroup demographic differences. Outpatients had increases in prior diverticulitis, including outpatient-managed episodes, total somatic diagnoses (p < .0001), eight somatic and three mental disorders (p ≤ .015), all three dyads (p ≤ .05), and dispensing of three drug classes (p ≤ .016). IBS had been diagnosed in 2399 (15.1 %) outpatients versus 361 (9.6 %) emergency department/inpatients (p < .0001), the greatest increase in any comorbidity. Emergency department/inpatients had no somatic comorbidity more often but more alcohol dependence, non-dependent drug abuse, and opioid dispensing (p ≤ .05). Regression analysis revealed outpatient care was independently positively associated with younger age, non-Hispanic white race/ethnicity, less Charlson comorbidity, diverticulitis history, IBS, chest pain, dyspepsia, fibromyalgia, low back pain, migraine, acute reaction to stress, and antispasmodic and anxiolytic dispensing and negatively associated with non-dependent drug abuse and opioid dispensing (p ≤ .0226). Multiple types of indirect and concordant evidence suggest misattribution of IBS pain to diverticulitis and unnecessary antibiotic therapy in outpatients.

  1. Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury

    PubMed Central

    Aggarwal, Saurabh; Lam, Adam; Bolisetty, Subhashini; Carlisle, Matthew A.; Traylor, Amie; Agarwal, Anupam

    2016-01-01

    Abstract Aims: Exposure to irritant gases, such as bromine (Br2), poses an environmental and occupational hazard that results in severe lung and systemic injury. However, the mechanism(s) of Br2 toxicity and the therapeutic responses required to mitigate lung damage are not known. Previously, it was demonstrated that Br2 upregulates the heme degrading enzyme, heme oxygenase-1 (HO-1). Since heme is a major inducer of HO-1, we determined whether an increase in heme and heme-dependent oxidative injury underlies the pathogenesis of Br2 toxicity. Results: C57BL/6 mice were exposed to Br2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 μg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1−/−) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. Innovation: This is the first study delineating the role of heme in ALI caused by Br2. Conclusion: The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI. Antioxid. Redox Signal. 24, 99–112. PMID:26376667

  2. Histomorphology and Immunophenotype of Eczematous Skin Lesions Revisited-Skin Biopsies Are Not Reliable in Differentiating Allergic Contact Dermatitis, Irritant Contact Dermatitis, and Atopic Dermatitis.

    PubMed

    Frings, Verena G; Böer-Auer, Almut; Breuer, Kristine

    2017-03-10

    Lesions of allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), and atopic dermatitis (AD) share similar clinical features and thus, their diagnosis can be challenging. The aim of this study was to reassess histopathology and immunophenotyping properties to distinguish between ACD, ICD, and AD. Charts of patients with eczema, who had undergone complete routine diagnostic workup (skin biopsies, patch tests, skin prick tests, and respectively or serum IgE levels), were reviewed. Thirty-five skin biopsy specimens of 28 patients (mean age 64 ± 15 years; ♀ = 13 ♂ = 15) with clear diagnosis of ACD (n = 15), ICD (n = 6), or AD (n = 14) were analyzed. Histomorphological and immunohistochemical (CD3, CD4, CD8, CD11c, CD34, CD123, S100, and IL-17) parameters were evaluated using Kruskal-Wallis test, Wilcoxon test, Fisher exact test, and decision tree analysis. Eosinophils were statistically significant (P = 0.0184), more often observed in AD than in ACD or ICD. No other statistically significant differences were found with regard to epidermal patterns, patterns of dermal infiltrates, or immunophenotyping. Using predictive modeling approaches, dermal eosinophils were found to be associated with AD, necrotic epidermal keratinocytes with ICD, and a focal type of parakeratosis with ACD. As an additional finding, pseudo-Pautrier microabscesses, which were present in the skin of 2 AD and 2 ACD patients, contained myeloid dendritic cells (CD11c-+). Differentiation of ACD, ICD, and AD should be based on clinical features and results of allergy tests. Histopathology does not reliably differentiate between ACD, ICD, and AD, but helps to exclude psoriasis, tinea, or T-cell lymphoma.

  3. Beryllium Metal I. Experimental Results on Acute Oral Toxicity, Local Skin and Eye Effects, and Genotoxicity

    PubMed Central

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  4. Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

    PubMed

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  5. Evaluation of EpiDerm full thickness-300 (EFT-300) as an in vitro model for skin irritation: Studies on aliphatic hydrocarbons

    PubMed Central

    Mallampati, Ramya; Patlolla, Ram R.; Agarwal, Saurab; Babu, R. Jayachandra; Hayden, Patrick; Klausner, Mitchell; Singh, Mandip S.

    2010-01-01

    The aim of this study was to understand the skin irritation effects of saturated aliphatic hydrocarbons (HCs), C9–C16, found jet fuels using in vitro 3-dimensional EpiDerm full thickness-300 (EFT-300) skin cultures. The EFT-300 cultures were treated with 2.5 µl of HCs and the culture medium and skin samples were collected at 24 and 48 h to measure the release of various inflammatory biomarkers (IL-1α, IL-6 and IL-8). To validate the in vitro results, in vivo skin irritation studies were carried out in hairless rats by measuring trans epidermal water loss (TEWL) and erythema following un-occlusive dermal exposure of HCs for 72 h. The MTT tissue viability assay results with the EFT-300 tissue show that 2.5 µl/tissue (≈4.1 µl/cm2) of the HCs did not induce any significant changes in the tissue viability for exposure times up to 48 h of exposure. Microscopic observation of the EFT-300 cross-sections indicated that there were no obvious changes in the tissue morphology of the samples at 24 h, but after 48 h of exposure, tridecane, tetradecane and hexadecane produced a slight thickening and disruption of stratum corneum. Dermal exposures of C12–C16 HCs for 24 h significantly increased the expression of IL-1α in the skin as well as in the culture medium. Similarly, dermal exposure of all HCs for 24 h significantly increased the expression of interleukin-6 (IL-6) and IL-8 in the skin as well as in the culture medium in proportion to the HC chain length. As the exposure time increased to 48 h, IL-6 concentrations increased 2-fold compared to the IL-6 values at 24 h. The in vivo skin irritation data also showed that both TEWL and erythema scores increased with increased HCs chain length (C9–C16). In conclusion, the EFT-300 showed that the skin irritation profile of HCs was in the order of C9 ≤ C10 ≤ C11 ≤ C12 < C13 ≈ C14 ≈ C16 and that the tissue was an excellent in vitro model to predict in vivo irritation and to understand the structural activity

  6. Evaluation of EpiDerm full thickness-300 (EFT-300) as an in vitro model for skin irritation: studies on aliphatic hydrocarbons.

    PubMed

    Mallampati, Ramya; Patlolla, Ram R; Agarwal, Saurab; Babu, R Jayachandra; Hayden, Patrick; Klausner, Mitchell; Singh, Mandip S

    2010-03-01

    The aim of this study was to understand the skin irritation effects of saturated aliphatic hydrocarbons (HCs), C9-C16, found jet fuels using in vitro 3-dimensional EpiDerm full thickness-300 (EFT-300) skin cultures. The EFT-300 cultures were treated with 2.5microl of HCs and the culture medium and skin samples were collected at 24 and 48h to measure the release of various inflammatory biomarkers (IL-1alpha, IL-6 and IL-8). To validate the in vitro results, in vivo skin irritation studies were carried out in hairless rats by measuring trans epidermal water loss (TEWL) and erythema following un-occlusive dermal exposure of HCs for 72h. The MTT tissue viability assay results with the EFT-300 tissue show that 2.5microl/tissue ( approximately 4.1microl/cm(2)) of the HCs did not induce any significant changes in the tissue viability for exposure times up to 48h of exposure. Microscopic observation of the EFT-300 cross-sections indicated that there were no obvious changes in the tissue morphology of the samples at 24h, but after 48h of exposure, tridecane, tetradecane and hexadecane produced a slight thickening and disruption of stratum corneum. Dermal exposures of C12-C16 HCs for 24h significantly increased the expression of IL-1alpha in the skin as well as in the culture medium. Similarly, dermal exposure of all HCs for 24h significantly increased the expression of interleukin-6 (IL-6) and IL-8 in the skin as well as in the culture medium in proportion to the HC chain length. As the exposure time increased to 48h, IL-6 concentrations increased 2-fold compared to the IL-6 values at 24h. The in vivo skin irritation data also showed that both TEWL and erythema scores increased with increased HCs chain length (C9-C16). In conclusion, the EFT-300 showed that the skin irritation profile of HCs was in the order of C9C10C11C12irritation and to understand the

  7. Skin Irritation and Sensitization Potential of Fixed-Dose Combination of Diclofenac 1% and Menthol 3% Topical Gel: Results of Two Phase I Patch Studies.

    PubMed

    Liu, Dongzhou Jeffery; Collaku, Agron; Dosik, Jonathan S

    2017-02-01

    Phase I, randomized, controlled patch studies were conducted to evaluate skin sensitization and irritation potential of a new gel formulation containing 1% diclofenac and 3% menthol as a fixed-combination product.In study A, healthy volunteers were exposed to 4 test patches containing 1% diclofenac+3% menthol, diclofenac, menthol, or placebo gels during an induction (nine 48 to 72-h applications) and challenge phase (one 48-h application). Some subjects were re-challenged to evaluate suspected sensitization. Study B participants underwent 21 consecutive 24-h patch applications of the 4 treatments from study A, 0.2% sodium lauryl sulfate (positive control), 0.9% saline, and a marketed gel (1% diclofenac, Voltaren). Application sites were visually scored by blinded observers for skin sensitization/irritation.In study A, 77% of participants showed minimal erythema and signs of glazing and peeling with 1% diclofenac+3% menthol by the end of the induction phase, which diminished during the challenge phase. Similar patterns were seen with menthol gel. Only 1 subject exhibited possible sensitization to 1% diclofenac+3% menthol. In study B, mean cumulative irritation score with 1% diclofenac+3% menthol was significantly higher (P<0.0001) vs. reference treatments; however, the positive control failed to produce the expected level of irritation. No treatment-related adverse events were reported.The sensitization and irritation potential of 1% diclofenac+3% menthol was greater than with the reference treatments. Comparison with positive control was not possible because it did not produce irritation under semiocclusive patch conditions. © Georg Thieme Verlag KG Stuttgart · New York.

  8. 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

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

    PubMed

    Ko, Horng-Huey; Tsai, Yi-Ting; Yen, Ming-Hong; Lin, Chun-Ching; Liang, Chan-Jung; Yang, Tsung-Han; Lee, Chiang-Wen; Yen, Feng-Lin

    2013-12-10

    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. 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. 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. The present study suggests that norartocarpetin could be used as a whitening agent in medicine and/or cosmetic industry and need further clinical study.

  10. 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.

  11. Facial skin blood flow responses to irritant stimuli in the oral cavity.

    PubMed

    Kashima, Hideaki; Hayashi, Naoyuki

    2013-03-01

    To investigate whether capsaicin and menthol stimuli elicit characteristic responses in facial skin blood flow (SkBF), we observed the facial SkBF response to low and high concentrations of capsaicin and menthol stimuli of 1-ml solution applied to the oral cavity for 20s in 17 healthy subjects. High concentration of capsaicin significantly increased the SkBF in all of the facial areas monitored. High concentration of menthol stimulus significantly decreased SkBF in the nose and increased that in the eyelid, and upper and lower lips. These results demonstrated that capsaicin and menthol stimuli in the oral cavity elicit characteristic responses in facial SkBF.

  12. Eruptive cherry angiomas and irritant symptoms after one acute exposure to the glycol ether solvent 2-butoxyethanol.

    PubMed

    Raymond, L W; Williford, L S; Burke, W A

    1998-12-01

    Seven clerical workers were evaluated in 1993, 8 months after exposure to vaporized 2-butoxyethanol (2-BE; also called butyl cellosolve or ethylene glycol monobutyl ether [EGMBE or EGBE]), which had been applied overnight to strip the floor of their file room. At the time of exposure, they had noted intense eye and respiratory irritation, marked dyspnea, nausea, and faintness, suggesting a concentration of 2-BE in the air of 200-300 parts per million (ppm). All seven workers later experienced recurrent eye and respiratory irritation, dry cough, and headache. Four months after the exposure, cherry angiomas began to appear on the arms, trunk, and thighs of six workers, who voiced concerns about the possibility of cancer. Our evaluation found no evidence of hematologic, liver, lung, or renal toxicity, but elevations in the erythrocyte sedimentation rate and blood pressure of each subject were found. Workplace air sampling found no detectable 2-BE, but traces (0.1-0.2 ppm) of formaldehyde were identified. Irritant symptoms abated after the group was moved to a room with better ventilation, and the mild hypertension gradually cleared, but new cherry angiomas have continued to appear 5 years after the acute exposure, as the initial ones persisted. These angiomas occur in healthy persons as they age but in this instance appear to have resulted from a single overexposure to 2-BE. We felt confident in reassuring the workers that they would suffer no serious consequences from this exposure.

  13. Dermal and ocular irritation studies of honeybee (Apis mellifera L.) venom.

    PubMed

    Han, Sang Mi; Lee, Kwang Gill; Yeo, Joo Hong; Pak, Sok Cheon

    2012-01-01

    The aim of this study was to access the irritant properties of bee venom (BV) after its application to skin and eye mucous membranes of the rabbit. The animals were also observed for clinical signs and mortality after the application of the test material. Six animals were used for the skin irritation test and nine rabbits for the eye irritation test. The acute BV application to the rabbit skin revealed no appreciable clinical signs throughout the observation period of 72 h and there was no mortality seen. In the eye irritation test, eye reactions were read and graded 24, 48, 72, 96 and 168 h after BV treatment. No changes in the cornea, iris or conjunctivae were observed at all time points of observations. Based on the present findings, it can be concluded that the irritation potential of BV is negligible.

  14. Comparison of different water/oil microemulsions containing diclofenac sodium: preparation, characterization, release rate, and skin irritation studies.

    PubMed

    Kantarci, Gülten; Ozgüney, Işik; Karasulu, H Yeşim; Arzik, Sevgi; Güneri, Tamer

    2007-11-02

    The aim of the present study was to make a comparison of the in vitro release rate of diclofenac sodium (DS) from microemulsion (M) vehicles containing soybean oil, nonionic surfactants (Brij 58 and Span 80), and different alcohols (ethanol [E], isopropyl alcohol [I], and propanol [P]) as cosurfactant. The optimum surfactant:cosurfactant (S:CoS) weight ratios and microemulsion areas were detected by the aid of phase diagrams. Three microemulsion formulations were selected, and their physicochemical properties were examined for the pH, viscosity, and conductivity. According to the release rate of DS, M prepared with P showed the significantly highest flux value (0.059 +/- 0.018 mg/cm(2)/h) among all formulations (P < .05). The conductivity results showed that DS-loaded microemulsions have higher conductivity values (18.8-20.2 microsiemens/cm) than unloaded formulations (16.9-17.9 microsiemens/cm), and loading DS into the formulation had no negative effect on system stability. Moreover, viscosity measurements were examined as a function of shear rate, and Newtonian fluid characterization was observed for each microemulsion system. All formulations had appropriate observed pH values varying from 6.70 to 6.85 for topical application. A skin irritation study was performed with microemulsions on human volunteers, and no visible reaction was observed with any of the formulations. In conclusion, M prepared with P may be a more appropriate formulation than the other 2 formulations studied as drug carrier for topical application.

  15. A new parameter identification method to obtain change in smooth musclecontraction state due to mechanical skin irritation

    NASA Astrophysics Data System (ADS)

    Bauer, Daniela

    2005-03-01

    A light scratch with a needle induces histamine and neuropetide release on the line of stroke and in the surrounding tissue. Histamine and neuropeptides are vasodilaters. They create vasodilation by changing the contraction state of the vascular smooth muscles and hence vessel compliance. Smooth muscle contraction state is very difficult to measure. We propose an identification procedure that determines change in compliance. The procedure is based on numerical and experimental results. Blood flow is measured by Laser Doppler Velocimetry. Numerical data is obtained by a continuous model of hierarchically arranged porous media of the vascular network [1]. We show that compliance increases after the stroke in the entire tissue. Then, compliance decreases in the surrounding tissue, while it keeps increasing on the line of stroke. Hence, blood is transported from the surrounding tissue to the line of stroke. Thus, higher blood volume on the line of stroke is obtained. [1] Bauer, D., Grebe, R. Ehrlacher, A., 2004. A three layer continuous model of porous media to describe the first phase of skin irritation. J. Theoret. Bio. in press

  16. In vitro and in vivo comparison of dermal irritancy of jet fuel exposure using EpiDerm (EPI-200) cultured human skin and hairless rats.

    PubMed

    Chatterjee, Abhijit; Babu, R Jayachandra; Klausner, M; Singh, Mandip

    2006-12-01

    The purpose of this study was to evaluate an in vitro EpiDerm human skin model (EPI-200) to study the irritation potential of jet fuels (JP-8 and JP-8+100). Parallel in vivo studies on hairless rats on the dermal irritancy of jet fuels were also conducted. Cytokines are an important part of an irritation and inflammatory cascade, which are expressed in upon dermal exposures of irritant chemicals even when there are no obvious visible marks of irritation on the skin. We have chosen two primary cytokines (IL-1alpha and TNF-1alpha) as markers of irritation response of jet fuels. Initially, the EPI-200 was treated with different quantities of JP-8 and JP-8+100 to determine quantities which did not cause significant cytotoxicity, as monitored using the MTT assay and paraffin embedded histological cross-sections. Volumes of 2.5-50 microl/tissue (approximately 4.0-78 microl/cm2) of JP-8 and JP-8+100 showed a dose dependent loss of tissue viability and morphological alterations of the tissue. At a quantity of 1.25 microl/tissue (approximately 2.0 microl/cm2), no significant change in tissue viability or morphology was observed for exposure time extending to 48 h. Nonetheless, this dose induced significant increase in IL-1alpha and TNF-alpha release versus non-treated controls after 24 and 48 h. In addition, IL-1alpha release for JP-8+100 was significantly higher than that observed for JP-8, but TNF-alpha release after 48 h exposure to these two jet fuels was the same. These findings parallel in vivo studies on hairless rats, which indicated higher irritation levels due to JP-8+100 versus JP-8. In vivo, transepidermal water loss (TEWL) and IL-1alpha expression levels followed the order JP-8+100 > JP-8 > control. Further, in vivo TNF-alpha levels for JP-8 and JP-8+100 were also elevated but not significantly different from one another. In aggregate, these findings indicate that EPI-200 tissue model can be utilized as an alternative to the use of animals in evaluating dermal

  17. 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.

  18. DEVELOPMENT OF EXPOSURE-RESPONSE MODELS FOR THE ACUTE RESPIRATORY EFFECTS OF INHALED IRRITANTS IN HUMANS

    EPA Science Inventory

    In order to conduct quantitative risk assessment with minimal uncertainty for short-term exposure to ozone and other respiratory irritants, one must identify exposure-response (E-R) models which accurately predict the distribution of the magnitudes of response (or the proportion ...

  19. DEVELOPMENT OF EXPOSURE-RESPONSE MODELS FOR THE ACUTE RESPIRATORY EFFECTS OF INHALED IRRITANTS IN HUMANS

    EPA Science Inventory

    In order to conduct quantitative risk assessment with minimal uncertainty for short-term exposure to ozone and other respiratory irritants, one must identify exposure-response (E-R) models which accurately predict the distribution of the magnitudes of response (or the proportion ...

  20. Quantitative measurement of acute corneal injury in rabbits with surfactants of different type and irritancy.

    PubMed

    Maurer, J K; Parker, R D; Petroll, W M; Carr, G J; Cavanagh, H D; Jester, J V

    1999-07-01

    We have hypothesized that differences in ocular irritancy are related to differences in extent of initial injury and that, regardless of the processes leading to tissue damage, extent of injury is the primary factor that determines the final outcome of ocular irritation. In previous in vivo confocal microscopic (CM) studies we identified quantifiable differences in the extent of corneal injury occurring with four surfactants (three anionic, one cationic) known to cause different levels of ocular irritation and demonstrated that extent of initial corneal injury was related to the magnitude of cell death. The purpose of this study was to assess the applicability of this hypothesis to a broad sampling of surfactants. Specifically, initial corneal changes induced by seven different surfactants (one anionic, three cationic, three nonionic) were measured by in vivo CM and cell death was measured by an ex vivo live/dead assay. The right eye of each rabbit was treated by placing 10 microl of a surfactant directly on the cornea. Eyes were examined macroscopically and scored for irritation at 3 h and 1 day. At 3 h and 1 day, in vivo CM was used to examine the corneas and quantitate epithelial cell size, epithelial thickness, corneal thickness, and depth of stromal injury. At 3 h and/or at 1 day, corneas were removed and excised regions were placed in culture media containing 2 microM calcein AM and 4 microM ethidium homodimer. Using laser scanning CM, the number of dead epithelial and/or stromal cells in a 300 x 300 x 170-microm3 (xyz) volume of the cornea was determined. In vivo CM and live/dead assay findings revealed three surfactants to affect only the epithelium, three surfactants to affect the epithelium and superficial stroma, and one surfactant to affect the epithelium and deep stroma. Extent of initial corneal injury reflected level of ocular irritation, and magnitude of cell death was related to the extent of initial corneal injury. These findings are consistent

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

    PubMed

    Sanchez, L; Mitjans, M; Infante, M R; Vinardell, M P

    2004-09-01

    The aim of this study was to identify new surfactants with low skin irritant properties for use in pharmaceutical and cosmetic formulations, employing cell culture as an alternative method to in vivo testing. In addition, we sought to establish whether potential cytotoxic properties were related to the size of the counterions bound to the surfactants. Cytotoxicity was assessed in the mouse fibroblast cell line 3T6 and the human keratinocyte cell line NCTC 2544 using the MTT assay and uptake of the vital dye neutral red 24 h after dosing (NRU). Lysine-derivative surfactants showed higher IC50s than did commercial anionic irritant compounds such as sodium dodecyl sulfate, proving to be no more harmful than amphoteric betaines. The aggressiveness of the surfactants depended on the size of their constituent counterions: surfactants associated with lighter counterions showed a proportionally higher aggressivity than those with heavier ones. Synthetic lysine-derivative anionic surfactants are less irritant than commercial surfactants such as sodium dodecyl sulfate and hexadecyltrimethylammonium bromide and are similar to betaines. These surfactants may offer promising applications in pharmaceutical and cosmetic preparations, representing a potential alternative to commercial anionic surfactants as a result of their low irritancy potential.

  2. Skin temperature reveals the intensity of acute stress

    PubMed Central

    Herborn, Katherine A.; Graves, James L.; Jerem, Paul; Evans, Neil P.; Nager, Ruedi; McCafferty, Dominic J.; McKeegan, Dorothy E.F.

    2015-01-01

    Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens (Gallus gallus domesticus). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research. PMID:26434785

  3. Assessing the systemic toxicity in rabbits after sub acute exposure to ocular irritant chemicals.

    PubMed

    Reshma, Cherian Sebastian; Sruthi, Sudhakaran; Syama, Santhakumar; Gayathri, Vishwanath; Mohanan, Parayanthala Valappil

    2015-03-01

    Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers (IL-1α, IL-1β, IL-8 and TNF-α) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

  4. Use of honey associated with Ananas comosus (Bromelin) in the treatment of acute irritative cough

    PubMed Central

    Peixoto, Décio Medeiros; Rizzo, José Angelo; Schor, Deborah; Silva, Almerinda Rêgo; de Oliveira, Dinaldo Cavalcanti; Solé, Dirceu; Sarinho, Emanuel

    2016-01-01

    Abstract Objective: To evaluate the immediate improvement rate of irritative cough in patients treated with the combination of Ananas comosus extract and honey (Bromelin®) compared with the use of honey alone (placebo group). Methods: Pragmatic, double-blind, randomized, parallel-group study with children aged between 2 and 15 years, with irritative cough for at least 24hours. The double-blind assessment of cough was through the number of observed coughing episodes and intensity score for a period of 10minutes of observation. The decrease of one point in the mean total score was considered as a therapeutic effect. Results: There was a reduction in coughing episodes in both groups, as well as in the cough score after 30minutes of drug or honey administration. The change in clinical score above two points, which could indicate marked improvement, occurred in five patients in the bromelin group and only in one in the placebo group, but without significant difference. There were no adverse events. Conclusions: The immediate improvement rate of irritative cough was similar in patients treated with combination of Ananas comosus extract and honey (Bromelin®) compared with the use of honey alone (placebo group). It is possible that honey has a therapeutic effect on mucus and cough characteristics (Clinical Trials: NCT01356693). PMID:27181342

  5. Applicability of in vitro tests for skin irritation and corrosion to regulatory classification schemes: substantiating test strategies with data from routine studies.

    PubMed

    Kolle, Susanne N; Sullivan, Kristie M; Mehling, Annette; van Ravenzwaay, Bennard; Landsiedel, Robert

    2012-12-01

    Skin corrosion or irritation refers to the production of irreversible or reversible damage to the skin following the application of a test substance, respectively. Traditionally, hazard assessments are conducted using the in vivo Draize skin test, but recently in vitro tests using reconstructed human epidermis (RhE) models have gained regulatory acceptance. In this study, skin corrosion (SCT) and irritation tests (SIT) using a RhE model were implemented to reduce the number of in vivo tests required by regulatory bodies. One hundred and thirty-four materials were tested from a wide range of substance classes included 46 agrochemical formulations. Results were assessed according to UN GHS, EU-CLP, ANVISA and US EPA classification schemes. There was high correlation between the two in vitro tests. Assessment of the SCT sensitivity was not possible due to the limited number of corrosives in the data set; SCT specificity and accuracy were 89% for all classification systems. Accuracy (63-76%) and sensitivity (53-67%) were low in the SIT. Specificity and concordance for agrochemical formulations alone in both the SCT and SIT were comparable to the values for the complete data set (SCT: 91% vs. 89% specificity, 91% vs. 89% accuracy and SIT: 64-88% vs. 70-85% specificity, 56-75% vs. 63-76% accuracy). Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Beneficial effects of a skin tolerance-tested moisturizing cream on the barrier function in experimentally-elicited irritant and allergic contact dermatitis.

    PubMed

    De Paépe, K; Hachem, J P; Vanpee, E; Goossens, A; Germaux, M A; Lachapelle, J M; Lambert, J; Matthieu, L; Roseeuw, D; Suys, E; Van Hecke, E; Rogiers, V

    2001-06-01

    In experimentally-induced irritant (ICD) and allergic (ACD) contact dermatitis, an oil-in-water (o/w) cream was applied to investigate its effects on a disturbed barrier function compared to untreated physiological barrier repair. Transepidermal water loss (TEWL) measurements were performed. Before the start of the experiments, the skin tolerance of the cream was examined, revealing the non-irritating characteristics of the ingredients and the absence of any contact allergic patch test reaction. In the ICD study, sodium lauryl sulfate (SLS) patches were applied to the forearms of young female volunteers. Consequently, it was observed that repeated cream application (14 days, 2x/day) significantly improved the TEWL of SLS-damaged skin, leading to a complete recovery on day 15. In the ACD study, disruption of skin barrier function was obtained by a nickel-mediated contact allergy patch (CAP) test. The cream was then applied 2x/day for 4 consecutive days. Assessment of TEWL clearly showed that recovery of the disrupted skin significantly improved after cream application in comparison to untreated barrier repair.

  7. 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.

  8. Primary irritation index and safety zone of cosmetics: retrospective analysis of skin patch tests in 7440 Korean women during 12 years.

    PubMed

    An, S M; Ham, H; Choi, E J; Shin, M K; An, S S; Kim, H O; Koh, J S

    2014-02-01

    Cosmetics are products used over long periods by the public, and their safety is very important. Several types of human tests are used widely for the evaluation of cosmetics including single patch tests, in-use tests, human repeated insult patch test (HRIPT). However, there is no clear and well-defined published objective and standardized criteria for primary skin irritation in regard to the large variety of cosmetic products. This study analysed human patch tests conducted from May 2001 to December 2012 with 4606 materials of prototype or finished cosmetic products on 7440 normal Korean women aged 18-60 years. The tested products were patched under occlusion for 24 or 48 h, and skin tolerance was assessed twice at 30 min and 24 h after patch removal using a 5-step scale according to the CTFA guidelines. Human patch tests for cosmetics were performed of 4606 cases, and 30-33 subjects participated in each case. The response in each case was calculated based on total subject number, skin reaction intensity and the number of respondents. The calculated response was standardized using the z-score, and a safety zone was provided in terms of human primary irritation in accordance with the human skin reaction evaluation criteria and usage or formula of cosmetics. This study established the safety criteria for irritation in the cosmetics field. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  9. Skin stretching for primary closure of acute burn wounds.

    PubMed

    Verhaegen, Pauline D H M; Bloemen, Monica C T; van der Wal, Martijn B A; Vloemans, Adrianus F P M; Tempelman, Fenike R H; Beerthuizen, Gerard I J M; van Zuijlen, Paul P M

    2014-12-01

    In burn care, a well-acknowledged problem is the suboptimal scar outcome from skin grafted burn wounds. With the aim of improving this, we focused on a new technique: excision of the burn wound followed by primary closure, thereby using a skin-stretching device to stretch the adjacent healthy skin. The short- and long-term effect of Skin Stretch was compared to split skin grafting (SSG) in a randomized controlled trial. Patients with burn wounds were randomized for SSG or primary wound closure using Skin Stretch. Follow-up was performed at 3 and 12 months postoperatively. The scar surface area was calculated and the scar quality was assessed, using subjective and objective measurement methods. No significant differences between the SSG and the Skin Stretch group were found for scar surface area. In the Skin Stretch group, a significant reduction of the surface area from 65.4cm(2) (13.6-129.1) to 13.4cm(2) (3.0-36.6) was found at 3 months (p=0.028) and at 12 months postoperatively (65.4cm(2) (13.6-129.1) to 33.0cm(2) (8.9-63.7), p=0.046, Wilcoxon signed ranks test). Skin Stretch for primary closure of acute burn wounds is a suitable technique and can be considered for specific circumscript full-thickness burn wounds. However, future research should be performed to provide additional scientific evidence. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  10. Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo: ex vivo permeation and skin irritation studies.

    PubMed

    Patel, Hetal K; Barot, Bhavesh S; Parejiya, Punit B; Shelat, Pragna K; Shukla, Arunkumar

    2013-02-01

    The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion based gel (MBC) of clobetasol propionate (CP) for the effective treatment of vitiligo. D-Optimal mixture experimental design was adopted to optimize the amount of oil (X(1)), S(mix) (mixture of surfactant and cosurfactant) (X(2)) and water (X(3)) in the microemulsion. The formulations were assessed for globule size (nm) (Y(1)) and solubility of CP in microemulsion (mg/ml) (Y(2)). The microemulsion containing 3% oil, 45% S(mix) and 50% water was selected as the optimized batch (ME). The globule size and solubility of CP in ME were 18.26 nm and 36.42 mg/ml respectively. Transmission electron microscopy showed that ME globules were spherical in shape. Carbopol 934P was used to convert microemulsion containing drug into gel form without affecting its structure. Ex-vivo permeation studies showed that cumulative amount of CP permeated (Q(n)) from ME, MBC and market formulation (MFCP) at 8h after application were 53.6±2.18, 28.43±0.67 and 37.73±0.77 μg cm(-2) respectively. MBC showed greater retention of CP in to skin layers than ME and MFCP. Skin irritation studies showed MBC to be significantly less irritating than MFCP. Photomicrographs and scanning electron micrographs of skin sections treated with MBC showed significant changes in the skin structure, which was attributed to the interaction of microemulsion components with skin resulting in permeation enhancement and retention of CP into skin layers. It was concluded that CP loaded gel could be a promising formulation for effective treatment of vitiligo.

  11. Current and emerging drugs for acute bacterial skin and skin structure infections: an update.

    PubMed

    Kollipara, Ramya; Downing, Christopher; Lee, Michael; Guidry, Jacqueline; Curtis, Stephen; Tyring, Stephen

    2014-09-01

    Antibiotic resistance, the emergence of multidrug-resistant bacteria and the exponential rise of methicillin-resistant Staphylococcus aureus (MRSA) acute bacterial skin and skin structure infections (ABSSSI) pose a great threat to the public health. In order to combat these threats, development of new antibiotics is vital and measures to decrease antibiotic resistance should be prioritized. This manuscript provides an overview of the current FDA-approved antibiotics and the antibiotics in development for MRSA ABSSSI. A great need exists currently for novel antibiotics to combat multidrug-resistant MRSA. As clinicians, it is imperative to implement proper management in order to reduce antibiotic resistance.

  12. Multi-laboratory validation of SkinEthic HCE test method for testing serious eye damage/eye irritation using liquid chemicals.

    PubMed

    Alépée, N; Leblanc, V; Adriaens, E; Grandidier, M H; Lelièvre, D; Meloni, M; Nardelli, L; Roper, C S; Santirocco, E; Toner, F; Van Rompay, A; Vinall, J; Cotovio, J

    2016-03-01

    A prospective multicentric study of the reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted to evaluate its usefulness to identify chemicals as either not classified for serious eye damage/eye irritation (No Cat.) or as classified (Cat. 1/Cat. 2) within UN GHS. The aim of this study was to demonstrate the transferability and reproducibility of the SkinEthic™ HCE EITL protocol for liquids and define its predictive capacity. Briefly, 60 chemicals were three times tested (double blinded) in 3 laboratories and 45 additional chemicals were tested three times in one laboratory. Good within laboratory reproducibility was achieved of at least 88.3% (53/60) and 92.4% (97/105) for the extended data set. Furthermore, the overall concordance between the laboratories was 93.3% (56/60). The accuracy of the SkinEthic™ HCE EITL for the extended dataset, based on bootstrap resampling, was 84.4% (95% CI: 81.9% to 87.6%) with a sensitivity of 99.0% (95% CI: 96.4% to 100%) and specificity of 68.5% (95% CI: 64.0% to 74.0%), thereby meeting all acceptance criteria for predictive capacity. This efficient transferable and reproducible assay is a promising tool to be integrated within a battery of assays to perform an eye irritation risk assessment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Acute skin barrier disruption with repeated tape stripping: an in vivo model for damage skin barrier.

    PubMed

    Gao, Yanrui; Wang, Xuemin; Chen, Shuangyu; Li, Shuyuan; Liu, Xiaoping

    2013-05-01

    To establish a model of standardized acute barrier disruption, investigate the response of normal human to repeated tape stripping, and analyze the change of damaged skin with non-invasive examination techniques for skin, such as TEWL and squamometry. Repeated tape stripping with corneofix was applied on three different anatomical sites; the measurement of TEWL was performed on the baseline and after every 5 strips. Then, the samples of corneofix were analyzed using Visioscan VC98 and squamometry. The parameter of TEWL and cohesion score show stable change trend. TEWL increased with frequency of stripping and were significantly higher compared with that of baseline on three sites. The results of staining of corneofix showed that the intercorneocyte cohesion is increased with the number of strips, and the more the number of strips, the more the fixation of dye per cell. The changes in the skin barrier function of different sites were different after it accepted physical stimulation, the process of damaging skin barrier could be divided into three stages based on the △TEWL. In addition, through stripping the skin of an adult, the in vivo model of damaged skin barrier could be setup. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  14. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

    PubMed

    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed.

  15. Hypothalamic--pituitary-- adrenal axis dysregulation in women with irritable bowel syndrome in response to acute physical stress.

    PubMed

    FitzGerald, Leah Z; Kehoe, Priscilla; Sinha, Karabi

    2009-11-01

    Irritable bowel syndrome (IBS) supports the concept of a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. This study investigates the neuroendocrine and psychological responses to the acute physical stress of a lumbar puncture (LP) in women with diarrhea-predominant IBS by assessing central and peripheral HPA activity and affective measures. Blood samples have been collected at baseline and immediately post- and 1 hr following LP from 13 women with IBS and 13 controls. Plasma adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine levels are analyzed. A single measure of cerebrospinal fluid (CSF) concentrations of corticotropin-releasing factor (CRF(CSF)) and norepinephrine(CSF) is noted. Affective assessments are used to rate anxiety and depression with the Hospital Anxiety and Depression Scale (HADS) and acute mood state is rated using the Stress Symptom Rating questionnaire (stress, anxiety, anger, arousal). The women with IBS display blunted ACTH and cortisol responses to the LP along with a profile of affective responsiveness suggestive of chronic psychosocial stress, although no CRF(CSF) differences between groups are observed.

  16. [Cytarabine and skin reactions in acute myeloid leukemia].

    PubMed

    Grille, Sofía; Guadagna, Regina; Boada, Matilde; Irigoin, Victoria; Stevenazzi, Mariana; Guillermo, Cecilia; Díaz, Lilián

    2013-01-01

    Cytarabine is an antimetabolite used in the treatment of acute myeloid leukemia (AML). It has many adverse effects as: myelosuppression, toxic reactions involving central nervous system, liver, gastrointestinal tract, eyes or skin. Dermatologic toxicity is often described as rare; nevertheless there are differences in the reported frequency. We performed a retrospective study including all AML treated with chemotherapy that involved cytarabine between 1st July of 2006 and 1st July of 2012; 46 patients were included with a median age of 55 years. The overall incidence of skin reactions was 39% (n = 18). Sex, age, history of atopy, history of drug reactions, or dose of cytarabine used, were not associated with them. Skin reactions were observed from 2 to 8 days after treatment started. Considering injury degree: 27.8% had grade 1, 38.9% grade 2 and 33.3% grade 3. We did not find any injury grade 4 or death associated with skin toxicity. As for the type of injury: 55.6% presented macules, 22.2% papules and 22.2% erythema. Lesions distribution was diffuse in 52% of patients, acral in 39.3%, and at flexural level in 8.7%. Adverse cutaneous reactions secondary to the administration of cytarabine are frequent in our service and include some cases with severe involvement. Although these reactions usually resolve spontaneously, they determine an increased risk of infection and a compromise of the patient quality of life.

  17. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

    PubMed

    Russo, A; Concia, E; Cristini, F; De Rosa, F G; Esposito, S; Menichetti, F; Petrosillo, N; Tumbarello, M; Venditti, M; Viale, P; Viscoli, C; Bassetti, M

    2016-04-01

    In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

  18. 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, ...

  19. 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.

  20. Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections.

    PubMed

    Ferrández, Olivia; Urbina, Olatz; Grau, Santiago

    2017-01-01

    Tedizolid phosphate has high activity against the Gram-positive microorganisms mainly involved in acute bacterial skin and skin structure infections, such as strains of Staphylococcus aureus (including methicillin-resistant S. aureus strains and methicillin-sensitive S. aureus strains), Streptococcus pyogenes, Streptococcus agalactiae, the Streptococcus anginosus group, and Enterococcus faecalis, including those with some mechanism of resistance limiting the use of linezolid. The area under the curve for time 0-24 hours/minimum inhibitory concentration (MIC) pharmacodynamic ratio has shown the best correlation with the efficacy of tedizolid, versus the time above MIC ratio and the maximum drug concentration/minimum inhibitory concentration ratio. Administration of this antibiotic for 6 days has shown its noninferiority versus administration of linezolid for 10 days in patients with skin and skin structure infections enrolled in two Phase III studies (ESTABLISH-1 and ESTABLISH-2). Tedizolid's more favorable safety profile and dosage regimen, which allow once-daily administration, versus linezolid, position it as a good therapeutic alternative. However, whether or not the greater economic cost associated with this antibiotic is offset by its shorter treatment duration and possibility of oral administration in routine clinical practice has yet to be clarified.

  1. Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

    PubMed Central

    Ferrández, Olivia; Urbina, Olatz; Grau, Santiago

    2017-01-01

    Tedizolid phosphate has high activity against the Gram-positive microorganisms mainly involved in acute bacterial skin and skin structure infections, such as strains of Staphylococcus aureus (including methicillin-resistant S. aureus strains and methicillin-sensitive S. aureus strains), Streptococcus pyogenes, Streptococcus agalactiae, the Streptococcus anginosus group, and Enterococcus faecalis, including those with some mechanism of resistance limiting the use of linezolid. The area under the curve for time 0–24 hours/minimum inhibitory concentration (MIC) pharmacodynamic ratio has shown the best correlation with the efficacy of tedizolid, versus the time above MIC ratio and the maximum drug concentration/minimum inhibitory concentration ratio. Administration of this antibiotic for 6 days has shown its noninferiority versus administration of linezolid for 10 days in patients with skin and skin structure infections enrolled in two Phase III studies (ESTABLISH-1 and ESTABLISH-2). Tedizolid’s more favorable safety profile and dosage regimen, which allow once-daily administration, versus linezolid, position it as a good therapeutic alternative. However, whether or not the greater economic cost associated with this antibiotic is offset by its shorter treatment duration and possibility of oral administration in routine clinical practice has yet to be clarified. PMID:28053508

  2. 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.

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

    DTIC Science & Technology

    2000-06-01

    role in the inflammatory response by causing dilation of the vasculature (Vallance and Collier, 1994). NO is produced from the amino acid L-arginine by...in such a short period. JP-8 would have to diffuse through the stratum corneum and into the epidermis to initiate the transcription and translation...there is a shield or umbrella of IL-I alpha in the stratum corneum and epidermis which can start a complicated sequence of inflammatory actions in the

  4. Determination of pulmonary irritant threshold concentrations of hexamethylene-1,6-diisocyanate (HDI) prepolymers by bronchoalveolar lavage in acute rat inhalation studies according to TRGS 430.

    PubMed

    Ma-Hock, L; Gamer, A O; Deckardt, K; Leibold, E; van Ravenzwaay, B

    2007-02-01

    Pulmonary irritant threshold concentrations of two hexamethylene-1,6-diisocyanate (HDI)-based prepolymers (I: polymeric emulsfier modified and II: oligomeric allophanate modified) were determined in acute inhalation studies according to TRGS 430 (Dangerous Substances Technical Rule, isocyanates, Germany), based on benchmark extrapolation of bronchoalveolar lavage fluid (BALF) total protein. It was also investigated if the method is robust enough to be transferred to an independent laboratory. Five male Wistar rats per group were exposed nose-only to the test substances as liquid aerosols to concentrations of 0, 0.5, 3, 15 mg/m(3) for both test substances with an additional test group at 50 mg/m(3) for test substance I. The duration of the exposure was 6h, followed by serial sacrifices 1 day, 3 days and 7 days post exposure. BALF was analyzed for biochemical and cytological markers indicative for injury of the bronchoalveolar region. The exposure of rats to test substance I and II caused dose depended lung irritation with BALF total protein concentration being the most sensitive indicator of pulmonary effects. The extrapolated no observed adverse effect level of test substance I was 1.1 mg/m(3) and that of test substance II 2.3 mg/m(3). The acute pulmonary irritant threshold concentrations were found to be similar to those reported by [Pauluhn, J., 2004. Pulmonary irritant potency of polyisocyanate aerosols in rats: comparative assessment of irritant threshold concentrations by bronchoalveolar lavage. J. Appl. Toxicol. 24, 231-247] for HDI-homopolymers and other HDI-based polyisocyanates, and were at least 30 times higher than the MAK (occupational exposure limit) value for the HDI monomer (0.035 mg/m(3)). Thus the EBW (exposure assessment value) for these two HDI-based prepolymers can be established at 10x MAK, i.e. at 0.35 mg/m(3).

  5. The Effect of Water Hardness on Surfactant Deposition Following Washing and Subsequent Skin Irritation in Atopic Dermatitis Patients and Healthy Controls.

    PubMed

    Danby, Simon G; Brown, Kirsty; Wigley, Andrew M; Chittock, John; Pyae, Phyoe K; Flohr, Carsten; Cork, Michael J

    2017-09-12

    Living in a hard water area is associated with an increased risk of atopic dermatitis (AD). Greater skin barrier impairment following exposure to surfactants in wash products combined with high calcium, and/or chlorine, levels in hard water is a compelling mechanism for this increase. The purpose of this study was to investigate this mechanism in individuals with and without a predisposition to skin barrier impairment. We recruited 80 subjects; healthy controls and AD patients with and without FLG mutations. The skin of each participant was washed with sodium lauryl sulfate (SLS) in water of varying hardness and chlorine concentration, rinsed and covered with chambers to determine the effects of surfactant residues. Sites washed with hard water exhibited significantly increased SLS deposits. These deposits increased transepidermal water loss and caused irritation, particularly in AD patients carrying FLG mutations. A clear effect of chlorine was not observed. Water softening by ion-exchange mitigated the negative effects of hard water. Barrier impairment resulting from the interaction between hard water and surfactants is a contributory factor to the development of AD. Installation of a water softener in early life may be able to prevent AD development. An intervention study is required to test this hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. 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 Central

    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

  8. Acute effects of cigarette smoke exposure on experimental skin flaps

    SciTech Connect

    Nolan, J.; Jenkins, R.A.; Kurihara, K.; Schultz, R.C.

    1985-04-01

    Random vascular patterned caudally based McFarlane-type skin flaps were elevated in groups of Fischer 344 rats. Groups of rats were then acutely exposed on an intermittent basis to smoke generated from well-characterized research filter cigarettes. Previously developed smoke inhalation exposure protocols were employed using a Maddox-ORNL inhalation exposure system. Rats that continued smoke exposure following surgery showed a significantly greater mean percent area of flap necrosis compared with sham-exposed groups or control groups not exposed. The possible pathogenesis of this observation as well as considerations and correlations with chronic human smokers are discussed. Increased risks of flap necrosis by smoking in the perioperative period are suggested by this study.

  9. New agents approved for treatment of acute staphylococcal skin infections

    PubMed Central

    Tatarkiewicz, Jan; Staniszewska, Anna

    2016-01-01

    Vancomycin has been a predominant treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections for decades. However, growing reservations about its efficacy led to an urgent need for new antibiotics effective against MRSA and other drug-resistant Staphylococcus aureus strains. This review covers three new anti-MRSA antibiotics that have been recently approved by the FDA: dalbavancin, oritavancin, and tedizolid. The mechanism of action, indications, antibacterial activity profile, microbial resistance, pharmacokinetics, clinical efficacy, adverse effects, interactions as well as available formulations and administration of each of these new antibiotics are described. Dalbavancin is a once-a-week, two-dose, long-acting intravenous bactericidal lipoglycopeptide antibiotic. Oritavancin, a lipoglycopeptide with bactericidal activity, was developed as a single-dose intravenous treatment for acute bacterial skin and skin-structure infections (ABSSSI), which offers simplifying treatment of infections. Tedizolid is an oxazolidinone-class bacteriostatic once-daily agent, available for intravenous as well as oral use. Increased ability to overcome bacterial resistance is the main therapeutic advantage of the novel agents over existing antibiotics. PMID:27904526

  10. Staphylococcus aureus Colonization in Acute and Chronic Skin Lesions of Patients with Atopic Dermatitis

    PubMed Central

    Park, Hae-Young; Kim, Cho-Rok; Huh, Ik-Soo; Jung, Mi-Young; Seo, Eun-Young; Park, Ji-Hye; Lee, Dong-Youn

    2013-01-01

    Background Staphylococcus aureus (SA) has peculiar abilities to colonize the skin in atopic dermatitis (AD) patients. Objective We sought to determine the colonization rates of SA in acute and chronic skin lesions of AD patients, to find any difference in colonization rates according to age and to find the influences of total immunoglobulin E (IgE) and eosinophil counts to the colonization of SA. Methods We evaluated the total IgE level and eosinophil counts, and cultured SA from the skin lesions of 687 AD patients (131 acute and 556 chronic skin lesions) and 247 control urticaria patients (July 2009 to November 2010; Samsung Medical Center Dermatology Clinic, Seoul, Korea). Results The SA colonization rates were 74%, 38% and 3% in acute, chronic skin lesions and control skin, respectively, and they were increased with age in AD patients. The colonization rate in chronic skin lesions was higher in the high IgE/eosinophilia groups as compared to the normal IgE/eosinophil groups. Conclusion The SA colonization rate was higher in AD patients and especially in acute lesions, and had a tendency to increase with age. As the colonization rates were only higher in the high IgE/eosinophilia groups of chronic skin lesions, we suggested that SA may invade the skin through barrier defects in acute skin lesions, but the colonization in chronic lesions may be orchestrated through many different factors. PMID:24371386

  11. Invasive Aspergillosis with Disseminated Skin Involvement in a Patient with Acute Myeloid Leukemia: A Rare Case

    PubMed Central

    Mert, Duygu; Iskender, Gülşen; Duygu, Fazilet; Merdin, Alparslan; Dal Mehmet, Sinan; Dogan, Mehmet; Tekgündüz, Emre; Ertek, Mustafa; Altuntaş, Fevzi

    2017-01-01

    Invasive pulmonary aspergillosis is most commonly seen in immunocompromised patients. Besides, skin lesions may also develop due to invasive aspergillosis in those patients. A 49-year-old male patient was diagnosed with acute myeloid leukemia. The patient developed bullous and zosteriform lesions on the skin after the 21st day of hospitalization. The skin biopsy showed hyphae. Disseminated skin aspergillosis was diagnosed to the patient. Voricanazole treatment was initiated. The patient was discharged once the lesions started to disappear. PMID:28626542

  12. Dalbavancin for the treatment of acute bacterial skin and skin structure infections

    PubMed Central

    Ramdeen, Sheena; Boucher, Helen W

    2015-01-01

    Introduction Acute bacterial skin and skin structure infections (ABSSSI) have increased in incidence and severity. The involvement of resistant organisms, particularly methicillin-resistant Staphylococcus aureus, presents additional challenges. The lipoglycopeptide dalbavancin has a prolonged half-life, high protein binding, and excellent tissue levels which led to its development as a once-weekly treatment for ABSSSI. In the pivotal DISCOVER 1 and DISCOVER 2 trials, dalbavancin proved non-inferior to vancomycin followed by linezolid when used sequentially for ABSSSI, forming the basis for its recent approval in the US and Europe for ABSSSI. Areas covered A literature search of published pharmacologic and clinical data was conducted to review the chemistry, pharmacodynamics, and pharmacokinetics of dalbavancin. We also discuss its development process, highlighting efficacy and safety data from pertinent clinical trials and the role it could play in the current clinical landscape. Expert opinion DISCOVER 1 and DISCOVER 2 demonstrated dalbavancin’s non-inferiority to vancomycin followed by linezolid for ABSSSI and confirmed its safety and tolerability. They were among the first trials to use new, early primary efficacy endpoints, and dalbavancin was among the first agents designated a Qualified Infectious Disease Product for expedited review. Dalbavancin may prove to be a valuable option for ABSSSI patients in whom conventional therapy is limited. PMID:26239321

  13. Clinical efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections (ABSSSI)

    PubMed Central

    Leuthner, Kimberly D; Buechler, Kristin A; Kogan, David; Saguros, Agafe; Lee, H Stephen

    2016-01-01

    Acute bacterial skin and skin structure infections (ABSSSI) are a common disease causing patients to seek treatment through the health care system. With the continued increase of drug-resistant bacterial pathogens, these infections are becoming more difficult to successfully cure. Lipoglycopeptides have unique properties that allow the drug to remain active toward both common and challenging pathogens at the infected site for lengthy periods of time. Dalbavancin, a new lipoglycopeptide, provides two unique dosing regimens for the treatment of ABSSSI. The original regimen of 1,000 mg intravenous infusion followed by a 500 mg intravenous infusion after a week has been shown as safe and effective in multiple, randomized noninferiority trials. These studies also demonstrated that dalbavancin was similar to standard regimens in terms of both safety and tolerability. Recently a single 1,500 mg dose was demonstrated to be equivalent to the dalbavancin two-dose regimen for treating ABSSSI. With the introduction of dalbavancin, clinicians have the option to provide an intravenous antimicrobial agent shown to be as effective as traditional therapies, without requiring admission into the hospitals or prescribing a medication which may not be utilized optimally. Further understanding of dalbavancin and its unusual properties can provide unique treatment situations with potential benefits for both the patient and the overall health care system, which should be further explored. PMID:27354809

  14. Inhibition of TRPV1 prevented skin irritancy induced by phenoxyethanol. A preliminary in vitro and in vivo study.

    PubMed

    Li, D-G; Du, H-Y; Gerhard, S; Imke, M; Liu, W

    2017-02-01

    Phenoxyethanol is a widely used preservative in personal care products. Transient receptor potential vanilloid 1 (TRPV1) on cell membrane is activated by TRPV1 agonist capsaicin resulting in an opening of the channel for calcium influx, which is linked with neurosensory sensations characterized by itching, burning and stinging of skin. Whether uncomfortable skin sensations caused by phenoxyethanol claimed by people having sensitive skin are also due to activation of TRPV1 has not been reported in the literature. The aim of this study was to evaluate whether the TRPV1 is involved in the induction of itching and burning sensation by phenoxyethanol. The effect of phenoxyethanol on TRPV1 was assessed in vitro on HaCaT cells. The activation of TRPV1 and its inhibition by a TRPV1 antagonist were evaluated by cellular calcium influx. TRPV1 protein expression was also investigated by Western blot. In vivo in a split-face study, phenoxyethanol formulated at 1% was compared to a formulation additionally containing a TRPV1 antagonist. By applying the formulations to the nasolabial fold, the scores of phenoxyethanol-induced sensations were compared to those of the TRPV1 antagonist. In vitro phenoxyethanol induced calcium influx in HaCaT cells in a dose-dependent manner after 20 min. This effect was abolished by a solution containing the TRPV1 antagonist trans-tert-butyl cyclohexanol (ID1609). Phenoxyethanol had no effect on the expression of TRPV1, whereas capsaicin caused a significant downregulation of this receptor in the same experiment. In vivo 1% phenoxyethanol induced a skin burning and itching sensation in a cohort of 60 of 243 Chinese female subjects being sensitive to phenoxyethanol discomfort. The uncomfortable skin sensations were significantly inhibited by ID1609. Different to capsaicin, phenoxyethanol did not downregulate the expression of TRPV1 in HaCaT cells, suggesting that different regulatory mechanisms may exist for capsaicin and phenoxyethanol. Our

  15. Differentiation between Acute Skin Rejection in Allotransplantation and T-Cell Mediated Skin Inflammation Based on Gene Expression Analysis

    PubMed Central

    Wolfram, Dolores; Morandi, Evi M.; Eberhart, Nadine; Hautz, Theresa; Hackl, Hubert; Zelger, Bettina; Riede, Gregor; Wachter, Tanja; Dubrac, Sandrine; Ploner, Christian; Pierer, Gerhard; Schneeberger, Stefan

    2015-01-01

    Advances in microsurgical techniques and immunosuppressive medication have rendered transplantation of vascularized composite allografts possible, when autologous tissue is neither available nor sufficient for reconstruction. However, skin rejection and side effects of long-term immunosuppression still remain a major hurdle for wide adoption of this excellent reconstructive technique. Histopathologic changes during acute skin rejection in vascular composite allotransplantation often mimic inflammatory skin disorders and are hard to distinguish. Hence, the identification of diagnostic and therapeutic markers specific for skin rejection is of particular clinical need. Here we present novel markers allowing for early differentiation between rejection in hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7, Il18, and Il1b expression is most indicative of distinguishing skin rejection from skin inflammatory disorders. Gene expression levels varied significantly across skin types and regions, indicating localization specific mechanism of leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene expression levels differed significantly between rejection and inflammation, independent of the skin type. In synopsis of the RNA expression profile and previously assessed protein expression, the Il1 family appears as a promising option for accurate skin rejection diagnosis and, as a following step, for development of novel rejection treatments. PMID:25756043

  16. Acute skin lesions due to localized ``hot particle`` radiation exposures

    SciTech Connect

    Baum, J.W.; Carsten, A.L.; Kaurin, D.G.L.; Schaefer, C.W.

    1996-06-01

    Purpose of the studies was to determine incidence and severity of lesions resulting from localized deposition of dose to the skin from small (<0.5 mm) discrete radioactive particles. Hanford mini-swine were exposed to localized doses from 0.2 to over 600 Gy (averaged over 1 cm{sup 2} at 70{mu}m depth) from isotopes having max beta particle energies from about 0.3-3 MeV. Incidence of erythema and scabs (indicating ulceration) were scored routinely for up to 71 days post-irradiation. Responses followed normal probability distributions, and thus, no true threshold could be defined. Ten and 50% incidence rates were deduced using probit analyses. Lowest dose producing 10% incidence was about 1 Gy for exposures to Yb-175 (0.5 MeV max energy) beta particles. Severity of lesions was estimated using diameters and persistence. From preliminary considerations of probability of induction, size, and persistence of acute lesions, a special limit for hot particle exposures in the range of 5-50 Gy may be reasonable, with an action level between about 1 Gy and the limit.

  17. [Irritant contact dermatitis. Part I. Epidemiology, etiopathogenesis and clinical manifestation].

    PubMed

    Chomiczewska, Dorota; Kieć-Swierczyńska, Marta; Krecisz, Beata

    2008-01-01

    Irritant contact dermatitis is a frequent problem in dermatology. It compromises the majority of all occupational skin diseases in most countries. It develops as a result of the environmental or work-related exposure to irritants. Cutaneous reaction depends on the intrinsic properties of the irritant, individual skin susceptibility and environmental conditions. A great morphological variety of irritant contact dermatitis and difficulties in diagnosis may lead to misdiagnosis and inadequate treatment. The prognosis is variable. Preventive measures, including education, individual skin protection and proper skin care may contribute to the reduced incidence of occupational irritant contact dermatitis.

  18. Biomimetic proopiomelanocortin suppresses capsaicin-induced sensory irritation in humans

    PubMed Central

    Fatemi, Sayed Ali; Jafarian-Dehkordi, Abbas; Hajhashemi, Valiollah; Asilian-Mahabadi, Ali

    2016-01-01

    Sensitive skin is a frequently mentioned cosmetic complaint. Addition of a biomimetic of neuromediator has recently appeared as a promising new way to cure skin care product problems. This study was aimed to assess the inhibitory effect of a biomimetic lipopeptide derived from proopiomelanocortin (bPOMC) on capsaicin-induced sensory irritation in human volunteers and also to compare its protective effect with that of the well-known anti irritant strontium chloride. The effect of each test compound was studied on 28 selected healthy volunteers with sensitive skin in accordance with a double-blind vehicle-controlled protocol. From day 1 to day 13 each group was applied the test compound (bPOMC or strontium chloride) to one wing of the nose and the corresponding placebo (vehicle) to the other side twice daily. On days 0 and 14, acute skin irritation was induced by capsaicin solution and quantified using clinical stinging test assessments. Following the application of capsaicin solution, sensory irritation was evaluated using a 4-point numeric scale. The sensations perceived before and after treatment (on days 0 and 14) was calculated for the two zones (test materials and vehicle). Ultimately the percentage of variation between each sample and the placebo and also the inhibitory effect of bPOMC compared to that of strontium chloride were reported. Clinical results showed that after two weeks treatment, the levels of skin comfort reported in the group treated with bPOMC were significantly higher than those obtained in the placebo group and the inhibitory effect of bPOMC was about 47% higher than that of strontium chloride. The results of the present study support the hypothesis that biomimetic peptides may be effective on sensitive skin. PMID:28003842

  19. Rapid analysis of the skin irritant p-phenylenediamine (PPD) in henna products using atmospheric solids analysis probe mass spectrometry.

    PubMed

    Chen, Weiyang; Nkosi, Thobile A N; Combrinck, Sandra; Viljoen, Alvaro M; Cartwright-Jones, Catherine

    2016-09-05

    Henna (Lawsonia inermis) is applied to stain keratin, present in hair, skin and fingernails, a red-orange or rust colour. Producers of temporary tattoos mix the aromatic amine compound, para-phenylenediamine (PPD) into natural henna to create 'black henna' that rapidly stains the skin black. However, PPD may cause severe delayed hypersensitivity reactions following skin contact. This study proposes a rapid direct-analysis method to detect and identify PPD using an atmospheric solids analysis probe (ASAP) coupled to a Q-ToF mass spectrometer (MS). Since laborious, multistep methods of analysis to determine PPD are undesirable, due to the instability of the compound in solution, a screening method involving no sample preparation steps was developed. Experiments were carried out to optimise the corona current, sample cone voltage, source temperature, and desolvation gas temperature to determine ideal ASAP-Q-ToF-MS analysing conditions. Eleven of the 109 henna samples, originating from various countries, tested positive for PPD when henna products were screened using ASAP-MS, without any form of sample preparation other than grinding. Ultra-performance liquid chromatography electrospray ionisation-mass spectrometry (UPLC-Q-ToF-MS) was subsequently used to confirm the results from ASAP and to determine the concentrations of PPD in henna products. The allergen was detected in the same eleven samples, with concentrations ranging from 0.05-4.21% (w/w). It can be concluded that the sensitivity of the ASAP-MS technique is sufficient (limit of detection=0.025% w/w) to allow screening of henna samples for the presence of PPD. This relatively new technique can be applied to commercial products without extraction, sample treatment or chromatographic separation. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Rapid creation of skin substitutes from human skin cells and biomimetic nanofibers for acute full-thickness wound repair.

    PubMed

    Mahjour, Seyed Babak; Fu, Xiaoling; Yang, Xiaochuan; Fong, Jason; Sefat, Farshid; Wang, Hongjun

    2015-12-01

    Creation of functional skin substitutes within a clinically acceptable time window is essential for timely repair and management of large wounds such as extensive burns. The aim of this study was to investigate the possibility of fabricating skin substitutes via a bottom-up nanofiber-enabled cell assembly approach and using such substitutes for full-thickness wound repair in nude mice. Following a layer-by-layer (L-b-L) manner, human primary skin cells (fibroblasts and keratinocytes) were rapidly assembled together with electrospun polycaprolactone (PCL)/collagen (3:1, w/w; 8%, w/v) nanofibers into 3D constructs, in which fibroblasts and keratinocytes were located in the bottom and upper portion respectively. Following culture, the constructs developed into a skin-like structure with expression of basal keratinocyte markers and deposition of new matrix while exhibiting good mechanical strength (as high as 4.0 MPa by 14 days). Treatment of the full-thickness wounds created on the back of nude mice with various grafts (acellular nanofiber meshes, dermal substitutes, skin substitutes and autografts) revealed that 14-day-cultured skin substitutes facilitated a rapid wound closure with complete epithelialization comparable to autografts. Taken together, skin-like substitutes can be formed by L-b-L assembling human skin cells and biomimetic nanofibers and they are effective to heal acute full-thickness wounds in nude mice. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  1. Discrepancies between the responses to skin prick test to food and respiratory antigens in two subtypes of patients with irritable bowel syndrome

    PubMed Central

    Soares, Rosa LS; Figueiredo, Hamilton N; Santos, Jose M; Oliveira, Rita F; Godoy, Raquel L; Mendonça, Felipe AP

    2008-01-01

    AIM: To compare the response to skin prick tests (SPTs) to food antigens (FAs) and inhalant allergens (IAs) in patients with two subtypes of irritable bowel syndrome (IBS) and healthy controls. METHODS: We compared the results of SPTs for IAs and FAs in 87 volunteers divided into three groups: diarrhea predominant IBS (D-IBS) GroupI(n = 19), constipation predominant IBS (C-IBS) Group II (n = 17), and normal controls Group III (n = 51). RESULTS: Of the 285 tests (171 for FAs and 114 for IAs) performed in GroupIwe obtained 45 (26.3%) positive responses for FA and 23 (20.1%) for IA. Of the 153 tests for FA in Group II, we obtained 66 (20.1%) positive responses, and of the 102 tests for IA, we obtained 20 (19.6%) positive responses. Of the 459 tests for FA performed in Group III, we obtained 39 (84%) positive responses, and of the 306 for IA, we obtained 52 (16.9%) positive responses. The numbers of positive responses were not significantly different between the three groups, but in the D-IBS group, the number of SPT FA responses differed significantly from those for the other two groups (P < 0.01). CONCLUSION: Despite the small number of cases studied, the higher reactivity to FAs in GroupIcompared to Groups II and III adds new information, and suggests the presence of a possible alteration in intestinal epithelial function. PMID:18494056

  2. Pyridostigmine bromide modulates topical irritant-induced cytokine release from human epidermal keratinocytes and isolated perfused porcine skin.

    PubMed

    Monteiro-Riviere, Nancy A; Baynes, Ronald E; Riviere, Jim E

    2003-02-01

    Gulf War personnel were given pyridostigmine bromide (PB) as a prophylactic treatment against organophosphate nerve agent exposure, and were exposed to the insecticide permethrin and the insect repellent N,N-diethyl-m-toluamide (DEET). The purpose of this study was to assess the effects of PB to modulate release of inflammatory biomarkers after topical chemical exposure to chemical mixtures containing permethrin and DEET applied in ethanol or water vehicles. Treatments were topically applied to isolated perfused porcine skin flaps (IPPSFs). Concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) were assayed in perfusate to probe for potential inflammatory effects after complex mixture application. IPPSFs (n=4/treatment) were topically dosed with mixtures of permethrin, DEET, and permethrin/DEET, in ethanol. Each treatment was repeated with perfusate spiked with 50 ng/ml of PB. Perfusate was also spiked with 30 ng/ml diisopropylfluorophosphate to simulate low level organophosphate nerve agent exposure. Timed IPPSF venous effluent samples (0.5,1,2,4, and 8 h) were assayed by ELISA for IL-8 and TNF-alpha and by EIA for PGE(2). Overall, PB infusion caused a decrease or IL-8 and PGE(2) release. Effects on TNF-alpha were vehicle dependent. To probe the potential mechanism of this PB effect, human epidermal keratinocyte HEK cell cultures were exposed to permethrin DEET permethrin/DEET, with and without PB in DMSO. IL-8 was assayed at 1, 2, 4, 8, 12 and 24 h. PB suppressed IL-8 in permethrin and ethanol treatment from 4 to 24 h confirming the IPPSF results. In conclusion, these studies suggest that systemic exposure to PB suppressed IL-8 release at multiple time points in two skin model systems. This interaction merits further study.

  3. Classification and labeling of industrial products with extreme pH by making use of in vitro methods for the assessment of skin and eye irritation and corrosion in a weight of evidence approach.

    PubMed

    Scheel, Julia; Heppenheimer, Andreas; Lehringer, Elke; Kreutz, Juergen; Poth, Albrecht; Ammann, Holger; Reisinger, Kerstin; Banduhn, Norbert

    2011-10-01

    Classification and labeling of products with extreme pH values (≤ 2 or ≥ 11.5) is addressed in chemicals legislation. Following determination of pH and alkaline/acid reserve, additional in vitro tests are needed, especially to substantiate results less than corrosive. However, only limited experience with the practical application of in vitro methods to determine appropriate classifications for pH extreme products is available so far. Expert judgment and weight of evidence are given major roles under the globally harmonized system of classification and labeling of chemicals (GHS) and should be performed on a sound data basis. We have used a tiered testing strategy to assess 20 industrial products (cleaning and metal pretreatment) regarding their corrosive and irritating properties towards human skin models in vitro in the EpiDerm skin corrosion and/or skin irritation test. Nine dilutions of individual compounds were additionally tested. Non-corrosive samples were tested in the Hen's egg test chorioallantoic membrane (HET-CAM). We demonstrate how data is combined in a weight of evidence expert judgment, and give examples of classification decisions. To our knowledge this is the first comprehensive analysis of industrial products with extreme pH values to determine irritating and corrosive properties by making use of in vitro methods in a weight of evidence approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. The prevalence of skin tears in the acute care setting in Singapore.

    PubMed

    Chang, Yee Y; Carville, Keryln; Tay, Ai C

    2016-10-01

    Skin tears appear to be a hidden and extensive problem despite an increased focus in the literature on skin tear epidemiology, prevention strategies and management modalities. Currently, there has been no report of skin tear epidemiology published in Singapore. The aim of the present study was to pilot the methodology by WoundWest at one of the tertairy hospitals in Singapore. The secondary objective was to determine the prevalence and current nursing management of skin tears within two selected acute medical wards in the hospital. A point prevalence survey was conducted within the two medical wards. Six registered nurses acted as the surveyors and underwent pre-survey education. Inter-rater reliability testing was conducted. Surveyors were paired and performed skin examinations on all available patients in the two wards. Data were collected on age, gender, skin tear anatomical locations, their Skin Tear Audit Research categories, dressings used on identified skin tears and related documentation. A total of 144 (98%) patients consented to skin inspections. Findings demonstrated a skin tear prevalence of 6·2%; all skin tears were found to be hospital-acquired and located on the extremities. Most (78%) were in the age range of 70-89 years. There was a dearth in nursing documentation of the skin tears identified and their management. The findings suggested that nurses were lacking in the knowledge of skin tears, and documentation, if available, was not consistent. There is an urgent clinical need for the implementation of a validated skin tear classification tool; standardised protocols for skin tear prevention and management; and a comprehensive skin tear educational programme for hospital care staff. Quarterly hospital-wide skin tear prevalence surveys are also needed to evaluate improvement strategies. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  5. Irritable Bowel Syndrome

    MedlinePlus

    ... Want to Know About Puberty Train Your Temper Irritable Bowel Syndrome KidsHealth > For Kids > Irritable Bowel Syndrome Print A ... to minimize or prevent these symptoms. What Is Irritable Bowel Syndrome? Irritable bowel syndrome (IBS) is a fairly common ...

  6. [Spotlight on sensory irritation and its treatment].

    PubMed

    Piérard-Franchimont, C; Piérard, G E

    2005-10-01

    Sensory irritation is directly bound to the concept of sensitive skin. A large proportion of the population, in particular young women, is affected. The reported symptoms are those of skin discomfort without any visible alteration of the skin. According to the subjects, the timing and the cutaneous sites, various perceptions occur, including pruritus, burning and stinging sensations. Sensory irritation is difficult to quantify because it remains subjective by essence. The condition is sometimes aggravated by some cosmetics, cleaning and cleansing products, wool contact and exposure to cold and dry climate. The responsible ingredients are often agents affecting functions of stratum corneum without being obvious chemical irritants.

  7. Transitions of care in the management of acute bacterial skin and skin structure infections: a paradigm shift.

    PubMed

    Verastegui, Jaime E; Hamada, Yukihiro; Nicolau, David P

    2016-08-01

    Acute bacterial skin and skin structure infections (ABSSSI) have evolved over a relatively short period of time to become one of the most challenging medical problems encountered in clinical practice. Notably the high incidence of methicillin-resistant S. aureus (MRSA) across the continuum of care has coincided with increased outpatient failures and higher rates of hospital admissions for parental antibiotic therapy. Consequently the management of ABSSSI constitutes a tremendous burden to the healthcare system in terms of cost of care and consumption of institutional and clinical resources. This perspective piece discusses current and new approaches to the management of ABSSSI in a hospital setting and the need for a multifaceted approach. Treatment strategies for the management through the utilization of observation units (OU), Outpatient Parental Antibiotic Therapy (OPAT), and newly developed antibiotics for the use against skin infections caused by Gram-positive bacteria will be discussed in the context of ABSSSI.

  8. Acute dissociation predicts rapid habituation of skin conductance responses to aversive auditory probes.

    PubMed

    Giesbrecht, Timo; Merckelbach, Harald; ter Burg, Linda; Cima, Maaike; Simeon, Daphne

    2008-04-01

    The present study examined how acute dissociation, trait-like dissociative symptoms, and physiological reactivity relate to each other. Sixty-nine undergraduate students were exposed to 14 aversive auditory probes, while their skin conductance responses were measured. A combination of self-reported anxiety and trait-like dissociation was found to predict variability in peritraumatic dissociation levels induced by the aversive probes. Furthermore, high levels of acute dissociation were associated with faster habituation of skin conductance responding, while trait-like dissociation was unrelated to habituation. Interestingly, individuals who reported childhood trauma displayed elevated skin conductance responses. Our findings contribute to the growing body of evidence indicating that subjective feelings of acute dissociation have their objective concomitants, notably fast habituation of physiologic responses.

  9. Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer

    PubMed Central

    van den Eijnde, Wilbert A.J.; Peppelman, Malou; Lamers, Edwin A.D.; van de Kerkhof, Peter C.M.; van Erp, Piet E.J.

    2014-01-01

    Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin. PMID:26535330

  10. Differentiating a Pressure Ulcer from Acute Skin Failure in the Adult Critical Care Patient.

    PubMed

    Delmore, Barbara; Cox, Jill; Rolnitzky, Linda; Chu, Andy; Stolfi, Angela

    2015-11-01

    The purpose of this learning activity is to provide information regarding the differentiation between pressure ulcers and acute skin failure (ASF) in critically ill patients. 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. Describe the purpose, methodology and impact of this research.2. Differentiate the pathophysiology of pressure ulcers and ASF.3. Identify risk factors and diagnostic criteria for ASF. To develop a statistical model to predict the development of acute skin failure in patients admitted to the intensive care unit (ICU) and to validate this model.Retrospective case-control, logistic regression modeling552 ICU patientsIntensive care unit patients with and without pressure ulcers (PrUs) were studied and compared on key variables sorted into the following categories: (1) disease status, (2) physical conditions, and (3) conditions of hospitalization.The variables, peripheral arterial disease (odds ratio [OR], 3.8; P = .002), mechanical ventilation greater than 72 hours (OR, 3.0; P < .001), respiratory failure (OR, 3.2; P < .001), liver failure (OR, 2.9; P = .04), and severe sepsis/septic shock (OR, 1.9; P = .02), were found to be statistically significant and independent predictors of acute skin failure in ICU patients. These variables created a predictor model for acute skin failure in the ICU.Lack of objective criteria to define acute skin failure presents a clinical conundrum for practitioners-the acknowledgment that skin failure exists, but no clear-cut diagnostic criteria in which to support its existence as a result of a paucity of empirical evidence. In certain populations, such as the critically ill patient, the phenomenon of acute skin failure may be occurring, and with the current level of evidence, these ulcers may be incorrectly identified as PrUs. Accurately distinguishing risk

  11. Evaluating the consistency of location of the most severe acute skin reaction and highest skin dose measured by thermoluminescent dosimeter during radiotherapy for breast cancer.

    PubMed

    Sun, Li-Min; Huang, Chih-Jen; Chen, Hsiao-Yun; Chang, Gia-Hsin; Tsao, Min-Jen

    2016-01-01

    We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the contrary, TLD measurement of skin dose is less likely consistent with clinical observation when the most severe skin reaction occurred at the inframammary fold, breast, and areola/nipple areas (all the p > 0.05). Considering the common site of severe skin reaction over the axillary area, TLD measurement may be an appropriate way to predict skin reaction during RT. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  12. 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, ...

  13. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    PubMed Central

    Mitra, Subhashis; Saeed, Usman; Havlichek, Daniel H; Stein, Gary E

    2015-01-01

    Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. PMID:26185459

  14. Bran: may irritate irritable bowel.

    PubMed

    Lewis, M J; Whorwell, P J

    1998-05-01

    The irritable gut is known to be hypersensitive, and it is reasonable to suspect that patients with the disorder might be hyperreactive to agents that stimulate or irritate it. This appears to be a possible explanation for the adverse effects of bran on hospital patients with this disorder, but we do not yet know how this product affects community IBS sufferers. We cannot ignore the fact that fiber and bran have major beneficial effects in other areas, not least in the reduction of colonic carcinoma. In conclusion, it is probably best to recommend that patients with IBS be left to judge for themselves whether bran helps or exacerbates their symptoms, but there is enough evidence to suggest that the current dogma of routinely treating all IBS sufferers with bran should be challenged. Proprietary sources of fiber, such as ispaghula, may be more appropriate for those IBS subjects (for example, constipated) for whom fiber supplementation is believed justified.

  15. Relative irritancy of free fatty acids of different chain length.

    PubMed

    Stillman, M A; Maibach, H I; Shalita, A R

    1975-01-01

    Free fatty acids of human skin surface lipids have previously been implicated in the pathogenesis of acne vulgaris because of their apparent irritant and comedogenic properties. Prior studies on the relative irritancy of free fatty acids revealed the saturated C8 to C14 fatty acids and a C18 dienoic unsaturated fatty acid (linoleic) to be most irritating. Saturated free fatty acids from C3 to C18, and unsaturated C18 free fatty acids were applied daily under occlusive patch tests to human skin until detectable erythema appeared. The most irritating fatty acids were C8 through C12. Of the unsaturated fatty acids tested, only linoleic acid produced irritation.

  16. Viscosupplementation of the knee: Three cases of acute Pseudoseptic Arthritis with painful and irritating complications and a literature review

    PubMed Central

    Aydın, Murat; Arıkan, Murat; Toğral, Güray; Varış, Onur; Aydın, Güle

    2017-01-01

    Acute pseudoseptic arthritis is a very rare complication that is associated with intra-articular hyaluronic acid injections, which normally involve minimal risk. The most common adverse events that are caused by hyaluronic acid injections are inflammatory reactions or flares at the injection site. In this study, we described three cases of acute pseudoseptic arthritis that was caused by hyaluronic acid; the symptoms in these cases were reminiscent of acute septic arthritis. Moreover, we performed a literature review on pseudoseptic arthritis following hyaluronic acid injections to determine the manner in which this condition can be described, diagnosed, and treated. PMID:28293455

  17. Viscosupplementation of the knee: Three cases of acute Pseudoseptic Arthritis with painful and irritating complications and a literature review.

    PubMed

    Aydın, Murat; Arıkan, Murat; Toğral, Güray; Varış, Onur; Aydın, Güle

    2017-03-01

    Acute pseudoseptic arthritis is a very rare complication that is associated with intra-articular hyaluronic acid injections, which normally involve minimal risk. The most common adverse events that are caused by hyaluronic acid injections are inflammatory reactions or flares at the injection site. In this study, we described three cases of acute pseudoseptic arthritis that was caused by hyaluronic acid; the symptoms in these cases were reminiscent of acute septic arthritis. Moreover, we performed a literature review on pseudoseptic arthritis following hyaluronic acid injections to determine the manner in which this condition can be described, diagnosed, and treated.

  18. ALLERGIC IRRITABILITY

    PubMed Central

    Lewis, Paul A.; Loomis, Dorothy

    1928-01-01

    The allergic irritability of closely inbred guinea pigs as represented by their capacity to produce hemolytic antibodies for beef and sheep corpuscles, and agglutinins for Bacillus typhosus and Bacillus abortus (Bang) differs by families and therefore is at least partly dependent on inherited characteristics. These differences show an imperfect but suggestive correlation with the differences in resistance of the same families to inoculation tuberculosis as previously determined by Wright and Lewis. The differences in antibody production also show an imperfect correlation with the differences in response in the anaphylactic reaction complex as previously determined by Lewis and Loomis. These studies suggest very strongly that the allergic irritability is one of the several inheritable characters which form a partial basis for the natural resistance to tuberculosis. The antibody-producing capacity is only satisfactorily defined when minimal or moderate amounts of antigen are used and this in single treatments. The irregularities in experimental result when repeated treatments or very large single treatments are used suggest that antibody production in the second or "acquired capacity" phase may rest on a somewhat different fundamental basis than the latent or potential natural capacity. There is some very slight evidence that production in the second phase may also be influenced by inherited qualities. PMID:19869422

  19. Association of XRCC1 variants with acute skin reaction after radiotherapy in breast cancer patients.

    PubMed

    Zhou, Liqing; Xia, Jianhong; Li, Hongliang; Dai, Jianrong; Hu, Yimin

    2010-12-01

    After irradiation results in cytotoxic effects by DNA damage, base excision repair (BER) pathway is involved in the repair of single-strand breaks and nonhomologous end joining and homologous repair of double-strand breaks caused by radiotherapy. Alterations in the function of BER DNA repair genes may affect DNA repair proficiency and influence the response of patients with cancer to radiotherapy. The association of single nucleotide polymorphisms of BER DNA repair X-ray repair cross-complementing group 1 protein (XRCC1) and risk of radiotherapy-induced ≥grade 2 acute skin reaction in patients with breast cancer was examined. It was found that the risk of ≥grade 2 acute skin toxicity after radiotherapy could be increased by 2.86-fold in patients carrying the XRCC1 -77TC and CC genotypes (p = 0.016). However, the other three coding XRCC1 variants did not influence the risk of ≥grade 2 acute skin toxicity for patients with breast cancer after radiotherapy. Our results suggested that the XRCC1 polymorphism is associated with increased risk of radiation-induced acute skin reaction in a Chinese population.

  20. The irritancy of soaps and syndets.

    PubMed

    Strube, D D; Nicoll, G

    1987-06-01

    The use of soaps and synthetic detergent (syndet) bars has been associated with skin dryness and aggravation of dermatologic conditions. A number of factors, including chemical structure, pH, and cleansing ability, have been implicated in this phenomenon. Many bars contain agents designed to ameliorate the irritancy of the bar and/or provide a skin benefit. Clinical studies have shown that soaps are generally quite irritating while syndets can range from mild to harsh. The addition of skin benefit/mildness agents such as glycerin, cocoa butter, mineral oil, or lanolin has little effect on the irritancy potential of a bar since minimal amounts of these agents are deposited on the skin. The excessive removal of skin lipids by harsh soaps and detergents can result in superficial dryness. The key to gentle cleansing is to start with a mild cleansing product and avoid overuse.

  1. Mascaras may cause irritant contact dermatitis.

    PubMed

    Lodén, M; Wessman, C

    2002-10-01

    The majority of adverse effects of cosmetics have been attributed to soaps in Dutch and English studies, but to eye makeup in a recent Swedish study. The reactions may be caused by irritants or by sensitizing substances. The aim of the present study was to evaluate the irritation potential of commercially available mascaras. The mascaras were exposed to the skin in aluminium chambers. The skin reaction was evaluated using both visual assessments of erythema and non-invasive measurements of the skin reaction. Seven mascaras were tested on 15 healthy individuals in a randomized and blinded fashion. Two of the seven tested mascaras induced pronounced skin inflammation, when applied to normal skin under occlusion. These two mascaras were based on volatile petroleum distillate, in contrast to the other five mascaras that were conventional emulsions with stearate as the main emulsifier. The findings suggest that solvent-based mascaras might induce contact dermatitis due to its content of irritating substances.

  2. Caffeine protects human skin fibroblasts from acute reactive oxygen species-induced necrosis.

    PubMed

    Silverberg, Jonathan I; Patel, Mital; Brody, Neil; Jagdeo, Jared

    2012-11-01

    Oxidative damage by reactive oxygen species (ROS) plays a major role in aging and carcinogenesis. Little is known about either the effects of acute ROS in necrosis and inflammation of skin or the therapeutic agents for prevention and treatment. Previously, our laboratory identified caffeine as an inhibitor of hydrogen peroxide (H2O2)-generated lipid peroxidation products in human skin fibroblasts. Here, we study effects of caffeine on acute ROS-mediated necrosis. Human skin fibroblasts were incubated with caffeine, followed by H2O2 challenge. Flow cytometry was used to analyze cell morphology, counts, apoptosis and necrosis, and ROS. We found that caffeine protects from H2O2 cell damage at lower (0.01 mM) and intermediate (0.1 mM) doses. The beneficial effects of caffeine appear to be mediated by a mechanism other than antioxidant function.

  3. Acute kidney injury, hyperbilirubinemia, and ischemic skin necrosis due to massive sulindac overdose.

    PubMed

    Vaughn, John L; Shah, Kejal V; Ghossein, Maroun M; Meyer, William L; Kirkpatrick, Robert B

    2015-01-01

    Sulindac is a long-acting nonsteroidal anti-inflammatory drug (NSAID) widely used for the management of osteoarthritis, rheumatoid arthritis, ankylosing sponydlitis, and acute gouty arthritis. Reports of sulindac toxicity in the literature are rare. We report the case of a 22-year old male with a history of bipolar disorder who was brought to the emergency department after ingesting approximately 15 g of sulindac in a suicide attempt. He was found to have acute kidney injury and hyperbilirubinemia. Despite aggressive fluid resuscitation, his renal function progressively worsened requiring the initiation of hemodialysis. Ten days following ingestion of sulindac, he began to develop ischemic skin changes with a gangrenous appearance in his hands and feet. He continued to receive supportive treatment, and his acute kidney injury, hyperbillirubinemia, and ischemic skin necrosis eventually resolved. Clinicians should be aware of this long-acting NSAID and its ability to cause prolonged multisystem organ dysfunction.

  4. 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

    atopic dermatits were studied and compared. In healthy volunteers increased baseline TEWL and increased light reflection from the skin, interpreted as "fair" skin, was found to be associated with increased susceptibility to SLS. Hand eczema patients were found to have fairer and thinner skin than matched controls. Increased susceptibility to SLS was found only in patients with acute eczema. Patients with atopic dermatitis had increased baseline TEWL as well as increased skin susceptibility as compared to controls. Skin susceptibility is thus influenced by individual- as well as environment-related factors. Knowledge of determinants of skin susceptibility may be useful for the identification of high-risk subjects for development of irritant contact dermatitis, and may help to prevent the formation of the disease.

  5. Revisit the 21-day cumulative irritation test - statistical considerations.

    PubMed

    Zhang, Paul; Li, Qing

    2017-03-01

    The 21-day cumulative irritation test is widely used for evaluating the irritation potential of topical skin-care products. This test consists of clinician's assessment of skin reaction of the patch sites and a classification system to categorize the test product's irritation potential. A new classification system is proposed which enables us to control the estimation error and provides a statistical confidence with regard to the repeatability of the classification.

  6. Screening for potential hazard effects from four nitramines on human eye and skin.

    PubMed

    Fjellsbø, Lise Marie; Van Rompay, An R; Hooyberghs, Jef; Nelissen, Inge; Dusinska, Maria

    2013-06-01

    Amines have potential to be used in CO2 capture and storage (CCS) technology, but as they can be released into the environment and be degraded into more toxic compounds, such as nitrosamines and nitramines, there have been concerns about their negative impact on human health. We investigated the potential toxic effects from acute exposure to dimethylnitramine (DMA-NO2), methylnitramine (MA-NO2), ethanolnitramine (MEA-NO2) and 2-methyl-2-(nitroamino)-1-propanol (AMP-NO2). The eye irritation, and skin sensitization, irritation and corrosion potential of these substances have been evaluated in vitro using the Bovine Corneal Opacity and Permeability (BCOP) assay, VITOSENS® assay, Reconstructed Human Epidermis (RHE) skin irritation test and Corrositex Skin corrosion test, respectively. Exposure to DMA-NO2 induced a mild eye irritation response, while MA-NO2, MEA-NO2 and AMP-NO2 were shown to be very severe eye irritants. MA-NO2 and MEA-NO2 were tested for skin sensitization and found to be non-sensitizers to the skin. In addition, none of the four test substances was irritant or corrosive to the skin.

  7. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature

    PubMed Central

    Salvo, N.; Barnes, E.; van Draanen, J.; Stacey, E.; Mitera, G.; Breen, D.; Giotis, A.; Czarnota, G.; Pang, J.; De Angelis, C.

    2010-01-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance—and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials. For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase ii and phase iii trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho–McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6). In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus

  8. Management of acute bacterial skin and skin structure infections with a focus on patients at high risk of treatment failure.

    PubMed

    Pulido-Cejudo, Abraham; Guzmán-Gutierrez, Mario; Jalife-Montaño, Abel; Ortiz-Covarrubias, Alejandro; Martínez-Ordaz, Jose Luis; Noyola-Villalobos, Héctor Faustino; Hurtado-López, Luis Mauricio

    2017-09-01

    Over the last 25 years, the terminology of skin and soft tissue infections, as well as their classification for optimal management of patients, has changed. The so-called and recently introduced term 'acute bacterial skin and skin structure infections' (ABSSSIs), a cluster of fairly common types of infection, including abscesses, cellulitis, and wound infections, require an immediate effective antibacterial treatment as part of a timely and cautious management. The extreme level of resistance globally to many antibiotic drugs in the prevalent causative pathogens, the presence of risk factors of treatment failure, and the high epidemic of comorbidities (e.g. diabetes and obesity) make the appropriate selection of the antibiotic for physicians highly challenging. The selection of antibiotics is primarily empirical for ABSSSI patients which subsequently can be adjusted based on culture results, although rarely available in outpatient management. There is substantial evidence suggesting that inappropriate antibiotic treatment is given to approximately 20-25% of patients, potentially prolonging their hospital stay and increasing the risk of morbidity and mortality. The current review paper discusses the concerns related to the management of ABSSSI and the patient types who are most vulnerable to poor outcomes. It also highlights the key management time-points that treating physicians and surgeons must be aware of in order to achieve clinical success and to discharge patients from the hospital as early as possible.

  9. Management of acute bacterial skin and skin structure infections with a focus on patients at high risk of treatment failure

    PubMed Central

    Pulido-Cejudo, Abraham; Guzmán-Gutierrez, Mario; Jalife-Montaño, Abel; Ortiz-Covarrubias, Alejandro; Martínez-Ordaz, Jose Luis; Noyola-Villalobos, Héctor Faustino; Hurtado-López, Luis Mauricio

    2017-01-01

    Over the last 25 years, the terminology of skin and soft tissue infections, as well as their classification for optimal management of patients, has changed. The so-called and recently introduced term ‘acute bacterial skin and skin structure infections’ (ABSSSIs), a cluster of fairly common types of infection, including abscesses, cellulitis, and wound infections, require an immediate effective antibacterial treatment as part of a timely and cautious management. The extreme level of resistance globally to many antibiotic drugs in the prevalent causative pathogens, the presence of risk factors of treatment failure, and the high epidemic of comorbidities (e.g. diabetes and obesity) make the appropriate selection of the antibiotic for physicians highly challenging. The selection of antibiotics is primarily empirical for ABSSSI patients which subsequently can be adjusted based on culture results, although rarely available in outpatient management. There is substantial evidence suggesting that inappropriate antibiotic treatment is given to approximately 20–25% of patients, potentially prolonging their hospital stay and increasing the risk of morbidity and mortality. The current review paper discusses the concerns related to the management of ABSSSI and the patient types who are most vulnerable to poor outcomes. It also highlights the key management time-points that treating physicians and surgeons must be aware of in order to achieve clinical success and to discharge patients from the hospital as early as possible. PMID:28959445

  10. Involvements of γδT Lymphocytes in Acute and Chronic Skin Wound Repair.

    PubMed

    Xu, Peng; Fu, Xiujun; Xiao, Nin; Guo, Yuanyuan; Pei, Qing; Peng, Yinbo; Zhang, Yifan; Yao, Min

    2017-08-01

    Wound healing involves three stages including inflammation, proliferation, and tissue remodeling. The underlying mechanisms remain to be further elucidated. The inflammation is characterized by spatially and temporally changing patterns of various leukocyte subsets. It is regarded as the most crucial stage since the inflammatory response is instrumental to supplying various factors and cytokines that orchestrate healing events. As a subtype of T lymphocytes, γδ T cells play an important role in skin homeostasis, tumor immunosurveillance, and wound repair. However, either the dynamics of γδ T cells in healing process or the anticipated association of γδ T cells with chronic or refractory wounds were not well understood. In this study, we determine the dynamics of γδ T cells and γδ T cell-produced effectors during acute and chronic wound repair by establishing a third-degree burn model in mice skin or human skin from diabetic patients. Our data show that the involvement of γδ T cells in acute and chronic skin wound healing. The protein levels and mRNA expressions of γδ T cell-produced effectors were increased in acute healing model, whereas those effectors were decreased in chronic repair, suggesting γδ T cells are essential for wound repair. This study probes into the significant relevance of γδ T cells with effective wound repair and provides new enlightenments for the mechanisms of the formation of chronic and/or refractory wounds.

  11. [Experimental study on preclinical quality control, urgent poison and irritation of Dendrobium aurantiacum eye drops, a class I new drug against diabetic cataract].

    PubMed

    Yi, Yan-Qun; Yang, Qiao-Hong; Su, Jun-Fang; Chen, Jian; Qi, Hui; Chen, Dan; Wei, Xiao-Yong

    2013-04-01

    To establish a quality control method of Dendrobium aurantiacum eye drops, in order to evaluate acute toxicity, irritation and irritability and lay a foundation for its development and utilization in the future. The content of gigantol and SA in D. aurantiacum eye drops were determined by high-performance liquid chromatography (HPLC). The linear ranges of gigantol and SA were 0.040 8-1.530 0 g x L(-1) (r = 0.999 9) and 0.100 8-0.504 0 g x L(-1) (r = 0.999 9), with the average recoveries being 100.8%, 99.84%, and RSD being 1.4%, 1.8% (n = 9) respectively. The sample solution was stable at room temperature within 72 h. The acute toxicity test showed no toxic reaction of D. aurantiacum eye drops in mice. The irritating test for single-dose and multiple-dose administrations of D. aurantiacum eye drops and physiological saline in rabbit eyes and skin, as well as the allergic test in guinea pigs showed no eye irritation and skin irritation and irritability. These findings indicated that D. aurantiacum eye drops are safe and stable, with a good druggability.

  12. Genetic risk score and acute skin toxicity after breast radiation therapy.

    PubMed

    Borghini, Andrea; Vecoli, Cecilia; Mercuri, Antonella; Petruzzelli, Maria Fonte; D'Errico, Maria Patrizia; Portaluri, Maurizio; Andreassi, Maria Grazia

    2014-09-01

    Genetic predisposition has been shown to affect the severity of skin complications in breast cancer patients after radiotherapy. Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of tissue radiosensitivity. We evaluated the impact of different single-nucleotide polymorphisms (SNPs) in genes related to DNA repair mechanisms and oxidative stress response combined in a GRS on acute adverse effects induced by breast radiation therapy (RT). Skin toxicity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria in 59 breast cancer patients who received RT. After genotyping, a multilocus GRS was constructed by summing the number of risk alleles. The hazard ratio (HR) for GSTM1 was 2.4 (95% confidence intervals [CI]=1.1-5.3, p=0.04). The other polymorphisms were associated to an increased adverse radiosensitivity, although they did not reach statistical significance. GRS predicted roughly 40% risk for acute skin toxicity per risk allele (HR 1.37, 95% CI=1.1-1.76, p<0.01). Patients in the top tertile had a fivefold higher risk of skin reaction (HR 5.1, 95% CI=1.2-22.8, p=0.03). Our findings demonstrate that the joint effect of SNPs from oxidative stress and DNA damage repair genes may be a promising approach to identify patients with a high risk of skin reaction after breast RT.

  13. Acute Pain Speeds Skin Barrier Recovery in Healthy Men and Women

    PubMed Central

    Graham, Jennifer E.; Song, Sunmi; Engeland, Christopher G.

    2012-01-01

    Objective Psychological stress is known to impair skin barrier recovery, but little is known about the impact of pain on skin healing processes. Our primary goals were to examine the degree to which acute pain affects recovery from skin barrier disruption, and the potential mediating impact of cortisol and catecholamines. Methods Healthy non-smokers aged 18-43 (N=53, 65% women) underwent a 3-minute cold pressor pain stimulus to their foot. Tape-stripping of forearm skin occurred at two separate locations: before (site 1) and after (site 2) the pain stimulus. Transepidural water loss (TEWL) was assessed at baseline (pre-stripping), immediately post-stripping, and at 75 minutes to determine skin barrier recovery. Cortisol and catecholamine responses were obtained from multiple saliva and plasma samples, respectively. Results Contrary to expectations, greater pain was associated with faster skin barrier recovery, even after controlling for demographics, mood, anxiety, and other factors. Those who reported higher pain showed faster recovery at site 2 compared to a) individuals who experienced lower pain; and b) their own recovery at site 1. Greater increase in norepinephrine (but not in cortisol) was also associated with faster recovery at site 2, and mediated the impact of pain on recovery. Discussion Results bolster evidence that acute pain can affect immune-related processes. It is possible that acute pain may speed recovery from dermal abrasions, although pain is likely to impair recovery from more severe wounds. As pain is an important potential target for clinical intervention, further investigation of pain, stress, and healing processes is warranted. PMID:23148814

  14. Differentially expressed miRNAs in acute wound healing of the skin: a pilot study.

    PubMed

    Li, Ping; He, Quanyong; Luo, Chengqun; Qian, Liyuan

    2015-02-01

    The aim of the present study was to compare expression of microRNAs (miRNAs) from scar and normal skin areas in patients who suffered acute injuries in the skin. A total of 9 patients with acute injuries in the skin who received surgical treatment from December 2012 to March 2013 were included in this pilot study. Specimens from the hypertrophic scar and normal skin areas were obtained from the same patient during surgery. To screen for differentially expressed miRNAs, we applied 3 statistical methods, namely the traditional t test, the false discovery rate (FDR), and a novel sure independence screening procedure based on the distance correlation (DC-SIS). We examined the functional trends and metabolic and regulatory pathways for the target genes of the identified miRNAs, and explored interaction of these miRNAs in the implication of scar healing using Ingenuity Pathway Analysis. DC-SIS identified 18 differentially expressed miRNAs, 4 of which (miR-149, miR-203a, miR-222, miR-122) were also identified by FDR. The target genes of the 4 miRNAs exhibit a variety of biological functions, and are involved in various pathways such as mitogen-activated protein kinase, Wnt signaling, and focal adhesion. We identified 1 network in which 14 out of the 18 differentially expressed miRNAs were involved. Many of the miRNAs in the network target genes were involved in cell proliferation and apoptosis.In this pilot study, we identified several miRNAs exhibiting differential expression in patients who suffered acute injuries in the skin. Further studies on these miRNAs are needed to validate our findings and explore their roles in the wound healing process of the skin.

  15. Hand disinfection: how irritant are alcohols?

    PubMed

    Löffler, Harald; Kampf, Günter

    2008-10-01

    Irritant contact dermatitis is commonly found on hands of healthcare employees and is often explained by contact to water and detergents. Studies on the dermal tolerance clearly show that the degree of skin irritation is significantly lower after application of alcohol in comparison to detergents. It has also been shown in standardised wash tests using a foam roller that the application of alcohol or water immediately after a detergent-based wash can significantly decrease the degree of skin irritation, probably due to a wash-off of residual detergent. If evidence-based hand hygiene is taught early during nurses training it can substantially reduce irritant contact dermatitis supporting initiatives of primary prevention among healthcare employees. The irritant potential of commonly used alcohols in hand antiseptics is very low. If the skin is pre-irritated, e.g. by detergents or water, alcohols can cause a burning sensation which is, however, not an allergic reaction and does not further harm the skin. True allergic reactions to alcohols have so far not been confirmed. From the dermatological point of view the use of alcohols for hand hygiene has clear advantages over washing with water and detergents.

  16. Acute propranolol infusion stimulates protein synthesis in rabbit skin wound.

    PubMed

    Zhang, Xiao-Jun; Meng, Chengyue; Chinkes, David L; Finnerty, Celeste C; Aarsland, Asle; Jeschke, Marc G; Herndon, David N

    2009-05-01

    Propranolol administration has been demonstrated to improve cardiac work, decrease energy expenditure, and attenuate lipolysis in burned patients; however, its effect on wound healing has not been reported. In rabbits, a partial-thickness skin donor site wound was created on the back, and catheters were placed in the carotid artery and jugular vein. A nasogastric feeding tube was placed for enteral feeding. On day 5 after injury, stable isotope tracers were infused to determine protein and DNA kinetics in the wound. Propranolol hydrochloride was injected in 1 group during the tracer infusion to decrease heart rate, and the other group without propranolol injection served as a control. The propranolol infusion decreased heart rate by 21%. The protein fractional synthetic rate in the wound was greater in the propranolol group (8.6 +/- 0.9 vs 6.1 +/- 0.5%/day, P < .05). Wound protein fractional breakdown rates were not significantly different. The rate of protein deposition (synthesis - breakdown) was increased in the propranolol group (5.0 +/- 1.2 vs 2.8 +/- 0.7%/day, P = .07). Wound DNA fractional synthetic rates were comparable. The protein fractional synthetic rate was correlated with percent decrease in heart rate, but expression of the beta-adrenergic receptors and downstream signaling cascades in local wounds were not affected after propranolol treatment. Propranolol infusion increased wound protein synthetic rate and tended to increase wound protein deposition rate, which might be beneficial to wound healing. These changes might reflect a systemic response to the beta-adrenergic blockade.

  17. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    SciTech Connect

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-12-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

  18. Vascular responses in glabrous and nonglabrous skin during acute mental stress in physically trained humans.

    PubMed

    Yano, Hiroki; Sone, Ryoko; Yamazaki, Fumio

    2009-12-01

    Acute mental stress induces sympathetic activation and influences vasomotor control in various organs. In the present study, to better understand the effect of physical training on peripheral vasomotor control during acute mental stress, we compared the skin vascular responses to mental arithmetic (MA) in physically trained and untrained humans. Eight physically trained (T group) and eight untrained (UT group) healthy volunteers performed 2 min of MA aloud in the supine position under a thermoneutral condition (28 degrees C). Skin blood flow (laser-Doppler flowmetry) and local temperature were monitored at the glabrous (palm, sole) and nonglabrous (forearm, calf) sites. Cutaneous vascular conductance (CVC) was evaluated from the ratio of blood flow to mean arterial pressure (tonometry). Local sweating rate (SR) was measured in the sole and calf by the ventilated capsule method. In the T group, the CVC at glabrous sites consistently decreased (P < 0.05) during MA, while in the UT group, the stress-induced decreases in CVC were transient and gradually recovered during MA. The patterns of changes in CVC at the nonglabrous sites were substantially similar to those at the glabrous sites, but the decreases in CVC at the nonglabrous sites were smaller (P < 0.05) than those at the glabrous sites in both groups. Local temperature at the glabrous sites (especially in the sole) showed higher (P < 0.05) values in the T group compared with the UT group. The SR in the sole and calf were increased (P < 0.05) during MA but did not differ between the two groups. These findings suggest that physical training acts to heighten skin temperature at the glabrous sites but not at the nonglabrous sites. It is also suggested that the change of skin temperature by physical training modifies sympathetic vasomotor control in glabrous and nonglabrous skin during acute mental stress in the peripheral level.

  19. A Qualitative Analysis of Acute Skin Toxicity among Breast Cancer Radiotherapy Patients

    PubMed Central

    Schnur, Julie B.; Ouellette, Suzanne C.; DiLorenzo, Terry A.; Green, Sheryl; Montgomery, Guy H.

    2013-01-01

    Objectives One of the most common acute side effects of breast cancer radiotherapy is treatment induced skin changes, referred to as skin toxicity. Yet no research to date has focused expressly on skin toxicity-related quality of life in breast cancer radiotherapy patients. Therefore, our aim was to use qualitative approaches to better understand the impact of skin toxicity on quality of life. Methods Semi-structured interviews were conducted with 20 women (Stage 0-III breast cancer), during their last week of external beam radiotherapy. Each interview was transcribed verbatim, and thematic analysis was performed. Results Three themes were identified based on the interview responses: First, skin changes affect multiple dimensions of quality of life. They cause physical discomfort, body image disturbance, emotional distress, and impair both day-to-day functioning and satisfaction with radiation treatment. Second, individual differences affect women’s experiences. Generally African-American women, younger women, women who are not currently in a relationship, women who are being treated during the summer, and women who are more invested in their appearance are more distressed by skin toxicity. Third, women use a variety of symptom management strategies including self-medication, complementary/alternative medicine approaches, and psychological strategies. Conclusions Implications of results are: 1) Skin toxicity affects numerous dimensions of quality of life, and assessment approaches and psychosocial interventions should address this; 2) individual differences may affect the experience of skin toxicity, and should be considered in treatment and education approaches; and 3) participants’ own creativity and problem-solving should be used to improve the treatment experience. PMID:20238306

  20. A qualitative analysis of acute skin toxicity among breast cancer radiotherapy patients.

    PubMed

    Schnur, Julie B; Ouellette, Suzanne C; Dilorenzo, Terry A; Green, Sheryl; Montgomery, Guy H

    2011-03-01

    One of the most common acute side effects of breast cancer radiotherapy is treatment-induced skin changes, referred to as skin toxicity. Yet no research to date has focused expressly on skin toxicity-related quality of life (QOL) in breast cancer radiotherapy patients. Therefore, our aim was to use qualitative approaches to better understand the impact of skin toxicity on QOL. Semistructured interviews were conducted with 20 women (Stage 0-III breast cancer), during their last week of external beam radiotherapy. Each interview was transcribed verbatim, and thematic analysis was performed. Three themes were identified based on the interview responses: First, skin changes affect multiple dimensions of QOL. They cause physical discomfort, body image disturbance, emotional distress, and impair both day-to-day functioning and satisfaction with radiation treatment. Second, individual differences affect women's experiences. Generally African American women, younger women, women who are not currently in a relationship, women who are being treated during the summer, and women who are more invested in their appearance are more distressed by skin toxicity. Third, women use a variety of symptom management strategies including self-medication, complementary/alternative medicine approaches, and psychological strategies. Implications of results are as follows: (1) skin toxicity affects numerous dimensions of QOL, and assessment approaches and psychosocial interventions should address this; (2) individual differences may affect the experience of skin toxicity and should be considered in treatment and education approaches; and (3) participants' own creativity and problem-solving should be used to improve the treatment experience. Copyright © 2010 John Wiley & Sons, Ltd.

  1. Non-thermal air plasma promotes the healing of acute skin wounds in rats

    PubMed Central

    Kubinova, S.; Zaviskova, K.; Uherkova, L.; Zablotskii, V.; Churpita, O.; Lunov, O.; Dejneka, A.

    2017-01-01

    Non-thermal plasma (NTP) has nonspecific antibacterial effects, and can be applied as an effective tool for the treatment of chronic wounds and other skin pathologies. In this study we analysed the effect of NTP on the healing of the full-thickness acute skin wound model in rats. We utilised a single jet NTP system generating atmospheric pressure air plasma, with ion volume density 5 · 1017 m−3 and gas temperature 30–35 °C. The skin wounds were exposed to three daily plasma treatments for 1 or 2 minutes and were evaluated 3, 7 and 14 days after the wounding by histological and gene expression analysis. NTP treatment significantly enhanced epithelization and wound contraction on day 7 when compared to the untreated wounds. Macrophage infiltration into the wound area was not affected by the NTP treatment. Gene expression analysis did not indicate an increased inflammatory reaction or a disruption of the wound healing process; transient enhancement of inflammatory marker upregulation was found after NTP treatment on day 7. In summary, NTP treatment had improved the healing efficacy of acute skin wounds without noticeable side effects and concomitant activation of pro-inflammatory signalling. The obtained results highlight the favourability of plasma applications for wound therapy in clinics. PMID:28338059

  2. Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin.

    PubMed

    Zhou, Bing-Rong; Ma, Li-Wen; Liu, Juan; Zhang, Jia-An; Xu, Yang; Wu, Di; Permatasari, Felicia; Luo, Dan

    2016-01-01

    Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm(2)) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage.

  3. Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin

    PubMed Central

    Ma, Li-wen; Liu, Juan; Zhang, Jia-an; Xu, Yang; Wu, Di; Permatasari, Felicia

    2016-01-01

    Aim. We explored the effects of soy oligopeptides (SOP) in ultraviolet B- (UVB-) induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED) of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI), melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm2) for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs), p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage. PMID:27478534

  4. Population pharmacokinetics of ceftaroline in patients with acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia.

    PubMed

    Van Wart, Scott A; Forrest, Alan; Khariton, Tatiana; Rubino, Christopher M; Bhavnani, Sujata M; Reynolds, Daniel K; Riccobene, Todd; Ambrose, Paul G

    2013-11-01

    Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for ceftaroline was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin and skin structure infection (ABSSSI). Data from 128 patients with community-acquired bacterial pneumonia (CABP) were used for external model validation. Healthy subjects received 50-2,000 mg ceftaroline fosamil via intravenous (IV) infusion over 1 hour or intramuscular (IM) injection q12h or q24h. ABSSSI and CABP patients received 600 mg of ceftaroline fosamil IV over 1 hour q12h. A three-compartment model with zero-order IV or parallel first-order IM input and first-order elimination described ceftaroline fosamil PK. A two-compartment model with first-order conversion of prodrug to ceftaroline and parallel linear and saturable elimination described ceftaroline PK. Creatinine clearance was the primary determinant of ceftaroline exposure. Good agreement between the observed data and both population (r(2)  = 0.93) and individual post-hoc (r(2)  = 0.98) predictions suggests the PPK model can adequately approximate ceftaroline PK using covariate information. Such a PPK model can evaluate dose adjustments for patients with renal impairment and generate ceftaroline exposures for use in pharmacokinetic-pharmacodynamic assessments of efficacy in patients with ABSSSI or CABP.

  5. Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection.

    PubMed

    Cates, Jordan E; Mitrani-Gold, Fanny S; Li, Gang; Mundy, Linda M

    2015-08-01

    A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Skin toxicity of propranolol in guinea pigs.

    PubMed

    Kobayashi, I; Hosaka, K; Maruo, H; Saeki, Y; Kamiyama, M; Konno, C; Gemba, M

    1999-05-01

    The skin toxicities of propranolol were studied in guinea pigs. In the primary and cumulative skin irritation studies, the skin reactions and the histopathological changes were observed in all animals treated with propranolol, and those tended to increase with the increase of propranolol dosage. The skin reactions increased with the application times of propranolol up to 7 days in the cumulative skin irritation study. In the skin sensitization, the phototoxicity and the skin photosensitization studies, no skin reactions were observed in any animals used in the studies. These results indicate that propranolol caused skin irritation, but was negative for skin sensitization, phototoxicity and skin photosensitization in guinea pigs.

  7. Early Clinical Response as a Predictor of Late Treatment Success in Patients With Acute Bacterial Skin and Skin Structure Infections: Retrospective Analysis of 2 Randomized Controlled Trials.

    PubMed

    Nathwani, Dilip; Corey, Ralph; Das, Anita F; Sandison, Taylor; De Anda, Carisa; Prokocimer, Philippe

    2017-01-15

    In the treatment of acute bacterial skin and skin structure infections, pooled data from 2 clinical trials (N = 1333 patients) showed that programmatic and investigator-assessed early treatment success both had a high positive predictive value (94.3%-100.0%) for late clinical cure, including among hospitalized patients. The negative predictive value of programmatic early success was <20%. These exploratory findings require prospective real-world evaluation.

  8. Multi-laboratory evaluation of SkinEthic HCE test method for testing serious eye damage/eye irritation using solid chemicals and overall performance of the test method with regard to solid and liquid chemicals testing.

    PubMed

    Alépée, N; Adriaens, E; Grandidier, M H; Meloni, M; Nardelli, L; Vinall, C J; Toner, F; Roper, C S; Van Rompay, A R; Leblanc, V; Cotovio, J

    2016-08-01

    A prospective multicentre study of the reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted to evaluate its usefulness to identify chemicals as either not classified for serious eye damage/eye irritation (No Cat.) or as classified (Cat. 1/Cat. 2) within UN GHS. The aim of this study was to demonstrate the transferability and reproducibility of the SkinEthic™ HCE EITS protocol for solids and define its predictive capacity. Briefly, 60 chemicals were three times tested (double blinded) in 3 laboratories and 35 additional chemicals were tested three times in one laboratory. Good within laboratory reproducibility was achieved of at least 95% (57/60) and 96.8% (92/95) for the extended data set. Furthermore, the overall concordance between the laboratories was 96.7% (58/60). The accuracy of the SkinEthic™ HCE EITS for the extended dataset, based on bootstrap resampling, was 81.0% (95% CI: 78.9% to 83.2%) with a sensitivity of 90.5% (95% CI: 88.1% to 92.9%) and specificity of 73.6% (95% CI: 71.7% to 75.5%). Overall, 200 chemicals were tested (105 liquids (EITL protocol) and 95 solids (EITS protocol)) resulting in a sensitivity of 95.2%, specificity of 72.1% and accuracy of 83.7%, thereby meeting all acceptance criteria for predictive capacity. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Anti-inflammatory activities of colloidal oatmeal (Avena sativa) contribute to the effectiveness of oats in treatment of itch associated with dry, irritated skin.

    PubMed

    Reynertson, Kurt A; Garay, Michelle; Nebus, Judith; Chon, Suhyoun; Kaur, Simarna; Mahmood, Khalid; Kizoulis, Menas; Southall, Michael D

    2015-01-01

    Oat (Avena sativa) in colloidal form is a centuries-old topical treatment for a variety of skin conditions, including skin rashes, erythema, burns, itch, and eczema; however, few studies have investigated the exact mechanism of action for the anti-inflammatory activity of colloidal oatmeal. Four extracts of colloidal oatmeal were made with various solvents and tested in anti-inflammatory and antioxidant assays. In addition, an investigator blind study was performed with twenty-nine healthy female subjects who exhibited bilateral mild to moderate itch with moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. Extracts of colloidal oatmeal diminished pro-inflammatory cytokines in vitro and the colloidal oat skin protectant lotion showed significant clinical improvements in skin dryness, scaling, roughness, and itch intensity. These results demonstrate that colloidal oat extracts exhibit direct anti-oxidant and anti-inflammatory activities, which may provide the mechanisms for observed dermatological benefits while using the colloidal oatmeal skin protectant lotion.

  10. Assessment of the Dermal and Ocular Irritation Potential of Lomefloxacin by Using In Vitro Methods

    PubMed Central

    Ahn, Jun-Ho; Eum, Ki-Hwan

    2010-01-01

    The evaluation of eye and skin irritation potential is essential to ensuring the safety of human in contact with a wide variety of substances. Despite this importance of irritation test, little is known with respect to the irritation potency of lomefloxacin, a fluoroquinolone antibiotic, which has been known to cause phototoxicity with an abnormal reaction of the skin. Thus, to investigate the tendency of lomefloxacin to cause eye and skin irritation, we carried out in vitro eye irritation test using Balb/c 3T3, and in vitro skin irritation test using KeraSkinTM human skin model system. 3T3 neutral red uptake assay has been proposed as a potential replacement alternative for the Draize Eye irritation test. In this study, the IC50 value obtained for lomefloxacin was 375 μg. According to the classification model used for determining in vitro categories, lomefloxacin was classified as moderately irritant. For evaluation of skin irritation, engineered epidermal equivalents (KeraSkinTM) were subjected to 10 and 25 mg of lomefloxacin for 15 minutes. Tissue damage was assessed by tissue viability evaluation, and by the release of a pro-inflammatory mediator, interleukin-1α. Lomefloxacin increased the interleukin-1α release after 15 minutes of exposure and 42 hours of post incubation, although no decrease in viability was observed. Therefore, lomefloxacin is considered to be moderately irritant to skin and eye. PMID:24278500

  11. Low-dose radiation modifies skin response to acute gamma-rays and protons.

    PubMed

    Mao, Xiao Wen; Pecaut, Michael J; Cao, Jeffrey D; Moldovan, Maria; Gridley, Daila S

    2013-01-01

    The goal of the present study was to obtain pilot data on the effects of protracted low-dose/low-dose-rate (LDR) γ-rays on the skin, both with and without acute gamma or proton irradiation (IR). Six groups of C57BL/6 mice were examined: a) 0 Gy control, b) LDR, c) Gamma, d) LDR+Gamma, e) Proton, and f) LDR+Proton. LDR radiation was delivered to a total dose of 0.01 Gy (0.03 cGy/h), whereas the Gamma and Proton groups received 2 Gy (0.9 Gy/min and 1.0 Gy/min, respectively). Assays were performed 56 days after exposure. Skin samples from all irradiated groups had activated caspase-3, indicative of apoptosis. The significant (p<0.05) increases in immunoreactivity in the Gamma and Proton groups were not present when LDR pre-exposure was included. However, the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay for DNA fragmentation and histological examination of hematoxylin and eosin-stained sections revealed no significant differences among groups, regardless of radiation regimen. The data demonstrate that caspase-3 activation initially triggered by both forms of acute radiation was greatly elevated in the skin nearly two months after whole-body exposure. In addition, LDR γ-ray priming ameliorated this response.

  12. Impact of hypofractionation and tangential beam IMRT on the acute skin reaction in adjuvant breast cancer radiotherapy.

    PubMed

    Rudat, Volker; Nour, Alaa; Ghaida, Salam Abou; Alaradi, Aziz

    2016-07-30

    The purpose of the study was to evaluate the impact of multiple prognostic factors on the acute skin reaction in adjuvant breast cancer radiotherapy, in particular the impact of hypofractionation (HF) compared to conventional fractionation (CF) and tangential beam (TB) IMRT compared to three-dimensional conformal radiotherapy (3DCRT). Two-hundred and sixty-six breast cancer patients with postoperative radiotherapy after breast conserving surgery or mastectomy were retrospectively evaluated. Patients were treated with HF (15 fractions of 2.67 Gy; n = 121) or CF (28 fractions of 1.8 Gy or 25 fractions of 2.0 Gy; n = 145) and TB-IMRT (n = 151) or 3DCRT (n = 115). The acute skin reactions were prospectively assessed using the CTCAE v4 grading scale. Ordinal regression analysis was used to assess the impact of possible prognostic factors on the maximal acute skin reaction. Grade 2 skin reactions were observed in 19 % of the patients treated with CF compared to 2 % treated with HF. On univariate analysis, the fractionation regimen, the PTV (breast versus chest wall), the volume of the PTV and the body mass index were significant prognostic factors for the maximum acute skin reaction. On multivariate analysis, the fractionation regimen (p < 0.00001) and the volume of the PTV (p = 0.0002) remained as independent significant factors. Our data suggest that HF is associated with a significantly reduced maximal acute skin reaction compared to CF.

  13. [Acute skin toxicity in breast intensity modulated radiotherapy using field in field technique].

    PubMed

    Blanchecotte, J; Ruffier-Loubière, A; Reynaud-Bougnoux, A; Barillot, I

    2015-04-01

    The optimization with presegmentation irradiation technique (Dosisoft™), used in treatment of breast carcinomas, facilitates the treatment delivery and improves radioprotection. The objective of our study was to evaluate the potential impact of this innovative technique on the acute skin toxicity especially on the rate of moist desquamation during irradiation of the whole breast after conservative surgery. The scores of acute skin toxicity observed at 50 Gy in 103 patients treated with the presegmentation technique were compared to those of 101 patients with similar breast size treated with a classic 3D technique. All patients received 50 Gy/2 Gy per fraction, 5 days a week using 4 MV photon beam. The boost on the tumoural bed was realized according to conventional technique. Using the NCI-CTCAE V4, the skin toxicity was recorded every week during the medical visit. Moreover, the following factors that could induce skin toxicity have been studied: breast size, body mass index, age, prior chemotherapy, concurrent administration of trastuzumab, hypertension, diabetes, smoking habits and statin uptake. The incidence of moist desquamation observed in all sites, has been decreased to only 9.8% in the presegmentation group versus 16.8% in the test group, the difference being not statistically significant OR=0.53 [0.23; 1.22] (P=0.13). In univariate analysis the presegmentation technique enabled a significant decrease of 4.4 Gy in mean, of the value of maximum dose (P=0.001). The other risk factors of skin toxicity are the increase of breast size (P<0.001), a high body mass index (P<0.001), hypertension (P=0.03) and concurrent administration of trastuzumab (P=0.07). In multivariate analysis, the two remaining significant factors are breast size (OR=1.004 [1.002; 1.006]) and trastuzumab administration (OR=4.95 [1.17; 20.79]). The comparison of the skin toxicity induced by the presegmentation or the reference technique shows a trend regarding the improvement of the skin

  14. Profile of tedizolid phosphate and its potential in the treatment of acute bacterial skin and skin structure infections

    PubMed Central

    Hall, Ronald G; Michaels, Heidi N

    2015-01-01

    Tedizolid phosphate is the first once-daily oxazolidinone approved by the United States Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections (ABSSSI). It is more potent in vitro than linezolid against methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive pathogens causing ABSSSI, even retaining activity against some linezolid-resistant strains. Tedizolid is approximately 90% protein bound, leading to lower free-drug concentrations than linezolid. The impact of the effect of food, renal or hepatic insufficiency, or hemodialysis on tedizolid’s pharmacokinetic have been evaluated, and no dosage adjustment is needed in these populations. In animal and clinical studies, tedizolid’s effect on bacterial killing is optimized by the free-drug area under the curve to minimum inhibitory concentration ratio (fAUC/MIC). The 200 mg once-daily dose is able to achieve the target fAUC/MIC ratio in 98% of simulated patients. Two Phase III clinical trials have demonstrated the noninferiority of tedizolid 200 mg once daily for 6 days to linezolid 600 mg twice daily for 10 days. In vitro, animal, and clinical studies have failed to demonstrate that tedizolid inhibits monoamine oxidase to a clinically relevant extent. Tedizolid has several key advantages over linezolid including once daily dosing, decreased treatment duration, minimal interaction with serotonergic agents, possibly associated with less adverse events associated with the impairment of mitochondrial protein synthesis (eg, myelosuppression, lactic acidosis, and peripheral/optic neuropathies), and retains in vitro activity against linezolid-resistant gram-positive bacteria. Economic analyses with tedizolid are needed to describe the cost-effectiveness of this agent compared with other options used for ABSSSI, particularly treatment options active against MRSA. PMID:25960671

  15. The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice.

    PubMed

    Gunaseelan, Srithar; Balupillai, Agilan; Govindasamy, Kanimozhi; Muthusamy, Ganesan; Ramasamy, Karthikeyan; Shanmugam, Mohana; Prasad, N Rajendra

    2016-07-06

    In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280-320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm(-2)) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB-induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF-κB, TNF-α, IL-6, COX-2, VEGF, TGF-β1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis.

  16. Cutaneous exposure to vesicant phosgene oxime: Acute effects on the skin and systemic toxicity.

    PubMed

    Tewari-Singh, Neera; Goswami, Dinesh G; Kant, Rama; Croutch, Claire R; Casillas, Robert P; Orlicky, David J; Agarwal, Rajesh

    2017-02-15

    Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanching of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 16 CFR 1500.41 - Method of testing primary irritant substances.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... § 1500.41 Method of testing primary irritant substances. Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of the albino rabbit, clipped free of hair. A minimum of six subjects are used in abraded and intact skin tests. Introduce under a square patch, such as...

  18. Sex differences in skin carotenoid deposition and acute UVB-induced skin damage in SKH-1 hairless mice after consumption of tangerine tomatoes

    PubMed Central

    Kopec, Rachel E.; Schick, Jonathan; Tober, Kathleen L.; Riedl, Ken M.; Francis, David M.; Young, Gregory S.; Schwartz, Steven J.; Oberyszyn, Tatiana M.

    2015-01-01

    Scope UVB exposure, a major factor in the development of skin cancer, has differential sex effects. Tomato product consumption reduces the intensity of UVB-induced erythema in humans, but the mechanisms are unknown. Methods and results Four week old SKH-1 hairless mice (40 females, 40 males) were divided into two feeding groups (control or with 10% tangerine tomatoes naturally rich in UV-absorbing phytoene and phytofluene) and two UV exposure groups (with or without UV). After 10 weeks of feeding, the UV group was exposed to a single UV dose and sacrificed 48 hours later. Blood and dorsal skin samples were taken for carotenoid analysis. Dorsal skin was harvested to assess sex and UV effects on carotenoid deposition, inflammation (skinfold thickness, myeloperoxidase levels) and DNA damage (cyclobutane pyrimidine dimers, p53). Females had significantly higher levels of both skin and blood carotenoids relative to males. UV exposure significantly reduced skin carotenoid levels in females but not males. Tomato consumption attenuated acute UV-induced increases in CPD in both sexes, and reduced myeloperoxidase activity and % p53 positive epidermal cells in males. Conclusion Tangerine tomatoes mediate acute UV-induced skin damage in SKH-1 mice via reduced DNA damage in both sexes, and through reduced inflammation in males. PMID:26394800

  19. Exploring the biomechanical load of a sliding on the skin: understanding the acute skin injury mechanism of player-surface interaction.

    PubMed

    van den Eijnde, Wilbert; Meijer, Kenneth; Lamers, Edwin; Peppelman, Malou; van Erp, Piet

    2017-09-01

    Currently, there is a shortage of biomechanical data regarding acute skin injury mechanisms that are involved in player-surface contact in soccer on artificial turf. It is hypothesized that peak loads on the skin during the landing phase are an important factor in causing an acute skin injury. Simultaneously, video analysis and load measurements using an in-ground force plate of the landing phase of a sliding tackle were recorded and correlated with observed clinical skin lesions. Video analysis revealed two sliding techniques: a horizontal jump and a sliding-in technique. The first technique resulted in both significantly higher vertical and horizontal peak forces during impact on the knee (2.3±0.4 kN and 1.4±0.5 kN) and thigh (4.9±0.9 kN and 1.8±0.5 kN). In combination with the observed skin lesion areas, a combined normal-shear stress of at least 24 and 14 N.cm-2 induce abrasion injuries on dry artificial turf. The findings of this study confirm that high peak stresses during the landing phase of a sliding is critical for inducing skin injuries on the knee and thigh. Reducing these peak shear stresses could be an important first step towards preventive measures.

  20. Sex differences in skin carotenoid deposition and acute UVB-induced skin damage in SKH-1 hairless mice after consumption of tangerine tomatoes.

    PubMed

    Kopec, Rachel E; Schick, Jonathan; Tober, Kathleen L; Riedl, Ken M; Francis, David M; Young, Gregory S; Schwartz, Steven J; Oberyszyn, Tatiana M

    2015-12-01

    UVB exposure, a major factor in the development of skin cancer, has differential sex effects. Tomato product consumption reduces the intensity of UVB-induced erythema in humans, but the mechanisms are unknown. Four-week-old SKH-1 hairless mice (40 females, 40 males) were divided into two feeding groups (control or with 10% tangerine tomatoes naturally rich in UV-absorbing phytoene and phytofluene) and two UV exposure groups (with or without UV). After 10 weeks of feeding, the UV group was exposed to a single UV dose and sacrificed 48 h later. Blood and dorsal skin samples were taken for carotenoid analysis. Dorsal skin was harvested to assess sex and UV effects on carotenoid deposition, inflammation (skinfold thickness, myeloperoxidase levels), and DNA damage (cyclobutane pyrimidine dimers, p53). Females had significantly higher levels of both skin and blood carotenoids relative to males. UV exposure significantly reduced skin carotenoid levels in females but not males. Tomato consumption attenuated acute UV-induced increases in CPD in both sexes, and reduced myeloperoxidase activity and percent p53 positive epidermal cells in males. Tangerine tomatoes mediate acute UV-induced skin damage in SKH-1 mice via reduced DNA damage in both sexes, and through reduced inflammation in males. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Malondialdehyde-Derived Epitopes In Human Skin Result From Acute Exposure To Solar UV And Occur In Nonmelanoma Skin Cancer Tissue

    PubMed Central

    Williams, Joshua D.; Bermudez, Yira; Park, Sophia L.; Stratton, Steven P.; Uchida, Koji; Hurst, Craig A.; Wondrak, Georg T.

    2014-01-01

    Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than three-fold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. PMID:24584085

  2. Ceftaroline fosamil in the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.

    PubMed

    Lodise, Thomas P; Low, Donald E

    2012-07-30

    Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. Because of its unique spectrum of activity, the Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline as a member of a new subclass of β-lactam antimicrobials, cephalosporins with anti-MRSA activity. The activity of ceftaroline against S. aureus extends to heteroresistant vancomycin-intermediate, vancomycin-intermediate, vancomycin-resistant and daptomycin-nonsusceptible isolates. Ceftaroline has low minimum inhibitory concentrations (MICs) for all tested species of streptococci, and has potent activity against S. pneumoniae isolates with varying degrees of penicillin resistance. The activity of ceftaroline is limited against Enterococcus faecalis and Enterococcus faecium and against anaerobes such as Bacteroides fragilis. The in vitro activity of ceftaroline includes many Gram-negative pathogens, but does not extend to bacteria that produce extended-spectrum β-lactamases, class B metallo-β-lactamases or AmpC cephalosporinases, or to most nonfermentative Gram-negative bacilli. Ceftaroline fosamil has been studied for the treatment of complicated skin and skin structure infections (cSSSI) and community-acquired pneumonia (CAP) in phase III randomized, double-blind, international, multicentre noninferiority clinical trials. Two identical trials (CANVAS 1 and CANVAS 2) compared the efficacy of ceftaroline fosamil with that of

  3. Mometasone Furoate Effect on Acute Skin Toxicity in Breast Cancer Patients Receiving Radiotherapy: A Phase III Double-Blind, Randomized Trial From the North Central Cancer Treatment Group N06C4

    SciTech Connect

    Miller, Robert C.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Stoffel, Thomas J.; Haselow, Robert E.; Schaefer, Paul L.; Bearden, James D.; Atherton, Pamela J.; Loprinzi, Charles L.; Martenson, James A.

    2011-04-01

    Purpose: A two-arm, double-blind, randomized trial was performed to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials: Patients with ductal carcinoma in situ or invasive breast carcinoma who were undergoing external beam radiotherapy to the breast or chest wall were randomly assigned to apply 0.1% MMF or placebo cream daily. The primary study endpoint was the provider-assessed maximal grade of Common Terminology Criteria for Adverse Events, version 3.0, radiation dermatitis. The secondary endpoints included provider-assessed Common Terminology Criteria for Adverse Events Grade 3 or greater radiation dermatitis and adverse event monitoring. The patient-reported outcome measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and a quality-of-life self-assessment. An assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results: A total of 176 patients were enrolled between September 21, 2007, and December 7, 2007. The provider-assessed primary endpoint showed no difference in the mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs. 1.3 for placebo; p = .18). Common Terminology Criteria for Adverse Events toxicity was greater in the placebo group (p = .04), primarily from pruritus. For the patient-reported outcome measures, the maximum Skindex-16 score for the MMF group showed less itching (p = .008), less irritation (p = .01), less symptom persistence or recurrence (p = .02), and less annoyance with skin problems (p = .04). The group's maximal Skin Toxicity Assessment Tool score showed less burning sensation (p = .02) and less itching (p = .002). Conclusion: Patients receiving daily MMF during radiotherapy might experience reduced acute skin toxicity compared with patients receiving placebo.

  4. Mometasone Furoate Effect on Acute Skin Toxicity in Breast Cancer Patients Receiving Radiotherapy: A Phase 3 Double-Blind, Randomized Trial from the North Central Cancer Treatment Group N06C4

    PubMed Central

    Miller, Robert C.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Stoffel, Thomas J.; Haselow, Robert E.; Schaefer, Paul L.; Bearden, James D.; Atherton, Pamela J.; Loprinzi, Charles L.; Martenson, James A.

    2010-01-01

    Purpose A 2-arm, double-blinded, randomized trial to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials Patients with ductal carcinoma in situ or invasive breast carcinoma receiving external beam radiotherapy to breast or chest wall were randomly assigned to daily apply 0.1% MMF or placebo cream. Primary study end point was provider-assessed maximum grade of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 radiation dermatitis. Secondary end points included provider-assessed CTCAE grade 3 or greater radiation dermatitis and adverse-event monitoring. Patient-reported outcome (PRO) measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and quality of life self-assessment. Assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results In total, 176 patients were enrolled from September 21, 2007 through December 7, 2007. The provider-assessed primary end point showed no difference in mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs 1.3 for placebo; P=.18). CTCAE toxicity was greater in placebo group (P=.04), primarily from pruritus. For PRO measures, the maximum Skindex-16 score for MMF group showed less itching (P=.008), less irritation (P=.01), less symptom persistence or recurrence (P=.02), and less annoyance with skin problems (P=.04); the group's maximum Skin Toxicity Assessment Tool score showed less burning sensation (P=.02) and less itching (P=.002). Conclusion Patients receiving daily MMF during radiotherapy may experience reduced acute skin toxicity in comparison to placebo. PMID:20800381

  5. In Vivo Assessment of Acute UVB Responses in Normal and Xeroderma Pigmentosum (XP-C) Skin-Humanized Mouse Models

    PubMed Central

    García, Marta; Llames, Sara; García, Eva; Meana, Alvaro; Cuadrado, Natividad; Recasens, Mar; Puig, Susana; Nagore, Eduardo; Illera, Nuria; Jorcano, José Luis; Del Rio, Marcela; Larcher, Fernando

    2010-01-01

    In vivo studies of UVB effects on human skin are precluded by ethical and technical arguments on volunteers and inconceivable in cancer-prone patients such as those affected with Xeroderma Pigmentosum (XP). Establishing reliable models to address mechanistic and therapeutic matters thus remains a challenge. Here we have used the skin-humanized mouse system that circumvents most current model constraints. We assessed the UVB radiation effects including the sequential changes after acute exposure with respect to timing, dosage, and the relationship between dose and degree-sort of epidermal alteration. On Caucasian-derived regenerated skins, UVB irradiation (800 J/m2) induced DNA damage (cyclobutane pyrimidine dimers) and p53 expression in exposed keratinocytes. Epidermal disorganization was observed at higher doses. In contrast, in African descent–derived regenerated skins, physiological hyperpigmentation prevented tissue alterations and DNA photolesions. The acute UVB effects seen in Caucasian-derived engrafted skins were also blocked by a physical sunscreen, demonstrating the suitability of the system for photoprotection studies. We also report the establishment of a photosensitive model through the transplantation of XP-C patient cells as part of a bioengineered skin. The inability of XP-C engrafted skin to remove DNA damaged cells was confirmed in vivo. Both the normal and XP-C versions of the skin-humanized mice proved proficient models to assess UVB-mediated DNA repair responses and provide a strong platform to test novel therapeutic strategies. PMID:20558577

  6. [Empirical therapeutic approach to infection by resistant gram positive (acute bacterial skin and skin structure infections and health care pneumonia). Value of risk factors].

    PubMed

    González-DelCastillo, J; Núñez-Orantos, M J; Candel, F J; Martín-Sánchez, F J

    2016-09-01

    Antibiotic treatment inadequacy is common in these sites of infection and may have implications for the patient's prognosis. In acute bacterial skin and skin structure infections, the document states that for the establishment of an adequate treatment it must be assessed the severity, the patient comorbidity and the risk factors for multidrug-resistant microorganism. The concept of health care-associated pneumonia is discussed and leads to errors in the etiologic diagnosis and therefore in the selection of antibiotic treatment. This paper discusses how to perform this approach to the possible etiology to guide empirical treatment.

  7. Fruit acids do not enhance sodium lauryl sulphate-induced cumulative irritant contact dermatitis in vivo.

    PubMed

    Schliemann-Willers, Sibylle; Fuchs, Silke; Kleesz, Peter; Grieshaber, Romano; Elsner, Peter

    2005-01-01

    Combined exposure to different irritants in the workplace may lead to irritant contact dermatitis, which is the main type of occupational dermatitis among bakers and confectioners. Following previous work on "tandem irritation", a panel of healthy volunteers was exposed twice daily for 4 days to the organic fruit acids: citric, malic, and lactic acid, either alone or in tandem application with 0.5% sodium lauryl sulphate (SLS) in a repetitive irritation test. Irritant cutaneous reactions were quantified by visual scoring and non-invasive measurement of transepidermal water loss and skin colour reflectance. Twice daily application of either citric or malic acid alone did not induce a significant irritant reaction. Combined exposure to one of the fruit acids and SLS caused marked barrier disturbance, but the latter irritant effect was smaller than that obtained by combined exposure to SLS and water. Thus, combined exposure to the above-mentioned fruit acids and SLS did not enhance cumulative skin irritation.

  8. Fussy or irritable child

    MedlinePlus

    ... Ask questions and take a history Examine your child Order lab tests, if needed Alternative Names Inconsolability; irritability Images Central nervous system and peripheral nervous system References ...

  9. Evaluation of calcium magnesium acetate and road salt for contact hypersensitivity potential and dermal irritancy in humans.

    PubMed

    Cushman, J R; Duff, V A; Buteau, G H; Aust, L B; Caldwell, N; Lazer, W

    1991-04-01

    Calcium magnesium acetate (CMA) and road salt are both de-icing agents to which workers may be dermally exposed. A commercial formulation of CMA (Chevron Ice-B-Gon Deicer) and road salt were tested in a human repeat insult patch test to evaluate the contact hypersensitivity potential of these materials and to evaluate irritation following single or multiple applications. 72 of the initial 82 panelists completed the study. CMA and road salt (each at 10% and 30% w/w in distilled water; 0.3 ml) were administered under occlusive patches on the forearm for 14 h 3 x per week for 3 weeks. The panelists were challenged 2 weeks later; 2 panelists who had mild reactions were subsequently rechallenged 6 weeks later. Neither CMA nor road salt produced contact hypersensitivity in any panelists. Following the first application, moderate acute irritation was observed only at 1 skin site exposed to 30% road salt. Repeated exposure to CMA or road salt produced mild to moderate irritation. The highest incidence of moderate irritation was observed with 30% road salt. Thus, neither material is expected to cause significant dermal effects in exposed workers. CMA is expected to cause dermal irritation equivalent to or less than that caused by road salt.

  10. Impact of Antimicrobial Stewardship Program (ASP) on Outcomes in Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) in an Acute-Tertiary Care Hospital.

    PubMed

    Loo, Li Wen; Liew, Yi Xin; Lee, Winnie; Chlebicki, Piotr; Kwa, Andrea Lay-Hoon

    2015-09-01

    Acute bacterial skin and skin structure infections (ABSSSIs) are among the most common infections treated in hospitals, but to date, there has been little information with regards to the implementation of Antimicrobial Stewardship Programs (ASPs) for patients with ABSSSIs. Hence, we aim to evaluate the impact of ASPs on the following outcomes in patients with ABSSSIs: duration of therapy and hospital stay, 14-day reinfection, infection-related readmissions and mortality. A retrospective review of the ASP database was conducted, focusing on selected outcomes (as above) among all patients in whom the institution's ASP recommended a change in antibiotic regimen-de-escalation of the antibiotic based on culture results; discontinuation of the antibiotic; narrowing of the empirical coverage; and intravenous-to-oral (i.v.-to-p.o.) switch between September 2009 and December 2012. Data were expressed as mean ± standard deviation for continuous variables, and unpaired Student's t test was performed to determine intergroup differences between mean values. For categorical variables, data were presented as number and percentage and analyzed using the χ (2) test or Fisher's exact test, as appropriate. ASP recommended 407 interventions with an overall acceptance rate of 66.8%. ASP interventions significantly reduced median duration of therapy by 2 [from a median (interquartile range, IQR) of 8 (6-12) days to 6 (4-9) days] and median length of stay by 5 days [from median (IQR) of 12 (5-32) days to 7 (3-18) days]. This led to an estimated total cost avoidance of USD 0.7 million. There were no significant differences in the 14-day reinfection, infection-related readmission and mortality rates between patients whose physicians accepted and those who rejected ASP interventions. Interventions recommended by the ASP in Singapore General Hospital were safe and associated with a significant reduction in duration of therapy and hospital stay. The results of our study have affirmed

  11. Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms.

    PubMed

    Stanhewicz, Anna E; Alexander, Lacy M; Kenney, W Larry

    2013-10-01

    Functional constitutive nitric oxide synthase (NOS) and its cofactor tetrahydrobiopterin (BH4) are required for full reflex cutaneous vasodilation and are attenuated in primary aging. Acute, locally administered BH4 increases reflex vasodilation through NO-dependent mechanisms in aged skin. We hypothesized that oral sapropterin (Kuvan, shelf-stable pharmaceutical formulation of BH4) would augment reflex vasodilation in aged human skin during hyperthermia. Nine healthy human subjects (76 ± 1 yr) ingested sapropterin (10 mg/kg) or placebo in a randomized double-blind crossover design. Venous blood samples were collected prior to, and 3 h following, ingestion of sapropterin for measurement of plasma BH4. Three intradermal microdialysis fibers were placed in the forearm skin for local delivery of 1) lactated Ringer's solution, 2) 10 mM BH4, and 3) 20 mM N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) as reflex vasodilation was induced using a water-perfused suit. At 1°C rise in oral temperature, mean body temperature was clamped and 20 mM l-NAME was perfused at each site. Cutaneous vascular conductance was calculated (CVC = LDF/MAP) and expressed as a percentage of maximum (%CVCmax 28 mM sodium nitroprusside and local heat 43°C). Plasma concentrations of BH4 were significantly elevated 3 h after ingestion of sapropterin (0 h: 19.1 ± 2 pmol/ml vs. 3 h: 43.8 ± 3 pmol/ml; P < 0.001). Sapropterin increased NO-dependent vasodilation at control site (placebo: 14 ± 1 %CVCmax vs. sapropterin: 25 ± 4 %CVCmax; P = 0.004). Local BH4 administration increased NO-dependent vasodilation compared with control in placebo trials only (control: 14 ± 1 %CVCmax vs. BH4-treated: 24 ± 3 %CVCmax; P = 0.02). These data suggest oral sapropterin increases bioavailable BH4 in aged skin microvasculature sufficiently to increase NO synthesis through NOS and that sapropterin may be a viable intervention to

  12. Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms

    PubMed Central

    Stanhewicz, Anna E.; Kenney, W. Larry

    2013-01-01

    Functional constitutive nitric oxide synthase (NOS) and its cofactor tetrahydrobiopterin (BH4) are required for full reflex cutaneous vasodilation and are attenuated in primary aging. Acute, locally administered BH4 increases reflex vasodilation through NO-dependent mechanisms in aged skin. We hypothesized that oral sapropterin (Kuvan, shelf-stable pharmaceutical formulation of BH4) would augment reflex vasodilation in aged human skin during hyperthermia. Nine healthy human subjects (76 ± 1 yr) ingested sapropterin (10 mg/kg) or placebo in a randomized double-blind crossover design. Venous blood samples were collected prior to, and 3 h following, ingestion of sapropterin for measurement of plasma BH4. Three intradermal microdialysis fibers were placed in the forearm skin for local delivery of 1) lactated Ringer's solution, 2) 10 mM BH4, and 3) 20 mM NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF) as reflex vasodilation was induced using a water-perfused suit. At 1°C rise in oral temperature, mean body temperature was clamped and 20 mM l-NAME was perfused at each site. Cutaneous vascular conductance was calculated (CVC = LDF/MAP) and expressed as a percentage of maximum (%CVCmax 28 mM sodium nitroprusside and local heat 43°C). Plasma concentrations of BH4 were significantly elevated 3 h after ingestion of sapropterin (0 h: 19.1 ± 2 pmol/ml vs. 3 h: 43.8 ± 3 pmol/ml; P < 0.001). Sapropterin increased NO-dependent vasodilation at control site (placebo: 14 ± 1 %CVCmax vs. sapropterin: 25 ± 4 %CVCmax; P = 0.004). Local BH4 administration increased NO-dependent vasodilation compared with control in placebo trials only (control: 14 ± 1 %CVCmax vs. BH4-treated: 24 ± 3 %CVCmax; P = 0.02). These data suggest oral sapropterin increases bioavailable BH4 in aged skin microvasculature sufficiently to increase NO synthesis through NOS and that sapropterin may be a viable intervention to

  13. Proretinal nanoparticles: stability, release, efficacy, and irritation

    PubMed Central

    Pisetpackdeekul, Pimolphan; Supmuang, Piyapan; Pan-In, Porntip; Banlunara, Wijit; Limcharoen, Benchaphorn; Kokpol, Chayada; Wanichwecharungruang, Supason

    2016-01-01

    Despite many potent biological activities, retinoids such as retinoic acid (RA) and retinal possess dose-related broad side effects. In this study, we show that this problem, which has been unsolvable for a long time, can be tackled through a controlled release strategy in which retinal is continuously delivered to the skin via sustained release from proretinal nanoparticles. The water dispersible proretinal nanoparticles are stable when kept in water at neutral pH and at room temperature for 8 months under light-proof conditions, and show sustained release of retinal into human synthetic sebum at a pH of 5. In the daily topical application tests performed for 4 weeks on rats’ skin, the nanoparticles showed superior ability to increase epidermal thickness compared to RA and retinal, with no skin irritation observed for the proretinal particles, but severe skin irritation observed for RA and free retinal. When tested under occlusion conditions in human volunteers, insignificant skin irritation was observed for the proretinal nanoparticles. The 12-week, double-blind, split-face study on human volunteers indicates better antiaging efficacy of the particles as compared to the free RA. PMID:27499622

  14. The chamber-scarification test for irritancy.

    PubMed

    Frosch, P J; Kligman, A M

    1976-12-01

    A procedure has been designed (the chamber-scarification test), which possesses greatly increased sensitivity for assessing the irritancy of topically applied materials. A forearm test site is criss-cross scarified by drawing a 30-gauge needle over the skin with just enough pressure to cleave the epidermis without drawing blood. The test agent is applied in an aluminum chamber once daily for 3 days. The advantages of the method over conventional patch testing are: enhanced capacity to measure mild irritants, reduced time (3 days versus 10 to 21 days), less effort, less cost, less discomfort for the volunteers and greater reproducibility.

  15. Oily skin

    MedlinePlus

    ... Clean your face with astringent pads if frequent face washing causes irritation. Use only water-based or oil-free cosmetics if you have oily skin. Your health care provider may also recommend or prescribe creams to absorb or limit the production of oil ...

  16. Chronic, irritant contact dermatitis: Mechanisms, variables, and differentiation from other forms of contact dermatitis

    SciTech Connect

    Dahl, M.V. )

    1988-01-01

    Irritant dermatitis is an eczematous reaction to toxic chemicals contacting the skin. The mechanisms by which various chemicals elicit dermatitis are multiple. Strong irritants quickly elicit signs and symptoms of dermatitis, but weak irritants may not. Chronic cumulative exposure to weak irritants can elicit dermatitis which may mimic allergic contact dermatitis and mislead the physician and patient with respect to cause and preventative strategy. The skins of different people vary in susceptibilities to irritation. Susceptibility is also influenced by chemical properties, vehicles, concentrations, amounts applied to the skin surface, surface area, regional variations, length of exposure, method of exposure, age, sex, race, genetic background, environmental factors, hardening, concomitant disease, and the excited skin syndrome as well as treatment. Patch testing can help distinguish between allergens and irritants, but pitfalls may mislead.35 references.

  17. Modified skin window technique for the extended characterisation of acute inflammation in humans

    PubMed Central

    Marks, D. J. B.; Radulovic, M.; McCartney, S.; Bloom, S.; Segal, A. W.

    2009-01-01

    Objective To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease. Subjects 15 healthy subjects and 5 Crohn’s patients. Treatment Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide (MDP) or 10 μg/ml interleukin-8 (IL-8). Methods Exuded leukocytes were analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT-PCR. Inflammatory mediators were quantified by ELISA. Results Infiltrating leukocytes were predominantly neutrophils. Numerous secreted mediators were detectable. MDP and IL-8 enhanced responses. Many signalling proteins were phosphorylated with differential patterns in Crohn’s patients, notably PKC α/β hyperphosphorylation (11.3 ± 3.1 vs 1.2 ± 0.9 units, P < 0.02). Activities of 44 transcription factors were detectable, and sufficient RNA isolated for expression analysis of over 400 genes. Conclusions The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators. PMID:17522815

  18. 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.,…

  19. Irritable Bowel Syndrome

    MedlinePlus

    ... your belly area), constipation (when you can't poop), and diarrhea (when you poop too much). If you have irritable bowel syndrome, ... food particles are also known as stool, a bowel movement, or poop. Here's why an intestine gets "irritable." ...

  20. Acute skin trauma induces hyperemia, but superficial papillary nutritive perfusion remains unchanged.

    PubMed

    Sundheim, Liv Kristin; Sporastøyl, Ane Halse; Wester, Torjus; Salerud, Göran; Kvernebo, Knut

    2017-10-01

    Superficial skin papillary capillaries with blood supply from a superficial vascular plexus and regulated by local metabolic needs supply oxygen and nutrients for epithelial cell proliferation. A deep vascular plexus regulated by autonomous nerves serves body thermoregulation. In healthy volunteers, we assessed circulatory effects of a standardized skin trauma by CAVM, DRS, and LDPM to assess the measuring depth of the three techniques and to describe the acute trauma effects on nutritive and thermoregulatory perfusion. Volunteers (n=12) were examined at baseline and after induction of a 5.0 mm×1.0 mm incision on the forearm; 30 minutes after the trauma induction, data were collected at 0-1, 2-3 and 30 mm distances. LDPM showed hyperemia at 2-3 mm distance (35.8±15.2 a.u.), but not at 30 mm distance (7.4±2.5 a.u.) compared to baseline (8.8±1.8 a.u.). The DRS saturation increased at 2-3 mm (71.2±4.8%), but not at 30 mm (49.8±7.9%) compared to baseline (45.8±7.4%). Capillary density and flow velocities were unaffected at all distances. The results indicate that skin nutritive papillary capillary function can be assessed by CAVM and DRS, but not with LDPM because of its dependence of the deep plexus perfusion. © 2017 John Wiley & Sons Ltd.

  1. 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.

  2. Efficacy of a skin tear education program: improving the knowledge of nurses practicing in acute care settings.

    PubMed

    McTigue, Toni; D'Andrea, Stephanie; Doyle-Munoz, Janet; Forrester, D Anthony

    2009-01-01

    We sought to evaluate the knowledge base of acute care registered nurses (RNs) regarding skin tears and the efficacy of an online educational program designed to improve their knowledge of skin tears including (1) predisposing factors; (2) identification and assessment of skin tears using the Payne-Martin Classification System; and (3) preventive care, treatment, and documentation. This was a prospective quasi-experimental education intervention study. Four hundred sixteen acute care RNs from 2 affiliated hospitals participated in the study. They comprised approximately 20% of more than 2,000 nurses employed by Atlantic Health. These nurses worked in critical care, medical-surgical, and specialty units and varied in age, level of education, work experience, and years in nursing. A Web-based educational program was provided for over 4 months on our intranet service, which was available to all RN staff 24-hours-a-day, 7-days-a-week. The educational program was subdivided into 3 sections: (1) identification and assessment, (2) classification and differentiation, and (3) treatment. Nurses' knowledge of skin tears improved following the Web-based educational program. Following completion of the identification and assessment of skin tears section, participants were better able to identify and correctly assess skin tears (mean scores 99.1% vs 97.1%, P < .001). Participants also achieved greater knowledge of the differentiation between categories I, II, and III skin tears (mean scores 94.9% vs 83.4%, P < .001) and knowledge of treatment (mean score 93.7% vs 73.8%, P < .001). Our Web-based skin tear educational program was effective in improving nurses' knowledge regarding skin tear identification and assessment, classification and differentiation, and treatment.

  3. The Cutaneous Microbiome and Aspects of Skin Antimicrobial Defense System Resist Acute Treatment with Topical Skin Cleansers.

    PubMed

    Two, Aimee M; Nakatsuji, Teruaki; Kotol, Paul F; Arvanitidou, Evangelia; Du-Thumm, Laurence; Hata, Tissa R; Gallo, Richard L

    2016-10-01

    The human skin microbiome has been suggested to play an essential role in maintaining health by contributing to innate defense of the skin. These observations have inspired speculation that the use of common skin washing techniques may be detrimental to the epidermal antibacterial defense system by altering the microbiome. In this study, several common skin cleansers were used to wash human forearms and the short-term effect on the abundance of the antimicrobial peptide LL-37 and the abundance and diversity of bacterial DNA was measured. Despite small but significant decreases in the amount of LL-37 on the skin surface shortly after washing, no significant change in the bacterial community was detected. Furthermore, Group A Streptococcus did not survive better on the skin after washing. In contrast, the addition of antimicrobial compounds such as benzalkonium chloride or triclocarban to soap before washing decreased the growth of Group A Streptococcus applied after rinse. These results support prior studies that hand washing techniques in the health care setting are beneficial and should be continued. Additional research is necessary to better understand the effects of chronic washing and the potential impact of skin care products on the development of dysbiosis in some individuals. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Irritantcy potential and sub acute dermal toxicity study of Pistacia lentiscus fatty oil as a topical traditional remedy.

    PubMed

    Djerrou, Zouhir; Djaalab, Hdria; Riachi, Foulla; Serakta, Mennouba; Chettoum, Aziez; Maameri, Zineb; Boutobza, Badaoui; Hamdi-Pacha, Youcef

    2013-01-01

    The current study was undertaken to assess safety of Pistacia lentiscus fruits fatty oil (PLFO) as a topical traditional remedy. A primary skin and eye irritation tests were conducted with New Zealand white rabbits to determine the potential for PLFO to produce irritation from a single application. In addition, a sub acute dermal toxicity study was performed on 18 NZW rabbits to evaluate possible adverse effect following application of PLFO for 28 days. Based on the results of the current study, PLFO is classified as slightly irritating to the skin and the eye of rabbits (Primary Irritation Index (P.I.I.) = 1.037; Ocular Irritation Index (O.I.I.) = 5.33 at 1 h). In the sub-acute toxicity test, PLFO produced neither mortality nor significant differences in the body and organ weights between control group and treated rabbits. However, a reversible irritant contact dermatitis was observed in the treated areas from the end of the second week of application until the end of experiment. This local phenomenon was accompanied by a significant skin thickening (P≤0.01) since the 12(th) day (ANOVA, F = 11, 07143, P = 0, 00765) which is confirmed with an inflammatory granuloma in histological study. Haematological analysis and blood chemistry values of the 2 groups showed no significant differences in any of the parameters examined. In summary, PLFO is minimally irritating to the eye and skin after a single exposure, but it may cause irritant contact dermatitis and a reversible thickening of skin after prolonged use.

  5. Dose-surface analysis for prediction of severe acute radio-induced skin toxicity in breast cancer patients.

    PubMed

    Pastore, Francesco; Conson, Manuel; D'Avino, Vittoria; Palma, Giuseppe; Liuzzi, Raffaele; Solla, Raffaele; Farella, Antonio; Salvatore, Marco; Cella, Laura; Pacelli, Roberto

    2016-01-01

    Severe acute radiation-induced skin toxicity (RIST) after breast irradiation is a side effect impacting the quality of life in breast cancer (BC) patients. The aim of the present study was to develop normal tissue complication probability (NTCP) models of severe acute RIST in BC patients. We evaluated 140 consecutive BC patients undergoing conventional three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery in a prospective study assessing acute RIST. The acute RIST was classified according to the RTOG scoring system. Dose-surface histograms (DSHs) of the body structure in the breast region were extracted as representative of skin irradiation. Patient, disease, and treatment-related characteristics were analyzed along with DSHs. NTCP modeling by Lyman-Kutcher-Burman (LKB) and by multivariate logistic regression using bootstrap resampling techniques was performed. Models were evaluated by Spearman's Rs coefficient and ROC area. By the end of radiotherapy, 139 (99%) patients developed any degree of acute RIST. G3 RIST was found in 11 of 140 (8%) patients. Mild-moderate (G1-G2) RIST was still present at 40 days after treatment in six (4%) patients. Using DSHs for LKB modeling of acute RIST severity (RTOG G3 vs. G0-2), parameter estimates were TD50=39 Gy, n=0.38 and m=0.14 [Rs = 0.25, area under the curve (AUC) = 0.77, p = 0.003]. On multivariate analysis, the most predictive model of acute RIST severity was a two-variable model including the skin receiving ≥30 Gy (S30) and psoriasis [Rs = 0.32, AUC = 0.84, p < 0.001]. Using body DSH as representative of skin dose, the LKB n parameter was consistent with a surface effect for the skin. A good prediction performance was obtained using a data-driven multivariate model including S30 and a pre-existing skin disease (psoriasis) as a clinical factor.

  6. Bioassays to evaluate non-contact spatial repellency, contact irritancy, and acute toxicity of permethrin-treated clothing against nymphal Ixodes scapularis ticks.

    PubMed

    Eisen, Lars; Rose, Dominic; Prose, Robert; Breuner, Nicole E; Dolan, Marc C; Thompson, Karen; Connally, Neeta

    2017-10-01

    Summer-weight clothing articles impregnated with permethrin are available as a personal protective measure against human-biting ticks in the United States. However, very few studies have addressed the impact of contact with summer-weight permethrin-treated textiles on tick vigor and behavior. Our aim was to generate new knowledge of how permethrin-treated textiles impact nymphal Ixodes scapularis ticks, the primary vectors in the eastern United States of the causative agents of Lyme disease, human anaplasmosis, and human babesiosis. We developed a series of bioassays designed to: (i) clarify whether permethrin-treated textiles impact ticks through non-contact spatial repellency or contact irritancy; (ii) evaluate the ability of ticks to remain in contact with vertically oriented permethrin-treated textiles, mimicking contact with treated clothing on arms or legs; and (iii) determine the impact of timed exposure to permethrin-treated textiles on the ability of ticks to move and orient toward a human finger stimulus, thus demonstrating normal behavior. Our results indicate that permethrin-treated textiles provide minimal non-contact spatial repellency but strong contact irritancy against ticks, manifesting as a "hot-foot" effect and resulting in ticks actively dislodging from contact with vertically oriented treated textile. Preliminary data suggest that the contact irritancy hot-foot response may be weaker for field-collected nymphs as compared with laboratory-reared nymphs placed upon permethrin-treated textile. We also demonstrate that contact with permethrin-treated textiles negatively impacts the vigor and behavior of nymphal ticks for >24h, with outcomes ranging from complete lack of movement to impaired movement and unwillingness of ticks displaying normal movement to ascend onto a human finger. The protective effect of summer-weight permethrin-treated clothing against tick bites merits further study. Published by Elsevier GmbH.

  7. Correlation between anthropometric parameters and acute skin toxicity in breast cancer radiotherapy patients: a pilot assessment study.

    PubMed

    Méry, Benoîte; Vallard, Alexis; Trone, Jane-Chloé; Pacaut, Cécile; Guy, Jean-Baptiste; Espenel, Sophie; Langrand-Escure, Julien; Ollier, Edouard; Wang, Guoping; Diao, Peng; Bigot, Lise; Mengue Ndong, Sylvie; Bosacki, Claire; Ben Mrad, Majed; Magné, Nicolas

    2015-01-01

    The objective of the present study was to identify acute skin toxicity risk factors linked to the anthropometric characteristics of patients with breast cancer treated with radiation therapy. Consecutive patients with breast cancer were enrolled after breast-conserving surgery and before radiotherapy course. Acute skin toxicity was assessed weekly during the 7 weeks of radiotherapy with the International Classification from National Cancer Institute. Grade 2 defined acute skin toxicity. Patient characteristics and anthropometric measurements were collected. 54 patients were enrolled in 2013. Eight patients (14.8%) had grade ≥2 toxicity. The average weight and chest size were 65.5 kg and 93.6 cm, respectively. Bra cup size is significantly associated with a risk of grade 2 dermatitis [odds ratio (OR) 3.46, 95% confidence interval (CI) (1.29-11.92), p = 0.02]. Anthropometric breast fat mass measurements, such as thickness of left [OR 2.72, 95% CI (1.08-8.26), p = 0.04] and right [OR 2.45, 95% CI (0.99-7.27), p = 0.05] axillary fat, are correlated with an increased risk. Distance between the pectoral muscle and nipple is a reproducible measurement of breast size and is associated with acute skin toxicity with significant tendency (OR = 2.21, 95% CI (0.97-5.98), p = 0.07). Breast size and its different anthropometric measurements (thickness of left and right axillary fat, nipple-to-pectoral muscle distance) are correlated with the risk of skin toxicity. The present article analyses several characteristics and anthropomorphic measurements of breast in order to assess breast size. A standardized and reproducible protocol to measure breast volume is described.

  8. Novel protective agent GF-6 for skin wounds.

    PubMed

    Mulkijanyan, K; Novikova, J; Sulakvelidze, M

    2010-09-01

    The aim of present investigation was the determination of specific pharmacological (wound healing) properties and the evaluation of possible irritative, allergenic and toxic effects of GF-6 - novel protective agent for skin mechanical and burn wounds. In mouse excisional wound model GF-6 (topically 0.1 ml per wound) exhibited the ability to accelerate scab rejection and full reepithelization in test wounds with no signs of bacterial contamination. GF-6 caused no irritation responses such as erythema, oedema, dotted hemorrhage, hyperkeratosis, hyperplasia, alopecia and scaling in 14-day acute dermal irritation test. As well no signs of skin hypersensitivity (itch, erythema, oedema), and histological alteration (ulceration, dotted hemorrhage, changed capillary lumen, damaged hair follicle) were observed in skin application test at all time points during the 14-day observation period, evidencing that GF-6 is non-allergenic. In subchronic dermal toxicity 90-day study of five-fold concentrated GF-6 no statistically significant changes in respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behavior patterns were detected. The results of hematological study testified to no influence of the GF-6 90-day application on blood formed elements. Thus, GF-6 should be considered non-toxic, non-irritant, non-allergenic wound healing and wound protecting agent.

  9. Telavancin for Acute Bacterial Skin and Skin Structure Infections, a Post Hoc Analysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance

    PubMed Central

    Pushkin, Richard; Barriere, Steven L.; Corey, G. Ralph; Stryjewski, Martin E.

    2015-01-01

    Two phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections. Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections. This post hoc analysis included patients with lesion sizes of ≥75 cm2 and excluded patients with ulcers or burns (updated all-treated population; n = 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic. Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures. Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of −4.0% to 7.4%). Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, −0.7% to 10.3%). Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin. PMID:26248356

  10. Telavancin for Acute Bacterial Skin and Skin Structure Infections, a Post Hoc Analysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance.

    PubMed

    Pushkin, Richard; Barriere, Steven L; Wang, Whedy; Corey, G Ralph; Stryjewski, Martin E

    2015-10-01

    Two phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections. Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections. This post hoc analysis included patients with lesion sizes of ≥75 cm(2) and excluded patients with ulcers or burns (updated all-treated population; n = 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic. Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures. Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of -4.0% to 7.4%). Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, -0.7% to 10.3%). Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin.

  11. 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 ...

  12. Characterisation of leukocytes in a human skin blister model of acute inflammation and resolution.

    PubMed

    Jenner, William; Motwani, Madhur; Veighey, Kristin; Newson, Justine; Audzevich, Tatsiana; Nicolaou, Anna; Murphy, Sharon; Macallister, Raymond; Gilroy, Derek W

    2014-01-01

    There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies.

  13. Characterisation of Leukocytes in a Human Skin Blister Model of Acute Inflammation and Resolution

    PubMed Central

    Veighey, Kristin; Newson, Justine; Audzevich, Tatsiana; Nicolaou, Anna; Murphy, Sharon; MacAllister, Raymond; Gilroy, Derek W.

    2014-01-01

    There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies. PMID:24603711

  14. Specific skin manifestations in acute leukemia with monocytic differentiation. A morphologic and immunohistochemical study of 11 cases.

    PubMed

    Sepp, N; Radaszkiewicz, T; Meijer, C J; Smolle, J; Seewann, H; Fritsch, P; Kerl, H

    1993-01-01

    Monocytic differentiation is present in the myelomonocytic (M4) and monocytic (M5) type of acute myeloblastic leukemia. Infiltration of the skin in acute myelomonocytic leukemia occurs in 10-20% of patients, the skin lesions occasionally being the first symptom, even preceding monocytosis. Eleven patients with myelomonocytic (n = 2) and monocytic leukemia (n = 9) were studied who had skin manifestations. Clinically, all patients showed disseminated papules or nodules that corresponded histologically to nodular or diffuse infiltrates of monocytoid cells, occasionally displaying a whorled pattern. The currently available antibodies for paraffin-embedded sections (lysozyme, elastase, leukocyte common antigen (CD45), MT1 (CD43), Leu-M1 (CD15), LN2 (CD74), MB2, MB1 (CD45RA), LN1 (w75), Mac387, L26 (CD20), UCHL1 (CDR0), MT2 (CD45RA), and KP-1 (CD68)) and chloracetate-esterase are not more helpful in diagnosis than are the histologic findings. By contrast, the antibodies used on frozen sections (Leu-4 (CD3), Leu-3a (CD4), BA1 (CD24), B4 (CD19), Leu-M5 (CD11c), Vim12 (CD11b), VimD5 (CD15), KiM6 (CD68), KIM7 (CD68), My7 (CD13), and My9 (CD33) allow the definition of a reaction pattern that is diagnostic for acute myeloid leukemia with monocytic differentiation.

  15. Sensitive skin: an overview.

    PubMed

    Berardesca, E; Farage, M; Maibach, H

    2013-02-01

    Sensitive skin is a condition of subjective cutaneous hyper-reactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sun screens, and they often report worsening after exposure to dry and cold climate. Although no sign of irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present. Generally substances that are not commonly considered irritants are involved in this abnormal response.Sensitive skin and subjective irritation are widespread but still far from being completely defined and understood. A correlation between sensitive skin and constitutional anomalies and/or other triggering factors such as occupational skin diseases or chronic exposure to irritants has been hypothesized. Recent findings suggest that higher sensitivity can be due to different mechanisms. Hyper-reactors may have a thinner stratum corneum with a reduced corneocyte area causing a higher transcutaneous penetration of water-soluble chemicals. Alterations in vanilloid receptors and changes in neuronal transmission have been described. Monitoring skin parameters such as barrier function, proclivity to irritation, corneocyte size and sensorial transmission can also be useful to identify regional differences in skin sensitivity.

  16. Comprehensive Evaluation of Personal, Clinical, and Radiation Dosimetric Parameters for Acute Skin Reaction during Whole Breast Radiotherapy

    PubMed Central

    Yang, Dae Sik; Lee, Jung Ae; Lee, Nam Kwon; Park, Young Je; Lee, Suk; Kim, Chul Yong; Son, Gil Soo

    2016-01-01

    Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The V100 (volume receiving 100% of prescribed radiation dose, p < 0.001, both axilla and inferior fold) and age (p = 0.039 for axilla and 0.026 for inferior fold) were significant parameters in multivariate analyses. The calculated axilla dose (p = 0.003) and breast separation (p = 0.036) were also risk factors for axilla and inferior fold, respectively. Young age and large V100 are significant factors for acute skin reaction that can be simply and cost-effectively measured. PMID:27579310

  17. Comprehensive Evaluation of Personal, Clinical, and Radiation Dosimetric Parameters for Acute Skin Reaction during Whole Breast Radiotherapy.

    PubMed

    Yang, Dae Sik; Lee, Jung Ae; Yoon, Won Sup; Lee, Nam Kwon; Park, Young Je; Lee, Suk; Kim, Chul Yong; Son, Gil Soo

    2016-01-01

    Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The V 100 (volume receiving 100% of prescribed radiation dose, p < 0.001, both axilla and inferior fold) and age (p = 0.039 for axilla and 0.026 for inferior fold) were significant parameters in multivariate analyses. The calculated axilla dose (p = 0.003) and breast separation (p = 0.036) were also risk factors for axilla and inferior fold, respectively. Young age and large V 100 are significant factors for acute skin reaction that can be simply and cost-effectively measured.

  18. Skin conductance for monitoring of acute pain in adult postoperative patients: influence of electrode surface area and sampling time.

    PubMed

    Ledowski, Thomas; Albus, Sebastian; Stein, Jessica; Macdonald, Bradley

    2011-12-01

    Aim of this prospective randomized study was to determine the influence of the electrode surface area and sampling time on the accuracy of the number of fluctuations in skin conductance per second to distinguish different states of acute pain. These methodological issues have been previously suggested as an explanation for contradictory data related to the accuracy of the skin conductance monitor. A total of 541 pain ratings on a numeric rating scale (0-10) were obtained from 120 adult postoperative patients. The number of fluctuations in skin conductance per second was recorded using two different electrode types (surface area 254 vs. 474 mm(2)) and sampling times (7.5 vs. 30 s). A longer sampling time did result in higher values for the number of fluctuations in skin conductance per second, though without improving its accuracy to distinguish different states of pain. However, the latter was found improved when the smaller surface area electrodes were used. A combination of small surface area electrodes and a 30 s sampling time resulted in the highest area under the curve in the receiver operating curve analysis of the method to identify states of moderate to severe pain (numeric rating scale > 3): 0.68 vs. e.g. 0.55 [data from all patients combined]). We conclude that the type of electrodes used but only to a lesser degree the sampling time influence the accuracy of the number of fluctuations in skin conductance per second to identify states of moderate or severe postoperative pain.

  19. Evaluation of lotion formulations on irritation using the modified forearm-controlled application test method.

    PubMed

    Farage, M A; Ebrahimpour, A; Steimle, B; Englehart, J; Smith, D

    2007-08-01

    Cold and allergy sufferers often develop irritation around the nostrils as a result of repeated and frequent rubbing of the skin site with facial tissues. This irritation is a combination of the inherent irritant properties of the tissue components (chemical irritation), and mechanical irritation from friction. Lotion-coated facial tissues are being developed to provide soothing, skin benefits, and to promote healing of this type of irritation. The objective of these studies was to evaluate the efficacy of different lotion formulations on facial tissues in preventing irritation, or aiding in the healing of irritation. The modified forearm-controlled application test (Modified FCAT) was adapted as a means of quickly evaluating the relative skin benefits of various lotion formulations used to coat facial tissues. The test was conducted on the volar surface of the forearms of volunteer subjects. Test sites were pretreated with 24 h occlusive patches of sodium lauryl sulfate (SLS) to induce mild or moderate skin irritation. This was followed by repeated wiping of the lotion-coated tissues. Irritation was evaluated using visual scoring for erythema and dryness. Lotion formulation options were compared in the model. Comparisons included assessments of the type of fatty alcohol in the formulation (stearyl and cetearyl alcohol), the presence of silicone and the base formulation (mineral oil, petrolatum of a proprietary formula). Differences in the degree of erythema and dryness were detected among various formulation options. No differences were found between formulations containing stearyl or cetearyl alcohol. Low levels of silicone produced benefits in one of two experiments. The proprietary base formula produced greater reductions in erythema following treatment of SLS-irritated skin compared with mineral oil and petrolatum bases. The results indicated that this modification of the FCAT can be used to compare various lotion formulations for skin benefits and healing

  20. Use of Axillary Deodorant and Effect on Acute Skin Toxicity During Radiotherapy for Breast Cancer: A Prospective Randomized Noninferiority Trial

    SciTech Connect

    Theberge, Valerie; Harel, Francois; Dagnault, Anne

    2009-11-15

    Purpose: To prospectively determine the effect of deodorant use on acute skin toxicity and quality of life during breast radiotherapy (RT). Methods and Materials: Before breast RT, 84 patients were randomly assigned to the deodorant group (n = 40) or the no-deodorant group (n = 44). The patients were stratified by axillary RT and previous chemotherapy. Toxicity evaluations were always performed by the principal investigator, who was unaware of the group assignment, at the end of RT and 2 weeks after completion using the Radiation Therapy Oncology Group acute skin toxicity criteria. Symptoms of acute skin toxicity (i.e., discomfort, pain, pruritus, sweating) and quality of life were self-evaluated. For each criterion, the point estimate of rate difference with the 95% one-sided upper confidence limit was computed. To claim noninferiority owing to deodorant use, the 95% one-sided upper confidence limit had to be lower than the noninferiority margin, fixed to 12.8%. Results: In the deodorant vs. no-deodorant groups, Grade 2 axillary radiodermatitis occurred in 23% vs. 30%, respectively, satisfying the statistical criteria for noninferiority (p = .019). Grade 2 breast radiodermatitis occurred in 30% vs. 34% of the deodorant vs. no-deodorant groups, respectively, also satisfying the statistical criteria for noninferiority (p = .049). Similar results were observed for the self-reported evaluations. The deodorant group reported less sweating (18% vs. 39%, p = .032). No Grade 3 or 4 radiodermatitis was observed. Conclusion: According to our noninferiority margin definition, the occurrence of skin toxicity and its related symptoms were statistically equivalent in both groups. No evidence was found to prohibit deodorant use (notwithstanding the use of an antiperspirant with aluminum) during RT for breast cancer.

  1. Safety evaluation of perfluoropolyethers, liquid polymers used in barrier creams and other skin-care products.

    PubMed

    Malinverno, G; Pantini, G; Bootman, J

    1996-07-01

    Fomblin HC products are a 'family' of high-purity perfluoropolyethers manufactured for barrier cream and other personal care applications which involve direct application to the skin. To confirm the safety of such use, representative Fomblin HC products were tested in experimental animals for acute toxicity, primary and repeated insult irritancy, sensitization and photosensitization, subacute oral toxicity and comedogenicity; mutagenicity was examined in vitro, and irritancy or sensitization was also investigated on human skin (in patch tests with volunteers). A high molecular weight Fomblin HC only was tested in rats for subacute oral toxicity and in man for dermal effects. Single oral doses of 15 g/kg body weight were without evident toxicity to rats, as were single dermal applications or an ip injection at 5 g/kg. No primary irritant action was seen in rabbits or man, and similarly there was no evidence of skin sensitization or photosensitization in guinea pigs, or sensitization in man. No mutagenic action on Salmonella strains of tester bacteria was seen. In repeat dose irritancy or oral toxicity tests in rabbits or rats, no adverse effects of Fomblin HC products were noted; in particular, daily oral administration (1000 mg/kg/day) to rats over 28 days produced no significant reaction. No comedogenic action was found. From the known chemistry of the perfluoropolyethers, the test programme reported here and the limited published data, it is concluded that the intended use of Fomblin HC products in formulations applied to human skin has a high margin of safety.

  2. Characterization of the canine skin barrier restoration following acute disruption by tape stripping.

    PubMed

    Vidémont, Emilie; Mariani, Claire; Vidal, Stéphanie; Pin, Didier

    2012-04-01

    The stratum corneum (SC) forms the main part of the permeability barrier of the skin. In mice and in humans, cutaneous barrier disruption can be generated by removing the SC with tape stripping (TS) and the skin barrier function can be assessed by measurement of transepidermal water loss (TEWL). The aim of the present study was to characterize the skin barrier restoration in the dog following mechanical disruption and to analyse the correlation between the skin barrier recovery and TEWL measurement. Thirty sequential TS were performed on 12 sites on four healthy beagle dogs. The number of TS was chosen to ensure a sufficient barrier disruption with a slow recovery. Skin repair was assessed for 72 h by clinical and histological examinations, and TEWL measurements. The results showed that performing 30 TS was adequate to disrupt the skin barrier in the dog. The homeostatic repair response, initiated in the skin, was rapid and characterized by complete restoration of the SC within 72 h, accompanied by greater basal cell proliferation, and dermal eosinophilic inflammation. TEWL was significantly increased by complete removal of the SC but recovered along with restoration of the SC (Scheffe test, P ≤ 0.05). Characterization of a canine model of barrier disruption and restoration and assessment of the skin barrier function by TEWL measurements could help better understand the events implied in skin barrier function. Development of this canine model is also necessary for future studies on the effects of treatments aimed at restoring the skin barrier.

  3. Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions.

    PubMed

    Olivry, Thierry; Mayhew, David; Paps, Judy S; Linder, Keith E; Peredo, Carlos; Rajpal, Deepak; Hofland, Hans; Cote-Sierra, Javier

    2016-10-01

    Determining inflammation and itch pathway activation in patients with atopic dermatitis (AD) is fraught with the inability to precisely assess the age of skin lesions, thus affecting the analysis of time-dependent mediators. To characterize inflammatory events occurring during early experimental acute AD lesions, biopsy samples were collected 6, 24, and 48 hours after epicutaneous application of Dermatophagoides farinae house dust mites to sensitized atopic dogs. The skin transcriptome was assessed using a dog-specific microarray and quantitative PCR. Acute canine AD skin lesions had a significant up-regulation of genes encoding T helper (Th) 2 (e.g., IL4, IL5, IL13, IL31, and IL33), Th9 (IL9), and Th22 (IL22) cytokines as well as Th2-promoting chemokines such as CCL5 and CCL17. Proinflammatory (e.g., IL6, LTB, and IL18) cytokines were also up-regulated. Other known pruritogenic pathways were also activated: there was significant up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (TPS1) and mastin, neuromedin-B (NMB), nerve growth factor (NGF), and leukotriene-synthesis enzymes (ALOX5, ALOX5AP, and LTA4H). Experimental acute canine house dust mite-induced AD lesions exhibit an activation of innate and adaptive immune responses and pruritogenic pathways similar to those seen in humans with acute AD, thereby validating this model to test innovative therapeutics modalities for this disease. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Acute Dermal Irritation Study and Salmonella-Escherichia coli/Microsome Plate Incorporation Assay of Hydroprocessed Esters and Fatty Acids (HEFA) Bio-Based Jet Fuels

    DTIC Science & Technology

    2013-01-01

    microsome plate incorporation assay testing procedures were consistent with the OPPTS, Health Effects Test Guidelines, 870.5100 (U.S. EPA, 1998b). Both...exposure to the skin of NZW albino rabbits. This study is intended to provide information on the health hazards likely to arise from a short-term...be found in Appendix B. The purpose of this study was to provide data relating to the test substance’s health effects, environmental effects, or

  5. Irritants in cigarette smoke plumes

    SciTech Connect

    Ayer, H.E.; Yeager, D.W.

    1982-11-01

    Concentrations of the irritants formaldehyde and acrolein in side stream cigarette smoke plumes are up to three orders of magnitude above occupational limits, readily accounting for eye and nasal irritation. ''Low-tar'' cigarettes appear at least as irritating as other cigarettes. More than half the irritant is associated with the particulate phase of the smoke, permitting deposition throughout the entire respiratory tract and raising the issue of whether formaldehyde in smoke is associated with bronchial cancer.

  6. 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.

  7. Isolation and characterization of irritant components of Euphorbia pilulifera L.

    PubMed

    Saeed-ul-Hassan, Syed; Khalil-ur-Rehman, Muhammad; Niaz, Uzma; Saeed, Muhammad Asif; Hussain, Khalid; Rao, Saeed Ahmed; Ahmed, Irshad

    2013-01-01

    Euphorbia pilulifera is commonly found weed along road sides and loamy soils. This weed is commonly used as treatment of female disorders and respiratory problems. The latex of this weed causes irritation on hand on contact. To evaluate its irritant potentials, the dermatological investigation of irritant principles from locally occurring Euphorbia pilulifera was carried out. For this purpose, after collection and drying, a series of solvents with increasing polarity were used for the successive extraction of non-polar compounds (petroleum ether extract), constituents of intermediate polarities (chloroform extract) and polar constituents (methanol extract) from the whole herb of Euphorbia pilulifera. The chloroform extract of this weed was found most irritant to rabbit ' s skin. Chloroform extract was further subjected to column chromatography; four fractions Ep 1 to Ep 4 were isolated from active chloroform extract by column and thin layer chromatography. The irritant potentials of these isolated fractions were evaluated on rabbit 's skin. Two fractions out of the four, Ep 1 and Ep 3 appeared to be the most irritant than others. A possible structure activity relationship of these active compounds was discussed in order to establish their activity.

  8. Systematic review and network meta-analysis of tedizolid for the treatment of acute bacterial skin and skin structure infections caused by MRSA.

    PubMed

    McCool, Rachael; Gould, Ian M; Eales, Jacqui; Barata, Teresa; Arber, Mick; Fleetwood, Kelly; Glanville, Julie; Kauf, Teresa L

    2017-01-07

    Tedizolid, the active moiety of tedizolid phosphate, is approved in the United States, the European Union, Canada and a number of other countries for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This network meta-analysis (NMA) evaluates the comparative effectiveness of tedizolid and other antibacterials indicated for the treatment of ABSSSI caused by MRSA. Systematic review of 10 databases was undertaken to inform an NMA to estimate the relative effectiveness of tedizolid and established monotherapy comparators (ceftaroline, daptomycin, linezolid, teicoplanin, tigecycline, vancomycin) for treating MRSA-associated ABSSSI. Randomized controlled trials enrolling adults with ABSSSI or complicated skin and skin structure infections caused by suspected/documented MRSA were eligible for inclusion. Networks were developed based on similarity of study design, patient characteristics, outcome measures and available data. Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE) or test-of-cure assessment and treatment discontinuations resulting from adverse events (AEs). Bayesian NMA was conducted for each outcome using fixed-effects and random effects models. Literature searches identified 3,618 records; 15 trials met the inclusion criteria and were considered suitable for NMA comparison. In fixed-effects models, tedizolid had higher odds of clinical response at EOT (odds ratio [OR], 1.7; credible interval, 1.0, 3.0) and PTE than vancomycin (OR, 1.6; credible interval, 1.1, 2.5). No differences in odds of clinical response at EOT or PTE were observed between tedizolid and other comparators. There was no evidence of a difference among treatments for discontinuation due to AEs. Results from random effects and fixed-effects models were generally consistent. Tedizolid was superior to vancomycin for

  9. Nanolipidgel for enhanced skin deposition and improved antifungal activity.

    PubMed

    Wavikar, Preeti; Vavia, Pradeep

    2013-03-01

    The purpose of the research was to prepare and evaluate a topical nanolipidgel (NLH) of terbinafine hydrochloride (TRB), an antimycotic agent, for enhanced skin deposition and improved antifungal activity. Topical solid lipid nanoparticles (SLN) based nanolipidgel was formulated and evaluated. TRB-loaded SLNs were formulated by high-pressure homogenization technique. The stable TRB SLN dispersion was incorporated into a gel using 1% Carbopol 980 NF. Rheological evaluation and texture analysis of the TRB NLH was carried out. Skin permeation, skin deposition, antifungal activity, and occlusivity studies of the nanolipidgel formulation were carried out. The safety of the TRB NLH gel was evaluated using acute skin irritation test on New Zealand White rabbits. The SLN dispersion containing 10% of glyceryl monostearate, 3% of Tween 80, and 1% Plurol Oleique was the most stable. The optimized TRB SLN had a particle size and zeta potential value of 148.6±0.305 nm and -20.4±1.2 mV, respectively. TRB NLH had excellent rheological and texture properties to facilitate its topical application. TRB NLH showed increased skin deposition of the drug over plain (3-fold) and marketed TRB formulation (2-fold). TRB NLH had significantly enhanced antifungal activity against Candida albicans. TRB NLH showed efficient occlusivity and was non-irritant to the rabbit skin with no signs of erythema or edema. Solid lipid nanoparticles-based topical nanolipidgel of terbinafine can be an efficient, industrially scalable, and cost-effective alternative to the existing conventional formulations.

  10. Trait positive affect buffers the effects of acute stress on skin barrier recovery.

    PubMed

    Robles, Theodore F; Brooks, Kathryn P; Pressman, Sarah D

    2009-05-01

    This study examines the role of self-reported trait positive affect (PA) on skin barrier recovery after skin disruption, and whether the role of trait PA in wound healing is consistent with the direct effects model or the stress-buffering model of PA and health. Sixty healthy participants (mean age 22.7 +/- 3.9 years) completed a self-report measure of trait positive and negative affect, underwent a "tape-stripping" procedure that disrupts normal skin barrier function, and were randomly assigned to a Stress (Trier Social Stress Test) or No Stress (reading task) condition. Skin barrier recovery was assessed by measuring transepidermal water loss up to 2 hr after skin disruption. Multilevel modeling indicated that greater trait PA was related to faster skin barrier recovery (p < .05). The effects of PA on skin barrier recovery were independent of levels of trait NA. These findings suggest that trait PA may influence skin barrier recovery following a brief stressor. In addition, these results provide additional evidence that trait PA can positively impact objective health outcomes.

  11. Trait Positive Affect Buffers the Effects of Acute Stress on Skin Barrier Recovery

    PubMed Central

    Robles, Theodore F.; Brooks, Kathryn P.; Pressman, Sarah D.

    2010-01-01

    Objective This study examines the role of self-reported trait positive affect (PA) on skin barrier recovery after skin disruption, and whether the role of trait PA in wound healing is consistent with the direct effects model or the stress-buffering model of PA and health. Design Sixty healthy participants (mean age 22.7 ± 3.9 years) completed a self-report measure of trait positive and negative affect, underwent a “tape-stripping” procedure that disrupts normal skin barrier function, and were randomly assigned to a Stress (Trier Social Stress Test) or No Stress (reading task) condition. Main Outcome Measures Skin barrier recovery was assessed by measuring transepidermal water loss up to 2 hr after skin disruption. Results Multilevel modeling indicated that greater trait PA was related to faster skin barrier recovery (p < .05). The effects of PA on skin barrier recovery were independent of levels of trait NA. Conclusion These findings suggest that trait PA may influence skin barrier recovery following a brief stressor. In addition, these results provide additional evidence that trait PA can positively impact objective health outcomes. PMID:19450044

  12. Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

    PubMed Central

    Chin, Lee; Korpela, Elina; Kim, Anthony; Yohan, Darren; Niu, Carolyn; Wilson, Brian C.; Liu, Stanley K.

    2016-01-01

    Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting. PMID:27284926

  13. Skin protection in the prevention of skin diseases.

    PubMed

    Elsner, Peter

    2007-01-01

    Occupational skin diseases comprise a wide spectrum of conditions. Under epidemiological aspects, occupational contact dermatitis that is usually manifested on the hands is the most frequent occupational skin disease with an estimated average incidence rate of 0.7-1.5 cases per 1,000 workers per year. Irritant dermatitis is due to individual susceptibility and the exposure to irritants such as wet work combined with detergents or other hydrophilic irritants or solvents at the workplace. Chronic irritant dermatitis is a risk factor for delayed-type sensitization and subsequently allergic contact dermatitis. It is therefore the prevention of chronic or cumulative irritant dermatitis that is the decisive factor in the prevention of occupational skin disease. Within prevention programs at the workplace, skin protection plays an important, but limited role. Others are technical and organizational means to avoid or reduce skin exposure to irritants and allergens. Educational measures to increase the awareness of workers for workplace hazards and to motivate them to use skin protection measures appropriately are just as important as the careful selection of skin protection materials.

  14. Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections

    PubMed Central

    Jones, Travis M; Johnson, Steven W; DiMondi, V Paul; Wilson, Dustin T

    2016-01-01

    JNJ-Q2 is a novel, fifth-generation fluoroquinolone that has excellent in vitro and in vivo activity against a variety of Gram-positive and Gram-negative organisms. In vitro studies indicate that JNJ-Q2 has potent activity against pathogens responsible for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), such as Staphylococcus aureus and Streptococcus pneumoniae. JNJ-Q2 also has been shown to have a higher barrier to resistance compared to other agents in the class and it remains highly active against drug-resistant organisms, including methicillin-resistant S. aureus, ciprofloxacin-resistant methicillin-resistant S. aureus, and drug-resistant S. pneumoniae. In two Phase II studies, the efficacy of JNJ-Q2 was comparable to linezolid for ABSSSI and moxifloxacin for CABP. Furthermore, JNJ-Q2 was well tolerated, with adverse event rates similar to or less than other fluoroquinolones. With an expanded spectrum of activity and low potential for resistance, JNJ-Q2 shows promise as an effective treatment option for ABSSSI and CABP. Considering its early stage of development, the definitive role of JNJ-Q2 against these infections and its safety profile will be determined in future Phase III studies. PMID:27354817

  15. Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections.

    PubMed

    Sader, Helio S; Biedenbach, Douglas J; Paukner, Susanne; Ivezic-Schoenfeld, Zrinka; Jones, Ronald N

    2012-03-01

    BC-3781 is a novel semisynthetic pleuromutilin antimicrobial agent developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested by the broth microdilution method against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI. BC-3781 exhibited potent activity against methicillin-resistant Staphylococcus aureus (MIC(50/90), 0.12/0.25 μg/ml), coagulase-negative staphylococci (MIC(50/90), 0.06/0.12 μg/ml), β-hemolytic streptococci (MIC(50/90), 0.03/0.06 μg/ml), viridans group streptococci (MIC(50/90), 0.12/0.5 μg/ml), and Enterococcus faecium (including vancomycin-nonsusceptible strains) (MIC(50/90), 0.12/2 μg/ml). Compared with other antibiotics in use for the treatment of ABSSSI, BC-3781 displayed the lowest MICs and only a minimal potential for cross-resistance with other antimicrobial classes.

  16. Antimicrobial Activity of the Investigational Pleuromutilin Compound BC-3781 Tested against Gram-Positive Organisms Commonly Associated with Acute Bacterial Skin and Skin Structure Infections

    PubMed Central

    Biedenbach, Douglas J.; Paukner, Susanne; Ivezic-Schoenfeld, Zrinka; Jones, Ronald N.

    2012-01-01

    BC-3781 is a novel semisynthetic pleuromutilin antimicrobial agent developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested by the broth microdilution method against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI. BC-3781 exhibited potent activity against methicillin-resistant Staphylococcus aureus (MIC50/90, 0.12/0.25 μg/ml), coagulase-negative staphylococci (MIC50/90, 0.06/0.12 μg/ml), β-hemolytic streptococci (MIC50/90, 0.03/0.06 μg/ml), viridans group streptococci (MIC50/90, 0.12/0.5 μg/ml), and Enterococcus faecium (including vancomycin-nonsusceptible strains) (MIC50/90, 0.12/2 μg/ml). Compared with other antibiotics in use for the treatment of ABSSSI, BC-3781 displayed the lowest MICs and only a minimal potential for cross-resistance with other antimicrobial classes. PMID:22232289

  17. Medical Adhesive-Related Skin Injury Prevalence Among Adult Acute Care Patients: A Single-Center Observational Study.

    PubMed

    Farris, Marietta K; Petty, Michael; Hamilton, Jennifer; Walters, Shelley-Ann; Flynn, Michael A

    2015-01-01

    The purpose of this study was to measure the daily prevalence of adhesive product use and related skin injuries in adult patients in a non-intensive care unit setting. Prospective, descriptive study. The study sample consisted of patients cared for on 2 inpatient care units in a university-based acute care facility in the Midwestern United States. One was a 30-bed medical/surgical unit and the second was a 35-bed cardiac/telemetry unit. Their median age was 58 years; the average daily proportion of males and females was 56% and 42%, respectively. Medical adhesive-related skin injury (MARSI) prevalence was calculated using 3 methods: (1) the proportion of subjects who had any MARSI injury (subject prevalence), (2) the prevalence of MARSI by injury type and severity (severity prevalence), and (3) the proportion of medical adhesive products that had any associated MARSI (product prevalence). The daily subject prevalence of any MARSI injury ranged from 3.4% to 25.0% with a mean and median of 13.0% and 12.7%, respectively. The severity prevalence of MARSI injury ranged from 8 to 149 per 1000 product-days with a mean and median of 63 and 56 MARSIs per 1000 product-days, respectively. The median (range) product prevalence among all adhesive products varied from a high of 70 injuries per 1000 product-days for surgical closure to a low of 0 injuries per 1000 product-days for peripheral intravenous line dressing. Medical adhesive-related skin injury is a prevalent event in the acute care setting. Preventing skin injury has the potential to reduce complications, increase patient satisfaction, and improve clinical outcomes.

  18. Minimal Change Nephrotic Syndrome Sequentially Complicated by Acute Kidney Injury and Painful Skin Ulcers due to Calciphylaxis

    PubMed Central

    Sato, Ryuta; Akimoto, Tetsu; Imai, Toshimi; Nakagawa, Saki; Okada, Mari; Miki, Atsushi; Takeda, Shinichi; Yamamoto, Hisashi; Saito, Osamu; Muto, Shigeaki; Kusano, Eiji; Nagata, Daisuke

    2016-01-01

    Calciphylaxis is rare cutaneous manifestation associated with painful skin ulceration and necrosis. It primarily occurs in patients with end-stage chronic kidney disease. In this report, we would like to show our experience with a male patient presenting with minimal change nephrotic syndrome that was sequentially complicated by acute kidney injury and painful ulcerative cutaneous lesions due to calciphylaxis. There seemed to be several contributing factors, including a disturbance of the patient's mineral metabolism and the systemic use of glucocorticoids and warfarin. Various concerns regarding the diagnostic and therapeutic conundrums that were encountered in the present case are also discussed. PMID:27853075

  19. 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

  20. The developmental psychopathology of irritability.

    PubMed

    Leibenluft, Ellen; Stoddard, Joel

    2013-11-01

    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.

  1. Acute skin lesions following psoralen plus ultraviolet A radiation investigated by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liu, Z. M.; Zhong, H. Q.; Zhai, J.; Wang, C. X.; Xiong, H. L.; Guo, Z. Y.

    2013-08-01

    Psoralen plus ultraviolet A radiation (PUVA) therapy is a very important clinical treatment of skin diseases such as vitiligo and psoriasis, but associated with an increased risk of skin photodamage, especially photoaging. In this work, optical coherence tomography (OCT), a novel non-invasive imaging technology, was introduced to investigate in vivo the photodamage induced by PUVA qualitatively and quantitatively. Balb/c mouse dorsal skin was treated with 8-methoxypsoralen (8-MOP), and then exposed to UVA radiation. OCT images of the tissues were obtained by an OCT system with a 1310 nm central wavelength. Skin thickness and the attenuation coefficient were extracted from the OCT images to analyze the degree of injury to mouse skin. The results demonstrated that PUVA-treated skin showed an increase in skin thickness, and a reduction of attenuation coefficient in the OCT signal compared with the control groups. The data also showed good correlation with the results observed in histological sections using hematoxylin and eosin staining. In conclusion, OCT is a promising tool for photobiological studies aimed at assessing the effect of PUVA therapy in vivo.

  2. Clinical Response of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections by Severity Measure Using a Pooled Analysis From Two Phase 3 Double-Blind Trials.

    PubMed

    Sandison, Taylor; De Anda, Carisa; Fang, Edward; Das, Anita F; Prokocimer, Philippe

    2017-03-06

    Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). In a pooled analysis of 1,333 ABSSSI patients from the ESTABLISH clinical trials, treatment with tedizolid or linezolid demonstrated similar early and posttherapy clinical responses in both non-severe and severe disease, irrespective of the parameters used to measure ABSSSI severity. Shorter 6-day treatment of ABSSSI, including severe infections, with tedizolid phosphate demonstrated comparable efficacy to 10-day treatment with linezolid.

  3. Skin discolouration with acute onset parkinsonism secondary to systemic zirconium intoxication.

    PubMed

    Ryu, Hwa J; Yoon, Su J; Park, Jong-Tae; Kim, Young H; Jung, Jin M; Park, Moon-Ho; Rhyu, Im J; Kwon, Do-Young

    2014-01-01

    A 72-year-old woman presented with suspected parkinsonism and discolouration of the skin especially on sun-exposed areas. Thorough investigation revealed systemic zirconium intoxication due to intake of metallic colloids as a home remedy as a cause of the skin colour change. There may be an association between skin discolouration and her parkinsonism. This is unique in that various clinical manifestations developed following systemic ingestion of zirconium and this should serve as a warning on the risk of taking illicit dietary supplements.

  4. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

    PubMed

    Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

    2017-02-01

    Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

  5. [Irritable bowel syndrome].

    PubMed

    Kocián, J

    1994-04-01

    Irritable bowel is a functional gastrointestinal disorder with chronic or relapsing symptoms of abdominal pain and impaired frequency and consistency of the faeces caused by obscure structural or biochemical deviations. The frequency of the condition in civilized countries is estimated to amount to 15-20% of the population and it accounts for 25-50% of all patients in gastroenterological ambulatory departments. From the clinical aspect the type with dominant diarrhoea, typically in the morning and very compelling, and the type with pain and constipation are known but even combinations of the two types are encountered. A psychosomatic disorder of the motility of the large bowel and its tonus is involved associated with enhanced pain perception. Despite great efforts to find aetiopathogenetic factors, knowledge still is at the level of obscure theories. The diagnosis is still established per exclusion after all organic causes are ruled out, i.e. we always have to differentiate between an irritable bowel from an irritated one. In therapy the patient's confidence in his doctor is most important and it is essential to gain the patient's active cooperation. In case of diarrhoea a low-residue diet is used, calcium carbonate, codeine, loperamide, conversely in constipation adequate dietary fibre, intake metoclopramide or cisapride. Pain is relieved by spasmolytics or Ca channel blockers in the smooth musculature of the large bowel. The associated dysbiosis is transformed into eubiosis by Lactobacillus or other bacterial products.

  6. Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial.

    PubMed

    Buraczewska, I; Berne, B; Lindberg, M; Törmä, H; Lodén, M

    2007-03-01

    Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. Volunteers (n = 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of

  7. Skin tear prevention and management among patients in the acute aged care and rehabilitation units in the Australian Capital Territory: a best practice implementation project.

    PubMed

    Lopez, Violeta; Dunk, Ann Marie; Cubit, Katrina; Parke, Jill; Larkin, David; Trudinger, Maria; Stuart, Margaret

    2011-12-01

    A skin tear is a traumatic wound that results from the separation of the skin layers due to shearing forces, friction or blunt trauma that affects all people. Numerous preventative measures aim to reduce the skin tears and minimise conditions that predispose the epidermis to injury. With the increasing elderly population in acute aged care, implementation of an evidence-based guideline is critical as changes to ageing skin integrity make this population more susceptible to skin tear. The aim of this project was to ensure the practice of skin tear assessment, prevention and management among acute aged care causes and rehabilitation patients was performed according to best available evidence. This project utilised a pre- and post-implementation audit design using the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice programs. The project was conducted from June to November 2010 with the audits conducted in the acute aged care and rehabilitation units of two public hospitals in the Australian Capital Territory involving a sample size of 96 patients at pre-audit and 95 patient at post-audit admitted during the audit period. A convenience sample of 20 nurses also consented to be observed. The audits were conducted after obtaining ethics approval and consent from patients and nurses. The results showed a significant change in compliance to the skin tear guidelines at post-implementation audit. Staff education in particular had a dramatic increase from 20% to 98% and the point prevalence rate of hospital-acquired skin tear decreased from 10% to 0.15%. This project emphasised the importance of education of all personnel involved in patient care and that a simple assessment of skin integrity is critical in preventing and managing skin tear especially among the susceptible elderly population. 2011 The Authors. International Journal of Evidence-Based Healthcare. 2011 The Joanna Briggs Institute.

  8. Acute exacerbation of pain in irritable bowel syndrome: efficacy of phloroglucinol/trimethylphloroglucinol. A randomized, double-blind, placebo-controlled study

    PubMed Central

    Chassany, Olivier; Bonaz, B.; Bruley Des Varannes, S.; Bueno, L.; Cargill, Guillaume; Coffin, Benoit; Ducrotte, Philippe; Grange, V.

    2007-01-01

    Background Abdominal pain is the predominant symptom in IBS patients. Phloroglucinol (P) and its methylated derivative (TMP) are antispasmodic agents acting on smooth muscle. Aim To evaluate the efficacy of P/TMP on pain intensity during an acute exacerbation of pain of IBS over a one-week period treatment. Methods IBS Rome II patients seeking medical advice for an acute exacerbation of abdominal pain were randomised to P/TMP (62.2mg P + 80mg TMP) 2 pills tid or placebo for 7 days. Patients were included if they had a pain with a minimal intensity of 40 on a 100 mm visual analog scale, and if pain occurred at least 2 days during the week previous inclusion. Results 307 patients were included by 78 GPs. The intent to treat population included 300 patients, aged of 46.9±14.8 years (73% female). The relative decrease of pain intensity at day 7 was 57.8±31.7% vs. 46.3±34.7% (Δ=11.5±3.8%, [CI95%: 4.0; 19.1], p=0.0029) and the percentage of patients with at least a 50% decrease of pain intensity was 62.3% vs. 47.0% (Δ=15.3±5.7%, [CI95%: 4.1; 26.5], p=0.0078) in P/TMP and placebo groups respectively. Conclusions A one-week P/TMP treatment significantly reduces pain intensity in IBS patients consulting their GPs for pain exacerbation. PMID:17439513

  9. An observational study of personal ultraviolet dosimetry and acute diffuse reflectance skin changes at extreme altitude.

    PubMed

    Cheng, Ivy; Kiss, Alex; Lilge, Lothar

    2013-12-01

    To determine the level of UV radiation at extreme altitude and to assess the effect it has on the skin. Fifteen expeditioners and 10 Sherpas were assessed during a climbing expedition on the north side of Mt Everest (8848 m). UV exposure measurement and diffuse skin reflectance spectrophotometry were performed at the beginning and end of the expedition. Over the course of the expedition, the expeditioners and Sherpas received a median dose of 93.6 (interquartile range [IQR], 61.0-102.8) and 102.5 (IQR, 72.2-117.8) minimal erythemal doses (MEDs) of UV radiation. The maximum dosage exceeded 106 ± 1.4 MEDs. Using reflectance spectrophotometry, expeditioner and Sherpa melanin-hemoglobin increased by 83.6% (IQR, -1.5 to 89.8%) and 24.7% (IQR, -22.4 to 61.5%) for exposed skin, respectively. The amount of subcutaneous lipid-water decreased by a factor of 196.6 (IQR, 52.1-308.4) and 46.7 (IQR, 1.8-1156.5), for expeditioners and Sherpas, respectively. This expedition's participants received massive doses of UV radiation during their time at high altitude. In many individuals this was similar to the annual exposure of northern European office-workers (100 MEDs). Diffuse skin reflectance spectroscopy revealed considerable subcutaneous lipid loss, skin dehydration, and increased melanin in keeping with these levels of exposure. Copyright © 2013 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  10. A multicentre study of meticillin-resistant Staphylococcus aureus in acute bacterial skin and skin-structure infections in China: susceptibility to ceftaroline and molecular epidemiology.

    PubMed

    Zhang, Hui; Xiao, Meng; Kong, Fanrong; O'Sullivan, Matthew V N; Mao, Lei-Li; Zhao, Hao-Ran; Zhao, Ying; Wang, He; Xu, Ying-Chun

    2015-04-01

    Ceftaroline is a novel cephalosporin with activity against Gram-positive organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to investigate the susceptibility to ceftaroline of hospital-associated MRSA (HA-MRSA) isolates causing acute bacterial skin and skin-structure infections (ABSSSIs) in China and to examine their relationship by genotyping. A total of 251 HA-MRSA isolates causing ABSSSIs were collected from a multicentre study involving 56 hospitals in 38 large cities across 26 provinces in mainland China. All isolates were characterised by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, spa typing and detection of the Panton-Valentine leukocidin locus (lukS-PV and lukF-PV). Minimum inhibitory concentrations (MICs) of 14 antimicrobial agents, including ceftaroline, were determined by broth microdilution and were interpreted using Clinical and Laboratory Standards Institute breakpoints. The ceftaroline MIC50 and MIC90 values (MICs that inhibit 50% and 90% of the isolates, respectively) were 1 μg/mL and 2 μg/mL, respectively; 33.5% (n=84) of the isolates studied were ceftaroline-non-susceptible, with MICs of 2 μg/mL, but no isolate exhibited ceftaroline resistance (MIC>2 μg/mL). All of the ceftaroline-non-susceptible isolates belonged to the predominant HA-MRSA clones: 95.2% (n=80) from MLST clonal complex 8 (CC8), with the remaining 4.8% (n=4) from CC5. The high rate of non-susceptibility to ceftaroline amongst HA-MRSA causing ABSSSIs in China is concerning.

  11. Assessing the economic value of avoiding hospital admissions by shifting the management of gram+ acute bacterial skin and skin-structure infections to an outpatient care setting.

    PubMed

    Ektare, V; Khachatryan, A; Xue, M; Dunne, M; Johnson, K; Stephens, J

    2015-01-01

    To estimate, from a US payer perspective, the cost offsets of treating gram positive acute bacterial skin and skin-structure infections (ABSSSI) with varied hospital length of stay (LOS) followed by outpatient care, as well as the cost implications of avoiding hospital admission. Economic drivers of care were estimated using a literature-based economic model incorporating inpatient and outpatient components. The model incorporated equal efficacy, adverse events (AE), resource use, and costs from literature. Costs of once- and twice-daily outpatient infusions to achieve a 14-day treatment were analyzed. Sensitivity analyses were performed. Costs were adjusted to 2015 US$. Total non-drug medical cost for treatment of ABSSSI entirely in the outpatient setting to avoid hospital admission was the lowest among all scenarios and ranged from $4039-$4924. Total non-drug cost for ABSSSI treated in the inpatient setting ranged from $9813 (3 days LOS) to $18,014 (7 days LOS). Inpatient vs outpatient cost breakdown was: 3 days inpatient ($6657)/11 days outpatient ($3156-$3877); 7 days inpatient ($15,017)/7 days outpatient ($2495-$2997). Sensitivity analyses revealed a key outpatient cost driver to be peripherally inserted central catheter (PICC) costs (average per patient cost of $873 for placement and $205 for complications). Drug and indirect costs were excluded and resource use was not differentiated by ABSSSI type. It was assumed that successful ABSSSI treatment takes up to 14 days per the product labels, and that once-daily and twice-daily antibiotics have equal efficacy. Shifting ABSSSI care to outpatient settings may result in medical cost savings greater than 53%. Typical outpatient scenarios represent 14-37% of total medical cost, with PICC accounting for 28-43% of the outpatient burden. The value of new ABSSSI therapies will be driven by eliminating the need for PICC line, reducing length of stay and the ability to completely avoid a hospital stay.

  12. Phase II clinical study of BC-3781, a pleuromutilin antibiotic, in treatment of patients with acute bacterial skin and skin structure infections.

    PubMed

    Prince, W T; Ivezic-Schoenfeld, Z; Lell, C; Tack, K J; Novak, R; Obermayr, F; Talbot, G H

    2013-05-01

    This study investigated the potential of the novel systemic pleuromutilin antibiotic BC-3781 to treat patients with an acute bacterial skin and skin structure infection (ABSSSI) caused by a Gram-positive pathogen. Patients were randomized to intravenous BC-3781 100 mg, BC-3781 150 mg, or vancomycin 1 g every 12 h. Response to treatment was assessed daily and at test of cure (TOC). The primary endpoint was the clinical success rate at TOC in the modified intent-to-treat (MITT) and clinically evaluable (CE) analysis populations. Baseline characteristics, including the frequency of methicillin-resistant Staphylococcus aureus (MRSA), were comparable between the different treatment groups. Of 210 patients randomized, 186 (88.6%) patients completed the study. Clinical success at TOC in the CE population occurred in 54 (90.0%) patients in the BC-3781 100-mg group, 48 (88.9%) in the BC-3781 150-mg group, and 47 (92.2%) in the vancomycin group. At day 3, the clinical response rate was similar across the three treatment groups. Six patients discontinued study medication following an adverse event. The incidence rate for drug-related adverse events was lower for patients receiving BC-3781 (34.3% and 39.4% in the 100-mg and 150-mg groups, respectively) than those receiving vancomycin (53.0%). When BC-3781 was used to treat ABSSSIs caused by a Gram-positive pathogen, including MRSA, clinical success rates were comparable to those of the comparator, vancomycin. BC-3781 was generally well tolerated. These results provide the first proof of concept for the systemic use of a pleuromutilin antibiotic for the treatment of ABSSSIs.

  13. Phase II Clinical Study of BC-3781, a Pleuromutilin Antibiotic, in Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections

    PubMed Central

    Ivezic-Schoenfeld, Z.; Lell, C.; Tack, K. J.; Novak, R.; Obermayr, F.; Talbot, G. H.

    2013-01-01

    This study investigated the potential of the novel systemic pleuromutilin antibiotic BC-3781 to treat patients with an acute bacterial skin and skin structure infection (ABSSSI) caused by a Gram-positive pathogen. Patients were randomized to intravenous BC-3781 100 mg, BC-3781 150 mg, or vancomycin 1 g every 12 h. Response to treatment was assessed daily and at test of cure (TOC). The primary endpoint was the clinical success rate at TOC in the modified intent-to-treat (MITT) and clinically evaluable (CE) analysis populations. Baseline characteristics, including the frequency of methicillin-resistant Staphylococcus aureus (MRSA), were comparable between the different treatment groups. Of 210 patients randomized, 186 (88.6%) patients completed the study. Clinical success at TOC in the CE population occurred in 54 (90.0%) patients in the BC-3781 100-mg group, 48 (88.9%) in the BC-3781 150-mg group, and 47 (92.2%) in the vancomycin group. At day 3, the clinical response rate was similar across the three treatment groups. Six patients discontinued study medication following an adverse event. The incidence rate for drug-related adverse events was lower for patients receiving BC-3781 (34.3% and 39.4% in the 100-mg and 150-mg groups, respectively) than those receiving vancomycin (53.0%). When BC-3781 was used to treat ABSSSIs caused by a Gram-positive pathogen, including MRSA, clinical success rates were comparable to those of the comparator, vancomycin. BC-3781 was generally well tolerated. These results provide the first proof of concept for the systemic use of a pleuromutilin antibiotic for the treatment of ABSSSIs. PMID:23422913

  14. Use of Oritavancin in Acute Bacterial Skin and Skin Structure Infections Patients Receiving Intravenous Antibiotics: A US Hospital Budget Impact Analysis.

    PubMed

    Jensen, Ivar S; Lodise, Thomas P; Fan, Weihong; Wu, Chining; Cyr, Philip L; Nicolau, David P; DuFour, Scott; Sulham, Katherine A

    2016-02-01

    Nearly 10% of all US hospital admissions are attributed to acute bacterial skin and skin structure infections (ABSSSIs). While most antibacterials used to treat these infections require multi-day and multi-dose regimens, a single-dose treatment is now available. The objective of this analysis is to estimate the annual budget impact of using single-dose oritavancin in patients with moderate to severe ABSSSIs receiving intravenous methicillin-resistant Staphylococcus aureus (MRSA)-active antibacterials from a US hospital perspective. A decision-analytic model based on current clinical practice was developed to estimate the economic impact of oritavancin. Utilization of antibacterials and rates of hospital admission were derived from the Premier Research Database. Demographic and clinical data were informed by the published literature and 2014 wholesale drug acquisition costs were used. Other costs were based on the published literature and Medicare National Limitation amounts. All costs were inflated to 2014 US dollars. Two base-case scenarios were considered: one for hospitals with ambulatory services and one for hospitals without ambulatory services. For a US hospital with ambulatory services with 1000 ABSSSI patients receiving intravenous MRSA antibiotics annually, use of oritavancin in 26% of patients is estimated to reduce the total annual budget by 12.9% (US$1.23 million), or approximately US$1234.67 per patient. Total inpatient costs will be reduced by 22.3% (US$1.40 million) and outpatient costs will increase slightly by 1.7% (US$55,310). Pharmaceutical cost increases are offset by savings in the inpatient setting from fewer hospital admissions. Hospitals without ambulatory services are estimated to receive overall cost savings of 9.3% (US$0.63 million). Use of single-dose oritavancin in select ABSSSI patients with suspected or confirmed MRSA involvement is estimated to save US hospitals approximately 9.3-12.9% per year by reducing hospital admissions and

  15. 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

  16. Eye irritation hazard of chemicals and formulations assessed by methods in vitro.

    PubMed

    Jírová, Dagmar; Kejlová, Kristina; Janoušek, Stanislav; Bendová, Hana; Malý, Marek; Kolářová, Hana; Dvořáková, Markéta

    2014-01-01

    The aim of this study was to compare human and animal skin irritation data with results of selected in vitro methods, including HET-CAM test, Neutral Red Release Assay, Neutral Red Uptake Assay and EpiOcular eye irritation test and with already existing data of eye irritation obtained from animal experiments. Chemicals employed in previous skin irritation validation studies and commercially available cosmetic formulations were subjected to further testing using in vitro methods Neutral Red Release (NRR) assay, Neutral Red Uptake (NRU) assay, HET-CAM test and EpiOcular assay. The study revealed that skin irritants are not necessarily eye irritants; specifically volatile or solid materials may be misclassified. NRR assay provided false negative results in case of substances with fixative effect or not removable under standard washing procedure, emphasizing the role of microscopical evaluation as a crucial additional endpoint. Although overpredictive, HET-CAM test provided the lowest false negative rate. The most aggressive cosmetic formulation was correctly identified by EpiOcular assay, in accordance with NRU and NRR assays results, while HET-CAM test correctly identified the mildest formulation. Each of the in vitro methods is related to a specific endpoint of ocular irritation and provides only partial information on the mode of action of the tested material. Despite good reproducibility of individual in vitro assays, only the weight-of-evidence approach and results of multiple selected in vitro tests can allow for estimation of eye irritation hazard in vivo.

  17. Acute effects of cold therapy on knee skin surface temperature: gel pack versus ice bag

    PubMed Central

    Breslin, Matthew; Lam, Patrick; Murrell, George A C

    2015-01-01

    Background To our knowledge there has been no research that has compared the effectiveness of two popular cold therapy modalities applied to healthy human knees, with a surgical dressing, over a 4 h period. Hypothesis To determine whether gel packs are more effective than ice bags at reducing skin surface temperature in humans. Study design This was a randomised, repeated measures crossover study, which included nine healthy participants. Level of evidence Level 2. Methods Two cold therapy modalities—a gel pack (DonJoy-Orthopaedic Pty Ltd, Normanhurst, New South Wales, Australia) and an ice bag (ICE'N'EASY, Bokarina, Queensland, Australia)—were applied on top of a surgical dressing, covering the knee. Each participant randomly received two cold therapy treatments, in separate sessions, at least 4 days apart. Each session utilised the time protocol of 20 min application on the hour, for 4 h. Skin surface temperature was recorded throughout the session at 1 min intervals. Results In the first application, the ice bag (5°C±1.7°C) was more effective at reducing skin surface temperature (p<0.04) from baseline than the gel pack (4°C±0.9°C), and had a significantly greater cooling rate (p<0.02). On the subsequent three applications, both modalities were just as effective at reducing skin surface from baseline, and had similar cooling rates. Conclusions An ice bag initially was more effective than the gel pack at reducing skin surface temperature of healthy knees, with a surgical dressing. Over a 4 h period both gel packs and ice bags were just as effective at reducing skin surface temperature and at maintaining these lower temperatures. PMID:27900131

  18. Acute effects of cold therapy on knee skin surface temperature: gel pack versus ice bag.

    PubMed

    Breslin, Matthew; Lam, Patrick; Murrell, George A C

    2015-01-01

    To our knowledge there has been no research that has compared the effectiveness of two popular cold therapy modalities applied to healthy human knees, with a surgical dressing, over a 4 h period. To determine whether gel packs are more effective than ice bags at reducing skin surface temperature in humans. This was a randomised, repeated measures crossover study, which included nine healthy participants. Level 2. Two cold therapy modalities-a gel pack (DonJoy-Orthopaedic Pty Ltd, Normanhurst, New South Wales, Australia) and an ice bag (ICE'N'EASY, Bokarina, Queensland, Australia)-were applied on top of a surgical dressing, covering the knee. Each participant randomly received two cold therapy treatments, in separate sessions, at least 4 days apart. Each session utilised the time protocol of 20 min application on the hour, for 4 h. Skin surface temperature was recorded throughout the session at 1 min intervals. In the first application, the ice bag (5°C±1.7°C) was more effective at reducing skin surface temperature (p<0.04) from baseline than the gel pack (4°C±0.9°C), and had a significantly greater cooling rate (p<0.02). On the subsequent three applications, both modalities were just as effective at reducing skin surface from baseline, and had similar cooling rates. An ice bag initially was more effective than the gel pack at reducing skin surface temperature of healthy knees, with a surgical dressing. Over a 4 h period both gel packs and ice bags were just as effective at reducing skin surface temperature and at maintaining these lower temperatures.

  19. Examination of hospital length of stay in Canada among patients with acute bacterial skin and skin structure infection caused by methicillin-resistant Staphylococcus aureus

    PubMed Central

    Potashman, Michele H; Stokes, Michael; Liu, Jieruo; Lawrence, Robin; Harris, Linda

    2016-01-01

    Purpose Skin infections, particularly those caused by resistant pathogens, represent a clinical burden. Hospitalization associated with acute bacterial skin and skin structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to the economic burden of the disease. This study was conducted to provide current, real-world data on hospitalization patterns for patients with ABSSSI caused by MRSA across multiple geographic regions in Canada. Patients and methods This retrospective cohort study evaluated length of stay (LOS) for hospitalized patients with ABSSSI due to MRSA diagnosis across four Canadian geographic regions using the Discharge Abstract Database. Patients with ICD-10-CA diagnosis consistent with ABSSSI caused by MRSA between January 2008 and December 2014 were selected and assigned a primary or secondary diagnosis based on a prespecified ICD-10-CA code algorithm. Results Among 6,719 patients, 3,273 (48.7%) and 3,446 (51.3%) had a primary and secondary diagnosis, respectively. Among patients with a primary or secondary diagnosis, the cellulitis/erysipelas subtype was most common. The majority of patients presented with 0 or 1 comorbid condition; the most common comorbidity was diabetes. The mean LOS over the study period varied by geographic region and year; in 2014 (the most recent year analyzed), LOS ranged from 7.7 days in Ontario to 13.4 days in the Canadian Prairie for a primary diagnosis and from 18.2 days in Ontario to 25.2 days in Atlantic Canada for a secondary diagnosis. A secondary diagnosis was associated with higher rates of continuing care compared with a primary diagnosis (10.6%–24.2% vs 4.6%–12.1%). Conclusion This study demonstrated that the mean LOS associated with ABSSSI due to MRSA in Canada was minimally 7 days. Clinical management strategies, including medication management, which might facilitate hospital discharge, have the potential to reduce hospital LOS and related economic

  20. Acute toxicity of selected crude and refined shale oil derived and petroleum-derived substances

    SciTech Connect

    Smith, L.H.; Haschek, W.M.; Witschi, H.

    1980-01-01

    General information was obtained on the toxicity of selected samples of crude Paraho shale oil and some of its derivatives, some crude petroleums, and 3 refined petroleum products. Five tests were used to determine the acute toxicity of these substances: acute lethality in mice following oral or intraperitoneal administration of a single dose; acute dermal toxicity of a single dose in rats; delayed-type allergic contact hypersensitivity in guinea pigs; primary eye irritation and primary skin irritation of a single dose in rabbits. Histopathologic changes induced in mice following intraperitoneal injection of a single large dose of crude shale oil and two of its hydrotreated derivatives were examined. Studies also have been initiated to examine the tumor inducing potential of selected samples. The test system used was the mouse lung adenoma bioassay. The present report describes our findings and shows that all compounds tested have very low or no acute toxic effects in laboratory animals.

  1. Common industrial processes and occupational irritants and allergens--an update.

    PubMed

    Goh, C L

    1994-09-01

    This paper reviews the recent development of the industrial processes in the construction, electronics and metal industries which are the predominant industries in developing countries. Common occupational irritants and allergens are presented. The information is essential for occupational dermatologists and physicians managing patients with occupational skin diseases. In the construction industry, the prefabrication construction methods are now widely used. The commonest irritant is cement and the allergens are chromate, rubber chemicals and epoxy resins. In the electronics industry, the commonest irritants include soldering flux, solvent and fibreglass, and allergens include resins and metals, rubber chemicals and amines and colophony. Cutting fluid is the commonest occupational irritant in the metal industry. Biocides and metals in The electro-discharge machining process now widely used in the metal industry for precision engineering uses the electrodischarge machining fluids (EDM fluids) which are a strong skin irritant. Preventive measures including health education are most effective against occupational dermatitis.

  2. Effects of nanofiber/stem cell composite on wound healing in acute full-thickness skin wounds.

    PubMed

    Ma, Kun; Liao, Susan; He, Liumin; Lu, Jia; Ramakrishna, Seeram; Chan, Casey K

    2011-05-01

    Acute full-thickness skin wounds (FTSW) caused by extensive burns or high-energy trauma are not adequately addressed by current clinical treatments. This study hypothesized that biomimetic nanofiber scaffolds (NFSs) functionalized with rich attachment of bone-marrow-derived mesenchymal stem cells (BM-MSCs) can promote wound healing in acute FTSW. Results in a rat model showed that both NFS and BM-MSCs contributed to the wound healing. Wounds in NFS group with a higher density of BM-MSCs achieved complete closure 8 days earlier than the control group. Implanted BM-MSCs were found to promote epithelial edge ingrowth and collagen synthesis. The colocation of BM-MSCs (tagged with quantum-dots) with the expression of keratin 10 and filaggrin indicated the participation of BM-MSCs in epidermal differentiation at early and intermediate stages under the local wounding environment. Overall, this study suggests a great potential of using NFS/BM-MSC composites for the treatment of acute FTSW.

  3. Primary dermal and eye irritability tests of hydrophobically modified hydroxypropyl methylcellulose in rabbits.

    PubMed

    Obara, S; Muto, H; Kokubo, H; Ichikawa, N; Kawanabe, M; Tanaka, O

    1992-02-01

    Primary dermal and eye irritation tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether), a new cellulose derivative used as a thickener for topical pharmaceuticals and cosmetics, were conducted in rabbits. A dispersion of HM-HPMC (3%) was applied to intact and abraded skins and reactions were observed. A very slight erythema was observed in both skins and this polymer was categorized as a "mild irritant". In the eye irritation test, with a dispersion of the same concentration, it was categorized as "marginal" in unrinsed eyes and "negative" in rinsed eyes.

  4. A comparison of the irritant and allergenic properties of antiseptics.

    PubMed

    Lachapelle, Jean-Marie

    2014-01-01

    Over recent years, interest in the use of antiseptics has been reinforced as these molecules are not concerned by the problem of bacterial resistance. Whereas the in vitro efficacy of antiseptics has been well-studied, much less is known regarding their irritant and allergenic properties. This review provides an update on the comparative irritant and allergenic properties of commonly-used antiseptics in medicine nowadays. All antiseptics have irritant properties, especially when they are misused. Povidone-iodine has an excellent profile in terms of allergenicity. Allergic contact dermatitis is uncommon but is often misdiagnosed by practitioners, who confuse allergy and irritation. Chlorhexidine has been incriminated in some cases of allergic contact dermatitis; it is considered a relatively weak allergen, although it may rarely cause immunological contact urticaria and even life-threatening anaphylaxis. Octenidine is considered a safe and efficient antiseptic when used for superficial skin infections, however, aseptic tissue necrosis and chronic inflammation have been reported following irrigation of penetrating hand wounds. Polihexanide is an uncommon contact allergen as regards irritant and/or allergic contact dermatitis but cases of anaphylaxis have been reported. Considering the data available comparing the irritant and allergenic properties of major antiseptics currently in use, it should be acknowledged that all antiseptics may induce cutaneous side-effects. The present article reviews the most recent safety data that can guide consumers' choice.

  5. Study of surfactant-skin interactions by skin impedance measurements.

    PubMed

    Lu, Guojin; Moore, David J

    2012-02-01

    The stratum corneum (SC) plays a very critical physiological role as skin barrier in regulating water loss through the skin and protects the body from a wide range of physical and chemical exogenous insults. Surfactant-containing formulations can induce skin damage and irritation owing to surfactant absorption and penetration. It is generally accepted that reduction in skin barrier properties occurs only after surfactants have penetrated/permeated into the skin barrier. To mitigate the harshness of surfactant-based cleansing products, penetration/permeation of surfactants should be reduced. Skin impedance measurements have been taken in vitro on porcine skin using vertical Franz diffusion cells to investigate the impact of surfactants, temperature and pH on skin barrier integrity. These skin impedance results demonstrate excellent correlation with other published methods for assessing skin damage and irritation from different surfactant chemistry, concentration, pH, time of exposure and temperature. This study demonstrates that skin impedance can be utilized as a routine approach to screen surfactant-containing formulations for their propensity to compromise the skin barrier and hence likely lead to skin irritation.

  6. Eye irritation potential: palm-based methyl ester sulphonates.

    PubMed

    Yusof, Nor Zuliana; Azizul Hasan, Zafarizal Aldrin; Abd Maurad, Zulina; Idris, Zainab

    2017-07-31

    To evaluate eye irritation potential of palm-based methyl ester sulphonates (MES) of different chain lengths; C12, C14, C16, C16:18. The Bovine Corneal Opacity and Permeability test method (BCOP), OECD Test Guideline 437, was used as an initial step to study the inducing effect of palm-based MES on irreversible eye damage. The second assessment involved the use of reconstructed human corneal-like epithelium test method, OECD Test Guideline 492 using SkinEthic™ Human Corneal Epithelium to study the potential effect of palm-based MES on eye irritancy. The palm-based MES were prepared in 10% solution (w/v) in deionized water and tested as a liquid and surfactant test substances whereby both test conducted according to the liquid/surfactant treatment protocol. The preliminary BCOP results showed that palm-based MES; C12, C14, C16, C16:18 were not classified as severe eye irritants test substances with in vitro irritancy score between 3 and the threshold level of 55. The second evaluation using SkinEthic™ HCE model showed that palm-based MES; C12, C14, C16, C16:18 and three commercial samples were potentially irritants to the eyes with mean tissue viability ? 60% and classified as Category 2 according to United Nations Globally Harmonized System of Classification and Labelling of Chemicals. However, there are some limitations of the proposed ocular irritation classification of palm-based MES due to insolubility of long chain MES in 10% solution (w/v) in deionized water. Therefore, future studies to clarify the eye irritation potential of the palm-based MES will be needed, and could include; methods to improve the test substance solubility, use of test protocol for solids, and/or inclusion of a benchmark anionic surfactant, such as sodium dodecyl sulphate within the study design.

  7. The evolution of acute burn care - retiring the split skin graft.

    PubMed

    Greenwood, J E

    2017-07-01

    The skin graft was born in 1869 and since then, surgeons have been using split skin grafts for wound repair. Nevertheless, this asset fails the big burn patient, who deserves an elastic, mobile and robust outcome but who receives the poorest possible outcome based on donor site paucity. Negating the need for the skin graft requires an autologous composite cultured skin and a material capable of temporising the burn wound for four weeks until the composite is produced. A novel, biodegradable polyurethane chemistry has been used to create two such products. This paper describes the design, production, optimisation and evaluation of several iterations of these products. The evaluation has occurred in a variety of models, both in vitro and in vivo, employing Hunterian scientific principles, and embracing Hunter's love and appreciation of comparative anatomy. The process has culminated in significant human experience in complex wounds and extensive burn injury. Used serially, the products offer robust and elastic healing in deep burns of any size within 6 weeks of injury.

  8. 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

  9. Sensitive skin: mechanisms and diagnosis.

    PubMed

    Primavera, G; Berardesca, E

    2005-02-01

    Sensitive skin is a condition of subjective cutaneous hyperreactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sunscreens, and they often report worsening after exposure to dry and cold climate. Although no sign of irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present. Generally substances that are not commonly considered irritants are involved in this abnormal response. They include many ingredients of cosmetics such as: dimethyl sulfoxide, benzoyl peroxide preparations, salicylic acid, propylene glycol, amyldimethylaminobenzoic acid and 2-ethoxyethyl methoxycinnamate. Sensitive skin and subjective irritation are widespread but still far from being completely defined and understood. The aim of this paper is to summarize the relevant literature in order to elucidate the underlying mechanisms of sensitive skin and the best testing methodologies for investigation of sensitive skin.

  10. Evaluation of Eye Irritation Potential of Aqueous Leaf Extract of Achyranthes aspera by In Vitro and In Vivo Method.

    PubMed

    Rajpal Deshmukh, Gajanan; Hema Kumar, Kuntrapakam; Suresh Reddy, Poojari Venkata; Srinivasa Rao, Boddapati; Venkata Satish Kumar, Chirumamilla

    2012-01-01

    The present paper is an attempt to investigate the eye irritation potential of aqueous leaf extract of Achyranthes aspera by in vitro, Hen's Egg Chorioallantoic Membrane Test (HET-CAM) and in vivo acute eye irritation test in rabbits. The irritation score (IS) obtained after treatment of the extract on HET-CAM is 0.07 and that of in rabbits is 0.55, Which does not comes under either category 1 or 2 as per the harmonized integrated classification system. The aqueous extract of Achyranthes aspera showed no eye irritation properties both in vitro and in vivo methods when compared with negative control whereas positive controls showed eye irritation potential.

  11. TLD skin dose measurements and acute and late effects after lumpectomy and high-dose-rate brachytherapy only for early breast cancer

    SciTech Connect

    Perera, Francisco . E-mail: francisco.perera@lrcc.on.ca; Chisela, Frank; Stitt, Larry; Engel, Jay; Venkatesan, Varagur

    2005-08-01

    Purpose: This report examines the relationships between measured skin doses and the acute and late skin and soft tissue changes in a pilot study of lumpectomy and high-dose-rate brachytherapy only for breast cancer. Methods and Materials: Thirty-seven of 39 women enrolled in this pilot study of high-dose-rate brachytherapy (37.2 Gy in 10 fractions b.i.d.) each had thermoluminescent dosimetry (TLD) at 5 points on the skin of the breast overlying the implant volume. Skin changes at TLD dose points and fibrosis at the lumpectomy site were documented every 6 to 12 months posttreatment using a standardized physician-rated cosmesis questionnaire. The relationships between TLD dose and acute skin reaction, pigmentation, or telangiectasia at 5 years were analyzed using the GEE algorithm and the GENMOD procedure in the SAS statistical package. Fisher's exact test was used to determine whether there were any significant associations between acute skin reaction and late pigmentation or telangiectasia or between the volumes encompassed by various isodoses and fibrosis or fat necrosis. Results: The median TLD dose per fraction (185 dose points) multiplied by 10 was 9.2 Gy. In all 37 patients, acute skin reaction Grade 1 or higher was observed at 5.9% (6 of 102) of dose points receiving 10 Gy or less vs. 44.6% (37 of 83) of dose points receiving more than 10 Gy (p < 0.0001). In 25 patients at 60 months, 1.5% telangiectasia was seen at dose points receiving 10 Gy or less (1 of 69) vs. 18% (10 of 56) telangiectasia at dose points receiving more than 10 Gy (p 0.004). Grade 1 or more pigmentation developed at 1.5% (1 of 69) of dose points receiving less than 10 Gy vs. 25% (14 of 56) of dose points receiving more than 10 Gy (p < 0.001). A Grade 1 or more acute skin reaction was also significantly associated with development of Grade 1 or more pigmentation or telangiectasia at 60 months. This association was most significant for acute reaction and telangiectasia directly over the

  12. Acute leukemia after radiotherapy in a patient with Turcot's syndrome. Impaired colony formation in skin fibroblast cultures after irradiation

    SciTech Connect

    Li, F.P.; Little, J.B.; Bech-Hansen, N.T.; Paterson, M.C.; Arlett, C.; Garnick, M.B.; Mayer, R.J.

    1983-02-01

    Colonic polyposis and carcinoma developed in a woman with Turcot's syndrome at the age of 31 years; astrocytoma developed when she was 37. Her brother and sister had died of astrocytoma at the ages of 18 and 33 years, respectively. Progressive neutropenia developed in the patient three months after radiotherapy for her brain tumor and acute myelomonocytic leukemia 19 months after treatment. Three laboratories independently evaluated cultures of her skin fibroblasts for in vitro sensitivity to cell killing (loss of colony-forming ability) by x-rays. Survival assays consistently revealed slight but significant radiosensitivity in an early-passage (six to 10 doublings) fibroblast subculture. A later subculture (21 to 29 doublings) showed no abnormality, a possible effect of selective in vitro loss of radiosensitive cells.

  13. The Role of the Skin Barrier in Occupational Skin Diseases.

    PubMed

    Kasemsarn, Pranee; Bosco, Joanna; Nixon, Rosemary L

    2016-01-01

    Occupational skin diseases (OSDs) are the second most common occupational diseases worldwide. Occupational contact dermatitis (OCD) is the most frequent OSD, and comprises irritant contact dermatitis (ICD), allergic contact dermatitis (ACD), contact urticaria and protein contact dermatitis. There are many endogenous and exogenous factors which affect the development of OCD, including age, sex, ethnicity, atopic skin diathesis, certain occupations and environmental factors. One of the most important contributing causes is skin barrier dysfunction. The skin provides a first-line defense from environmental assaults and incorporates physical, chemical and biological protection. Skin barrier disturbance plays a crucial role in various skin diseases such as atopic dermatitis (AD), ichthyosis, ICD and ACD. Genetic factors, such as filaggrin gene (FLG) mutations, and external factors, such as skin irritants interfering with stratum corneum structure and composition, may lead to abnormalities in skin barrier function and increased vulnerability to skin diseases. FLG encodes the cornified envelope protein, filaggrin, which is involved in skin barrier function. FLG mutation is associated with the development of OCD. High-risk occupations for OCD include health care workers, hairdressers and construction workers. There are often multiple contributing causes to OCD, as workers are exposed to both irritants and allergens. AD is also associated with skin barrier disruption and plays an important role in OCD. ICD often precedes and facilitates the development of ACD, with impairment of the skin barrier contributing to the concurrence of ICD and ACD in many workers with OCD.

  14. Driver irritation and aggressive behaviour.

    PubMed

    Björklund, Gunilla M

    2008-05-01

    A sample of 98 drivers responded to a Swedish version of the UK Driving Anger Scale [UK DAS; [Lajunen, T., Parker, D., Stradling, S.G., 1998. Dimensions of driver anger, aggressive and highway code violations and their mediation by safety orientation in UK drivers. Transport. Res. Part F 1, 107-121]. The results indicated that the Swedish version, like the British original, measures three sources of driver irritation: "progress impeded", "reckless driving", and "direct hostility". Structural equation modelling was used to investigate the relationships between the three sources of self-reported driver irritation, aggressive actions, speed, sex, age, and annual mileage. The models suggested a positive relationship between the amount of driver irritation and frequency of aggressive actions for all three sources of irritation. Female drivers tended to become more irritated than male drivers, while the male drivers tended to act aggressively more often. Surprisingly, drivers who reported that they enjoy fast speeds did not become more irritated than slower drivers when obstructed. The important conclusions are that experienced irritation often leads to openly aggressively actions, and that expression of aggressive behaviours may be a cause of other drivers' feeling of irritation.

  15. Development of a cumulative irritation model for incontinence-associated dermatitis.

    PubMed

    Larner, J; Matar, H; Goldman, V S; Chilcott, R P

    2015-01-01

    Incontinence-associated dermatitis (IAD) is a painful yet preventable form of cumulative skin irritation prevalent amongst those with limited movement. Consequently, it has a significant impact on the quality of life for those affected as well as substantial cost implications. Prevention and intervention is typically through good skin hygiene regimes and regular use of barrier products. In this paper, we describe the development of an in vivo model of IAD in healthy volunteers by occluded application of alkaline synthetic urine to the volar aspect of volunteer's forearms for 6 h per day over a five-day period to reproduce the moist and irritant conditions causative of IAD. Irritation was assessed and quantified on a daily basis by a series of non-invasive biophysical measurements and compared to a contralateral saline-treated (control) site. Dermal irritation was assessed by subjective (visual) and objective measurements (laser Doppler and polarisation spectroscopic imaging, infrared thermography, skin reflectance spectroscopy, transepidermal water loss and skin surface pH). The provocation of reproducible, cumulative skin irritation was successfully demonstrated and quantified. This five-day model of irritation is considered appropriate for the initial clinical assessment of topical products to prevent or treat IAD.

  16. Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin.

    PubMed

    Holowatz, Lacy A; Thompson, Caitlin S; Kenney, W Larry

    2006-12-01

    Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated in older humans. NO may be decreased by an age-related increase in reactive oxygen species or a decrease in L-arginine availability via upregulated arginase. The purpose of this study was to determine the effect of acute antioxidant supplementation alone and combined with arginase inhibition on reflex VD in aged skin. Eleven young (Y; 22 +/- 1 yr) and 10 older (O; 68 +/- 1 yr) human subjects were instrumented with four intradermal microdialysis (MD) fibers. MD sites were control (Co), NO synthase inhibited (NOS-I), L-ascorbate supplemented (Asc), and Asc + arginase-inhibited (Asc + A-I). After baseline measurements, subjects underwent whole body heating to increase oral temperature (T(or)) by 0.8 degrees C. Red blood cell flux was measured by using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure) and normalized to maximal (CVC(max)). VD during heating was attenuated in O (Y: 37 +/- 3 vs. O: 28 +/- 3% CVC(max); P < 0.05). NOS-I decreased VD in both groups compared with Co (Y: 20 +/- 4; O: 15 +/- 2% CVC(max); P < 0.05 vs. Co within group). Asc and Asc + A-I increased VD beyond Co in O (Asc: 35 +/- 4% CVC(max); Asc + A-I: 41 +/- 3% CVC(max); P < 0.001) but not in Y (Asc: 36 +/- 3% CVC(max); Asc + A-I: 40 +/- 5% CVC(max); P > 0.05). Combined Asc + A-I resulted in a greater increase in VD than Asc alone in O (P = 0.001). Acute Asc supplementation increased reflex VD in aged skin. Asc combined with arginase inhibition resulted in a further increase in VD above Asc alone, effectively restoring CVC to the level of young subjects.

  17. Preoperative ultraviolet B inflammation in skin: Modelling individual differences in acute postoperative pain and neuro-immune interactions.

    PubMed

    Lunn, T H; Dawes, J M; Denk, F; Bennett, D L; Husted, H; Kehlet, H; McMahon, S B

    2017-09-14

    Neuroimmune interactions play a vital role in many of the most common pain conditions, such as arthritis. There have been many attempts to derive clinically predictive information from an individual's inflammatory response in order to gauge subsequent pain perception. Here, we wanted to test whether this effort could be enhanced and complemented by the use of a model system which takes into account the function of not just circulating, but also tissue-resident immune cells: ultraviolet B (UVB) irradiation of the skin. We conducted psychophysical and transcriptional analysis of hyperalgesia arising as a result of UVB-induced inflammation in patients before total knee arthroplasty (TKA, n = 23). Levels of acute postoperative pain were assessed and correlated with preoperative data. Cytokine and chemokine responses after UVB irradiation were found to be inversely correlated with the level of pain experienced after surgery (Spearman's ρ = -0.498). It may be possible to use this simple model to study and predict the nature of neuro-immune responses at more remote, clinically relevant sites. A simple model of UVB inflammation in the skin might predict the degree of a patient's neuro-immune response and the extent of their postoperative pain after total knee arthroplasty. © 2017 European Pain Federation - EFIC®.

  18. Expression of growth factor and receptor mRNAs in skin epithelial cells following acute cutaneous injury.

    PubMed Central

    Antoniades, H. N.; Galanopoulos, T.; Neville-Golden, J.; Kiritsy, C. P.; Lynch, S. E.

    1993-01-01

    We report that acute injury induces the expression of selective growth factor and growth factor receptors in the epithelial cells of the wounded tissue. In situ hybridization analysis of skin biopsy specimens obtained after cutaneous injury in swine demonstrated the induction of the expression of transforming growth factor-alpha, its receptor, epidermal growth factor-R, acidic fibroblast growth factor, and basic fibroblast growth factor messenger RNAs in the skin epithelial cells of the wounded tissue. There was no significant expression in the epithelial cells of control, uninjured tissues. The expression levels were maximal during the period of active tissue repair (1 to 5 days after injury) and were totally suppressed upon the healing of the wounded tissues. In contrast, insulinlike growth factor-I, (IGF-I), IGF-I receptor, and IGF-II receptor messenger RNAs were expressed in the epithelial cells of both the control, uninjured tissues and in tissue specimens obtained after injury. There was no significant expression of IGF-II messenger RNA in the epithelial cells before or after injury. It seems that injury induces the coordinated expression of selective growth factor and growth factor receptor genes whose products contribute to the regulation of the complex processes involved in tissue repair and remodeling. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8386442

  19. Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.

    PubMed

    Deck, Daniel H; Jordan, Jennifer M; Holland, Thomas L; Fan, Weihong; Wikler, Matthew A; Sulham, Katherine A; Ralph Corey, G

    2016-09-01

    Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. The Medicines Company

  20. In Vitro Activities of Tedizolid and Linezolid against Gram-Positive Cocci Associated with Acute Bacterial Skin and Skin Structure Infections and Pneumonia.

    PubMed

    Chen, Ko-Hung; Huang, Yu-Tsung; Liao, Chun-Hsing; Sheng, Wang-Hui; Hsueh, Po-Ren

    2015-10-01

    Tedizolid is a novel, expanded-spectrum oxazolidinone with potent activity against a wide range of Gram-positive pathogens. A total of 425 isolates of Gram-positive bacteria were obtained consecutively from patients with acute bacterial skin and skin structure infections (ABSSSIs) or pneumonia. These isolates included methicillin-susceptible Staphylococcus aureus (MSSA) (n = 100), methicillin-resistant Staphylococcus aureus (MRSA) (n = 100), Streptococcus pyogenes (n = 50), Streptococcus agalactiae (n = 50), Streptococcus anginosus group (n = 75), Enterococcus faecalis (n = 50), and vancomycin-resistant enterococci (VRE) (Enterococcus faecium) (n = 50). The MICs of tedizolid and linezolid were determined by the agar dilution method. Tedizolid exhibited better in vitro activities than linezolid against MSSA (MIC90s, 0.5 versus 2 μg/ml), MRSA (MIC90s, 0.5 versus 2 μg/ml), S. pyogenes (MIC90s, 0.5 versus 2 μg/ml), S. agalactiae (MIC90s, 0.5 versus 2 μg/ml), Streptococcus anginosus group (MIC90s, 0.5 versus 2 μg/ml), E. faecalis (MIC90s, 0.5 versus 2 μg/ml), and VRE (MIC90s, 0.5 versus 2 μg/ml). The tedizolid MICs against E. faecalis (n = 3) and VRE (n = 2) intermediate to linezolid (MICs, 4 μg/ml) were 1 μg/ml and 0.5 μg/ml, respectively. The tedizolid MIC90s against S. anginosus, S. constellatus, and S. intermedius were 0.5, 1, and 0.5 μg/ml, respectively, and the rates of susceptibility based on the U.S. FDA MIC interpretive breakpoints to the isolates were 16%, 28%, and 72%, respectively. Tedizolid exhibited 2- to 4-fold better in vitro activities than linezolid against a variety of Gram-positive cocci associated with ABSSSIs and pneumonia. The lower susceptibilities of tedizolid against isolates of S. anginosus and S. constellatus than against those of S. intermedius in Taiwan were noted. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Early inflammatory processes in the skin.

    PubMed

    Stamatas, G N; Morello, A P; Mays, D A

    2013-09-01

    Skin is considered as the border defining the limits of the body from the external world and functions as a barrier between the two. In this capacity, it has evolved to be an integral part of the innate and adaptive immune system. Although many reviews have described skin inflammation and processes that lead to its clinical manifestations, we are not aware of any reviews that have focused on immunologic activity occurring in the absence of any visual inflammatory cues. In this review, we discuss the importance of subclinical inflammation in human skin and its relevance to innate immune surveillance under physiologic conditions. Reactive oxygen species generated by metabolic processes, ultraviolet radiation or oxidizers may damage cells, initiating proinflammatory cascades. In addition to serving as structural skin components, keratinocytes have significant immunologic activity: they secrete proinflammatory cytokines and mediators, including interleukin (IL)-1α, IL-6, IL-10, tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor. Infant skin is particularly susceptible to irritation, inflammation and infection, since skin barrier function is not fully developed after birth and continues to mature throughout the first few years of life. Non-invasive methods such as fluorescence spectroscopy, spectral imaging and diffuse reflectance spectroscopy, as well as minimally invasive tape stripping, can be used to assess subclinical inflammatory markers in vivo, including erythema, epidermal cell proliferation rate and cytokine concentrations. Appropriately formulated skin care products may help maintain skin barrier integrity and enhance its capacity. In the future, assessment of subclinical inflammation may help clinicians prevent acute or chronic inflammatory conditions of the skin.

  2. Management of Central Venous Access Device-Associated Skin Impairment

    PubMed Central

    Broadhurst, Daphne; Moureau, Nancy

    2017-01-01

    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

  3. Definition and Facts for Irritable Bowel Syndrome

    MedlinePlus

    ... For Reporters Calendar of Events Follow Us Home Health Information Digestive Diseases Irritable Bowel Syndrome (IBS) Definition & Facts Related Topics Irritable Bowel Syndrome (IBS) Definition & ...

  4. [Bovine udder skin (BUS): testing of skin compatibility and skin protection].

    PubMed

    Pittermann, Wolfgang F; Kietzmann, Manfred

    2006-01-01

    New concepts of the horny layer as a metabolically active part of the epidermal permeability barrier elicited a re-evaluation of conventional mechanisms of occupational skin protection. Both skin protection products and noxae must penetrate the horny layer of the skin to be effective. The isolated perfused bovine udder skin (BUS) model reflects the natural penetration pattern; hence skin irritation, penetration and absorption can be investigated simultaneously. Using whole skin biopsies the degree of irritation in untreated (control), treated and pre-treated skin is measured by assessing the irritancy (PGE2-concentration) and cytotoxicity (MTT assay) after the exposure period of 0.5 h, 1.0 h and 5.0 h. Two types of skin protection studies were reported. One was a laboratory study using the water-soluble sodiumlaurylsulphate (10%, 15%) as noxa. The other study was initiated by a severely skin irritating water-soluble coolant (approx. 5%). This well documented case occurred in a metal working plant. In both studies different degrees of protective potential against the model noxae SLS and the coolant could be observed.

  5. Acute Dermal Toxicity of CHF1, CHR2 and Saline in Rabbits.

    DTIC Science & Technology

    1982-09-01

    irritation. This, in and of itself, is not unexpected. The soldier’s integumentary system is hardly immune to scratches and is frequently covered by soggy...animals and in vitro test systems . Severai of these materials have shown sufficent repellent activity and 0 persistence on the skin of animals to warrant...departments (1-3). A test for acute dermal toxicity evaluates the potential for systemic toxic effects of chemicals expected to come in contact with the

  6. [Irritable bowel syndrome].

    PubMed

    Truninger, K

    2007-04-01

    Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal disorders. The main symptoms are abdominal pain associated with a change in bowel habit. Headache and psychiatric disorders such as mood or anxiety disorders are often associated with IBS. Genetic predisposition, sensomotoric dysfunction, altered enteric inflammation and immune activation and disturbance of the brain-gut interaction are the most important pathogenetic factors. The diagnosis requires the new symptom-based Rome-III-criteria. Diagnostic testing primarily depends on the patients complaints, clinical and laboratory features and is then guided by the patient's age, symptom's severity and duration, alarm symptoms, psychosocial factors, and the family history for tumors. Treatment of IBS is based on an individualized evaluation and depends on disease severity, predominant symptoms and associated disorders. Treatment options include lifestyle modifications, drug therapy aimed at predominant symptoms and various forms of psychological treatments.

  7. A modified HET-CAM assay approach to the assessment of anti-irritant properties of plant extracts.

    PubMed

    Wilson, T D; Steck, W F

    2000-10-01

    Hen's egg--chorioallantoic membranes were used to screen for and assess anti-irritant properties among aqueous extracts of plants (HET-CAM tests), in connection with searches for plant-derived substances with topical anti-irritant action. The main question to be answered was whether CAM-assay screening of plant extracts could provide a useful route to identifying promising anti-irritant extracts for follow-up clinical testing. To be useful, the method would have to flag materials with strong anti-irritant properties, and would have to avoid registering false negatives. The tests conducted provided positive indications. We measured the delays in onset of three manifestations of membrane irritation-vascular hemorrhaging, membrane lysis and membrane coagulation-observed with test substances relative to positive controls. Aqueous 15% lactic acid, a commonly used irritant in direct tests on human skin, was employed as the test irritant in this study. The ratio [irritation onset times after test substance pre-treatment]:[onset times without test substance pretreatment] was used to measure the anti-irritant power of test substances. A scoring notation was devised for this which treats the delay parameters as independent effects. Most tested plant extracts showed no significant irritant or anti-irritant effects. Among the apparently anti-irritant plant extracts (approx. 10% of all those tested), most showed their greatest effect against hemorrhaging. Lesser but still readily measurable effects against membrane lysis and coagulation were also observed in nearly all the apparently anti-irritant extracts. Two of the tested extracts proved to be membrane irritants. Some key CAM assay results were compared with results obtained in direct tests on human skin using the same test irritant (15% lactic acid). In these comparative tests on skin, an essentially similar pattern of efficacy was obtained, with the plant extract deemed best in the CAM screenings, outperforming the

  8. Social Media under the Skin: Facebook Use after Acute Stress Impairs Cortisol Recovery.

    PubMed

    Rus, Holly M; Tiemensma, Jitske

    2017-01-01

    Social media's influence on stress remains largely unknown. Conflicting research suggests that Facebook use may both enhance and undermine psychosocial constructs related to well-being. Using novel experimental methods, this study examined the impact of social media use on stress recovery. Facebook users (n = 92, 49 males, mean age 19.55 SD = 1.63) were randomly assigned to use their own Facebook profile or quietly read after experiencing an acute social stressor. All participants showed significant changes in subjective and physiological stress markers during recovery. Participants who used Facebook experienced greater sustained cortisol concentration (p < 0.05) when controlling for gender and emotional investment in the website compared to controls. Results suggest that social media use may delay or impair recovery after experiencing an acute social stressor. This novel study incorporated objective physiological markers with subjective psychosocial measures to show that Facebook use may negatively impact well-being.

  9. Social Media under the Skin: Facebook Use after Acute Stress Impairs Cortisol Recovery

    PubMed Central

    Rus, Holly M.; Tiemensma, Jitske

    2017-01-01

    Social media's influence on stress remains largely unknown. Conflicting research suggests that Facebook use may both enhance and undermine psychosocial constructs related to well-being. Using novel experimental methods, this study examined the impact of social media use on stress recovery. Facebook users (n = 92, 49 males, mean age 19.55 SD = 1.63) were randomly assigned to use their own Facebook profile or quietly read after experiencing an acute social stressor. All participants showed significant changes in subjective and physiological stress markers during recovery. Participants who used Facebook experienced greater sustained cortisol concentration (p < 0.05) when controlling for gender and emotional investment in the website compared to controls. Results suggest that social media use may delay or impair recovery after experiencing an acute social stressor. This novel study incorporated objective physiological markers with subjective psychosocial measures to show that Facebook use may negatively impact well-being. PMID:28974938

  10. Skin capacitance imaging and corneosurfametry. A comparative assessment of the impact of surfactants on stratum corneum.

    PubMed

    Xhauflaire-Uhoda, Emmanuelle; Loussouarn, Geneviève; Haubrechts, Christelle; Léger, Didier Saint; Piérard, Gérald E

    2006-05-01

    Silicon image sensor (SIS) technology was recently introduced as an innovative tool (SkinChip, L'Oréal) providing sensitive imaging of the skin capacitance. This method can detect discrete focal variations in skin surface hydration, and thus early discrete manifestations of skin irritation induced by surfactants. In the present in vivo study, 2 neat and diluted shampoos, and 5% and 10% sodium laurylsulfate solutions were tested on human skin. Each surfactant solution was gently rubbed on the skin using wet hair wicks mimicking the casual use of a shampoo on the scalp. Clinical and SIS evaluations were carried out. In addition, the same products were tested using the ex vivo corneosurfametry bioassay performed on human stratum corneum (SC) harvested by cyanoacrylate skin surface strippings. The colourimetric index of mildness (CIM) was measured on these samples. The product reactivity with the SC was recognized by darker skin capacitance images, and by both lowered SkinChip-generated values and lowered CIM values. The extent in changes varied according to the nature of the test products and their concentrations. The SkinChip image changes likely corresponded to the acute surfactant-induced water swelling of the corneocytes. Skin capacitance imaging and corneosurfametry allow to disclose discrete surfactant-induced alterations of corneocytes.

  11. CAMP-reaction among skin isolates obtained from a dog with an acute squamous eczema.

    PubMed

    Brückler, J; Wibawan, I W; Lämmler, C

    1990-12-01

    The primary culture of a clinical specimen obtained from a dog with an acute squamous eczema revealed 3 different bacterial cultures. Two of these cultures, a beta-hemolytic Staphylococcus aureus and a group B streptococcal culture, demonstrated synergistic hemolytic activities on this primary culture plate. The group B streptococcus had the serotype surface antigens Ib/c, protein antigen c in its c beta component.

  12. Fluorescent light exposure incites acute and prolonged immune responses in zebrafish (Danio rerio) skin.

    PubMed

    Gonzalez, Trevor J; Lu, Yuan; Boswell, Mikki; Boswell, William; Medrano, Geraldo; Walter, Sean; Ellis, Samuel; Savage, Markita; Varga, Zoltan M; Lawrence, Christian; Sanders, George; Walter, Ronald B

    2017-09-29

    Artificial light produces an emission spectrum that is considerably different than the solar spectrum. Artificial light has been shown to affect various behavior and physiological processes in vertebrates. However, there exists a paucity of data regarding the molecular genetic effects of artificial light exposure. Previous studies showed that one of the commonly used fluorescent light source (FL; 4100K or "cool white") can affect signaling pathways related to maintenance of circadian rhythm, cell cycle progression, chromosome segregation, and DNA repair/recombination in the skin of male Xiphophorus maculatus. These observations raise questions concerning the kinetics of the FL induced gene expression response, and which biological functions become modulated at various times after light exposure. To address these questions, we exposed zebrafish to 4100K FL and utilized RNA-Seq to assess gene expression changes in skin at various times (1 to 12h) after FL exposure. We found 4100K FL incites a robust early (1-2h) transcriptional response, followed by a more protracted late response (i.e., 4-12h). The early transcriptional response involves genes associated with cell migration/infiltration and cell proliferation as part of an overall increase in immune function and inflammation. The protracted late transcriptional response occurs within gene sets predicted to maintain and perpetuate the inflammatory response, as well as suppression of lipid, xenobiotic, and melatonin metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions.

    PubMed

    Sîrbulescu, Ruxandra F; Boehm, Chloe K; Soon, Erin; Wilks, Moses Q; Ilieş, Iulian; Yuan, Hushan; Maxner, Ben; Chronos, Nicolas; Kaittanis, Charalambos; Normandin, Marc D; El Fakhri, Georges; Orgill, Dennis P; Sluder, Ann E; Poznansky, Mark C

    2017-09-18

    Chronic wounds affect 12-15% of patients with diabetes and are associated with a drastic decrease in their quality of life. Here we demonstrate that purified mature naïve B220(+) /CD19(+) /IgM(+) /IgD(+) B cells improve healing of acute and diabetic murine wounds after a single topical application. B cell treatment significantly accelerated acute wound closure by 2-3 days in wild-type mice and 5-6 days in obese diabetic mice. The treatment led to full closure in 43% of chronic diabetic wounds, as compared to only 5% in saline-treated controls. Applying equivalent numbers of T cells or disrupted B cells failed to reproduce these effects, indicating that live B cells mediated pro-healing responses. Topically-applied B cell treatment was associated with significantly reduced scar size, increased collagen deposition and maturation, enhanced angiogenesis and increased nerve growth into and under the healing wound. β-III tubulin+ nerve endings in scars of wounds treated acutely with B cells showed increased relative expression of growth-associated protein 43. The improved healing associated with B cell treatment was supported by significantly increased fibroblast proliferation and decreased apoptosis in the wound bed and edges, altered kinetics of neutrophil infiltration, as well as an increase in TGF-β and a significant reduction in MMP2 expression in wound granulation tissue. Our findings indicate that the timeline and efficacy of wound healing can be experimentally manipulated through the direct application of mature, naive B cells, which effectively modify the balance of mature immune cell populations within the wound microenvironment and accelerate the healing process. This article is protected by copyright. All rights reserved. © 2017 by the Wound Healing Society.

  14. Anti-irritative effect of methylrosaniline chloride (Gentian violet).

    PubMed

    Gloor, M; Wolnicki, D

    2001-01-01

    There are no published studies of the effect of methylrosaniline chloride (MRC) on inflammation when used at the concentration recommended in the New German Formulary. A tissue-damaging effect has been described in animal studies and at higher concentrations in humans. To determine whether 0.5% MRC increases or reduces skin damage in irritative dermatitis. The study was carried out on the sodium lauryl sulfate (SLS) skin irritation model in 18 healthy volunteers. The impact of intermittent treatment with 0.5% MRC or drug-free vehicle on three SLS exposure effects was determined: reduction of stratum corneum water content (corneometry), increase in subpapillary blood flow (laser Doppler method) and barrier damage (transepidermal water loss). MRC produced significant reductions in all three SLS exposure effects. Treatment of irritative dermatitis with 0.5% MRC is expected to produce a high clinical efficacy not only because of the compound's established antimicrobial activity, but also because of its anti-irritative effect. Copyright 2001 S. Karger AG, Basel

  15. Sensitive skin: an overview.

    PubMed

    Inamadar, Arun C; Palit, Aparna

    2013-01-01

    Sensitive skin is less tolerant to frequent and prolonged use of cosmetics and toiletries. It is self-diagnosed and typically unaccompanied by any obvious physical signs of irritation. With the change in lifestyle and also with increased opportunity to use many new brands of cosmetics and toiletries, there has been an increase in females complaining of unique sensation in their facial skin. Sensitive skin presents as smarting, burning, stinging, itching, and/or tight sensation in their facial skin. The condition is found in more than 50% of women and 40% of men, creating a sizable demand for products designed to minimize skin sensitivity. Good numbers of invasive and non-invasive tests are designed to evaluate and predict the sensitive skin. Management includes guidelines for selecting suitable cosmetics and toiletries in sensitive skin individuals.

  16. Dermoscopic Follow-Up of the Skin towards Acute Graft-versus-Host-Disease in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Kaminska-Winciorek, Grazyna; Czerw, Tomasz; Kruzel, Tomasz; Giebel, Sebastian

    2016-01-01

    Background. Acute graft-versus-host disease (aGVHD) involving skin is one of the most frequent complications of allogeneic hematopoietic stem cell transplantation (alloHSCT), usually diagnosed based on clinical manifestations. So far, skin biopsy with histopathological evaluation is the only method to confirm the diagnosis. Objective. In this prospective study we monitored alloHSCT recipients by dermoscopy in order to assess its utility as an alternative noninvasive tool to early diagnose acute GVHD. Methods. Thirteen consecutive patients who received alloHSCT were examined clinically and dermoscopically towards aGVHD [days 28 (±7), 56 (±7), and 100 (±7)], as well as in each patient who developed cutaneous aGVHD diagnosed according to clinical criteria (Glucksberg scale). Results. Six patients (46%) developed symptoms of cutaneous acute GVHD (grade 1, n = 3; grade 2, n = 3). Dermoscopic evaluation revealed pinkish or reddish background and well-visible, multiple thin telangiectasias. Conclusion. To our knowledge, this is the first report on the use of dermoscopy to evaluate skin involvement in the course of acute GVHD suggesting its role as a diagnostic tool in follow-up of GVHD, which can be also used before clinical symptoms occur. PMID:27446950

  17. Dermoscopic Follow-Up of the Skin towards Acute Graft-versus-Host-Disease in Patients after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Kaminska-Winciorek, Grazyna; Czerw, Tomasz; Kruzel, Tomasz; Giebel, Sebastian

    2016-01-01

    Background. Acute graft-versus-host disease (aGVHD) involving skin is one of the most frequent complications of allogeneic hematopoietic stem cell transplantation (alloHSCT), usually diagnosed based on clinical manifestations. So far, skin biopsy with histopathological evaluation is the only method to confirm the diagnosis. Objective. In this prospective study we monitored alloHSCT recipients by dermoscopy in order to assess its utility as an alternative noninvasive tool to early diagnose acute GVHD. Methods. Thirteen consecutive patients who received alloHSCT were examined clinically and dermoscopically towards aGVHD [days 28 (±7), 56 (±7), and 100 (±7)], as well as in each patient who developed cutaneous aGVHD diagnosed according to clinical criteria (Glucksberg scale). Results. Six patients (46%) developed symptoms of cutaneous acute GVHD (grade 1, n = 3; grade 2, n = 3). Dermoscopic evaluation revealed pinkish or reddish background and well-visible, multiple thin telangiectasias. Conclusion. To our knowledge, this is the first report on the use of dermoscopy to evaluate skin involvement in the course of acute GVHD suggesting its role as a diagnostic tool in follow-up of GVHD, which can be also used before clinical symptoms occur.

  18. Irritable bowel syndrome

    PubMed Central

    Enck, Paul; Aziz, Qasim; Barbara, Giovanni; Farmer, Adam D.; Fukudo, Shin; Mayer, Emeran A.; Niesler, Beate; Quigley, Eamonn M. M.; Rajilić-Stojanović, Mirjana; Schemann, Michael; Schwille-Kiuntke, Juliane; Simren, Magnus; Zipfel, Stephan; Spiller, Robin C.

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain–gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer. PMID:27159638

  19. A Complicated Course of Acute Viral Induced Pharyngitis, Icteric Hepatitis, Acalculous Cholecystitis, and Skin Rash

    PubMed Central

    Erfani, Seddigheh Sadat

    2016-01-01

    This case reveals the complexities and challenges in the diagnosis of acute Epstein-Barr virus (EBV) infection, indicating the potential relationship between EBV infection and severe icteric hepatitis, acalculous cholecystitis, and lymphocytic vasculitis. We suggest including EBV infectious mononucleosis in the list of differential diagnoses when any of these clinical syndromes (or a combination thereof) occurs without apparent cause, especially in the presence of lymphocytosis. To our knowledge, this is the first report to suggest the possible role of EBV in the pathogenesis of cutaneous lymphocytic vasculitis. Also it is possible that EBV infection triggered the flare-up of the underlying rheumatologic disease. Therefore, it could be assumed that a part of the clinical syndrome (e.g., dermatologic manifestations) might be related to the flare-up of the underlying rheumatologic disease. PMID:27847520

  20. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    PubMed

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements.

  1. Phenotypic characterization in situ of inflammatory cells in allergic and irritant contact dermatitis in man.

    PubMed Central

    Scheynius, A; Fischer, T; Forsum, U; Klareskog, L

    1984-01-01

    The cellular response in allergic and irritant contact dermatitis was analysed in situ with an immunohistochemical double staining technique. Allergic patch test reactions were elicited in 10 patients and irritant reactions in eight cases, using the Finn chamber technique. Skin biopsies were obtained 6-72 h after test applications. Frozen sections of 43 biopsies were investigated by simultaneous staining with rabbit anti-HLA-DR antibodies and various mouse monoclonal antibodies. The cell infiltrates were usually larger in the allergic than in the irritant reactions. However, the kinetics of the cell responses, the phenotypes of the inflammatory cells, their distribution and spatial relationships were similar. It thus appears that the applications of allergens or irritants to the skin generates a cell pattern that to a large extent reflects an immunological readiness for further immune reactions. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:6362938

  2. Molecular restrictions for human eye irritation by chemical vapors

    SciTech Connect

    Cometto-Muniz, J. Enrique . E-mail: ecometto@ucsd.edu; Cain, William S.; Abraham, Michael H.

    2005-09-15

    Previous research showed a cut-off along homologous volatile organic compounds (VOCs) in their ability to produce acute human mucosal irritation. The present study sought to specify the particular cut-off homolog for sensory eye irritation in an acetate and n-alcohol series. A 1900-ml glass vessel system and a three-alternative forced-choice procedure served to test nonyl, decyl, and dodecyl acetate, and 1-nonanol, 1-decanol, and 1-undecanol. Flowrate to the eye ranged from 2 to 8 L/min and time of exposure from 3 to 24 s. Decyl acetate and 1-undecanol were the shortest homologs that failed to produce eye irritation under all conditions, producing a cut-off effect. Increasing the vapor concentration of decyl acetate and 1-undecanol by 3 and 8 times, respectively, via heating them to 37 deg C made either or both VOCs detectable to only half of the 12 subjects tested, even though the higher vapor concentration was well above a predicted eye irritation threshold. When eye irritation thresholds for homologous acetates and n-alcohols were plotted as a function of the longest unfolded length of the molecule, the values for decyl acetate and 1-undecanol fell within a restricted range of 18 to 19 A. The outcome suggests that the basis for the cut-off is biological, that is, the molecule lacks a key size or structure to trigger transduction, rather than physical, that is, the vapor concentration is too low to precipitate detection.

  3. 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.

  4. Association of MHC region SNPs with irritant susceptibility in healthcare workers

    PubMed Central

    Yucesoy, Berran; Talzhanov, Yerkebulan; Barmada, M. Michael; Johnson, Victor J.; Kashon, Michael L.; Baron, Elma; Wilson, Nevin W.; Frye, Bonnie; Wang, Wei; Fluharty, Kara; Gharib, Rola; Meade, Jean; Germolec, Dori; Luster, Michael I.; Nedorost, Susan

    2017-01-01

    Irritant contact dermatitis is the most common work-related skin disease, especially affecting workers in “wet-work” occupations. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) and skin irritant response in a group of healthcare workers. 585 volunteer healthcare workers were genotyped for MHC SNPs and patch tested with three different irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH) and benzalkonium chloride (BKC). Genotyping was performed using Illumina Goldengate MHC panels. A number of SNPs within the MHC Class I (OR2B3, TRIM31, TRIM10, TRIM40 and IER3), Class II (HLA-DPA1, HLA-DPB1) and Class III (C2) genes were associated (p <0.001) with skin response to tested irritants in different genetic models. Linkage disequilibrium patterns and functional annotations identified two SNPs in the TRIM40 (rs1573298) and HLA-DPB1 (rs9277554) genes, with a potential impact on gene regulation. In addition, SNPs in PSMB9 (rs10046277 and ITPR3 (rs499384) were associated with hand dermatitis. The results are of interest as they demonstrate that genetic variations in inflammation-related genes within the MHC can influence chemical-induced skin irritation and may explain the connection between inflamed skin and propensity to subsequent allergic contact sensitization. PMID:27258892

  5. Irritable bowel syndrome.

    PubMed

    Spinelli, Antonella

    2007-01-01

    Irritable bowel syndrome (IBS) is a disease of unclear, complex pathophysiology characterised by abdominal pain and discomfort and altered bowel activity. It affects an estimated 10-15% of individuals worldwide and has a large impact on quality of life (QOL) and both direct and indirect healthcare costs. Symptoms of IBS are usually triggered by disruption of gastrointestinal (GI) function secondary to infection, dietary factors, lifestyle changes or psychological stress. While most currently available pharmacological treatments of IBS focus on symptomatic treatment of the syndrome, agents that attempt to address the pathophysiology of the disease, in particular the role of serotonin, have received much attention in recent years. However, there is growing concern that serotonergic agents as a class may be associated with rare, but serious, episodes of ischaemic colitis, with several cases of this complication having been reported in association with use of serotonergic agents that have reached the market. Thus, there remains an important need for safe and effective agents that treat the symptoms of IBS. Otilonium bromide, a spasmolytic agent, has been widely used worldwide and has been found to be effective and safe for managing abdominal pain. Clinical trials indicate that it improves baseline abdominal pain and distension, and is particularly effective in reducing diarrhoea. Combining otilonium bromide with benzodiazepines, such as diazepam, may improve the efficacy of the agent with respect to GI symptoms, while also treating underlying anxiety disorders. More research is required to confirm the efficacy and mechanisms of action associated with this combination therapy in IBS. Safety data from clinical trials and postmarketing sources indicate that otilonium bromide is well tolerated, with a safety profile comparable to placebo in clinical trials and only two reported cases of adverse reactions (urticaria) among 10-year postmarketing data. This article reviews

  6. Occupational skin diseases.

    PubMed

    Diepgen, Thomas L

    2012-05-01

    Occupational skin diseases are the most commonly reported notifiable occupational diseases. In Germany, 23 596 out of a total of 71 263 reported occupational diseases in 2010 were classified as occupational skin diseases (BK No. 5101: "severe or recurrent skin diseases which have forced the person to discontinue all occupational activities that caused or could cause the development, worsening, or recurrence of the disease"). Contact dermatitis (allergic, irritant) of the hands is the most common skin disease and atopic skin diathesis is often an important co-factor. The number of work-related skin diseases is many times higher than the number of notified occupational dermatoses. This CME article explains the legal framework of occupational diseases, the tasks and obligations of the legal statutory work insurance. Typical allergens and irritants of high risk professions are also presented as are the important steps from diagnosis to compensation. Early prevention of occupational skin diseases is very important to avoid severe chronic hand eczema. Therefore the "dermatologist's report" is crucial. Other occupational dermatoses (outside of BK 5101) are briefly mentioned. In recent years the number of notifications of occupational skin cancer due to occupational UV-irradiation has increased. According to recent epidemiological findings, there is a significant and consistent positive association between occupational UV-irradiation and squamous cell carcinoma. Therefore, an important criterion for a new occupational disease is fulfilled. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

  7. Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

    PubMed Central

    Jung, Karen; Sabri, Siham; Hanson, John; Xu, Yaoxian; Wang, Ying Wayne; Lai, Raymond; Abdulkarim, Bassam S

    2015-01-01

    Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their “M1/M2” activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased

  8. Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients.

    PubMed

    Jung, Karen; Sabri, Siham; Hanson, John; Xu, Yaoxian; Wang, Ying Wayne; Lai, Raymond; Abdulkarim, Bassam S

    2015-01-01

    Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their "M1/M2" activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 m

  9. Promotion of acute-phase skin wound healing by Pseudomonas aeruginosa C4 -HSL.

    PubMed

    Kanno, Emi; Kawakami, Kazuyoshi; Miyairi, Shinichi; Tanno, Hiromasa; Suzuki, Aiko; Kamimatsuno, Rina; Takagi, Naoyuki; Miyasaka, Tomomitsu; Ishii, Keiko; Gotoh, Naomasa; Maruyama, Ryoko; Tachi, Masahiro

    2016-12-01

    A Pseudomonas aeruginosa quorum-sensing system, which produces N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12 -HSL) and N-butanoyl-l-homoserine lactone (C4 -HSL), regulates the virulence factors. In our previous study, 3-oxo-C12 -HSL, encoded by lasI gene, was shown to promote wound healing. However, the effect of C4 -HSL, encoded by rhlI gene, remains to be elucidated. We addressed the effect of C4 -HSL on wounds in P. aeruginosa infection. Wounds were created on the backs of Sprague-Dawley SD rats, and P. aeruginosa PAO1 (PAO1) or its rhlI deletion mutant (ΔrhlI) or lasI deletion mutant (ΔlasI) was inoculated onto the wound. Rats were injected intraperitoneally with anti-C4 -HSL antiserum or treated with C4 -HSL at the wound surface. PAO1 inoculation led to significant acceleration of wound healing, which was associated with neutrophil infiltration and TNF-α synthesis. These responses were reversed, except for TNF-α production, when ΔrhlI was inoculated instead of PAO1 or when rats were co-treated with PAO1 and anti-C4 -HSL antiserum. In contrast, the healing process and neutrophil infiltration, but not TNF-α synthesis, were accelerated when C4 -HSL was administered in the absence of PAO1. This acceleration was not affected by anti-TNF-α antibody. These results suggest that C4 -HSL may be involved in the acceleration of acute wound healing in P. aeruginosa infection by modifying the neutrophilic inflammation. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  10. Acute toxicity and early cosmetic outcome in patients treated with multilumen balloon brachytherapy with skin spacing ≤ 7.0 millimeters

    PubMed Central

    Lee, Kiwhoon; Quillo, Amy; Dillon, Dustin; Sowards, Keith; Hatmaker, Allison

    2012-01-01

    Purpose To review institutional experience treating patients who underwent breast conserving surgery and adjuvant accelerated partial breast irradiation with multilumen balloon brachytherapy (MLB) with close skin spacing (≤7 mm). Material and methods Since July 2009, 26 patients with skin spacing ≤ 7.0 mm were treated with breast-conserving therapy and adjuvant MLB brachytherapy. Patients were treated with either the Contura or MammoSite ML catheter to a total dose of 34 Gy in 10 fractions. Patients were assessed for acute toxicity at the completion of treatment and 1-month post treatment. Cosmesis and late toxicity were assessed at three-month intervals thereafter. Results The median age of the patients was 56 years and median follow-up was 9 months. Sixteen patients had skin spacing of 5.0–7.0 mm, 10 with < 5.0 mm (median 5.8). The median percentage of the target (PTV_EVAL) receiving ≥ 95% of the prescription dose was 95.6%. The median volume of PTV_EVAL receiving ≥ 200% of the prescription dose was 6.1 cc. The maximum skin dose was 118.2% (median). The most commonly observed acute toxicity was grade 1-2 dermatitis (65.4%). The rate of post-treatment seroma and infection was 38.5% and 3.8%, respectively. Excellent/good cosmetic outcomes seen at the time of last follow-up was 92.3%. Conclusions MLB brachytherapy is safe and feasible in patients with close skin spacing, with acute toxicity and early cosmesis similar to other published series. These devices may broaden the application of balloon brachytherapy in patients previously excluded from this treatment based on anatomy. PMID:23346134

  11. Rat acute GvHD is Th1-driven and characterized by predominant donor CD4(+) T cell infiltration of skin and gut.

    PubMed

    Boieri, Margherita; Shah, Pranali; Jalapothu, Dasaradha; Zaitseva, Olena; Walter, Lutz; Rolstad, Bent; Naper, Christian; Dressel, Ralf; Inngjerdingen, Marit

    2017-02-23

    Acute graft-versus-host disease (aGvHD) remains a significant hurdle to successful treatment of many hematological disorders. The disease is caused by infiltration of allo-activated donor T cells primarily into the gastrointestinal tract and skin. While cytotoxic T cells mediate direct cellular damage, T helper (Th) cells differentially secrete immunoregulatory cytokines. Acute GvHD is thought to be primarily initiated by Th1 cells but a consensus is still lacking regarding the role of Th2 and Th17 cells. The aim of this study was to determine the contribution of distinct T cell subsets to aGvHD in the rat. Acute GvHD was induced by transplanting irradiated rats with T-cell depleted MHC-mismatched bone marrow, followed two weeks later by donor lymphocyte infusion. Near complete donor T cell chimerism was achieved in the blood and lymphatic tissues, in contrast to mixed chimerism in the skin and gut. Skin and gut donor T cells were predominantly CD4(+), in contrast to T cells in blood and lymphatic tissues. Genes associated with Th1 cells were up-regulated in gut, liver, lung, and skin tissues affected by aGvHD. Increased serum levels of CXCL10 and IL-18 preceded symptoms of aGvHD, accompanied by increased responsiveness to CXCL10 by blood CD4(+) T cells. No changes in expression of Th2- or Th17-associated genes were observed, indicating that aGvHD in this rat model is mainly Th1-driven. The rat model of aGvHD could be instrumental for further investigations of donor T cell subsets in the skin and gut, and for exploring therapeutic options to ameliorate symptoms of aGvHD.

  12. Severe Mucha-Habermann-Like Ulceronecrotic Skin Disease in T-Cell Acute Lymphoblastic Leukemia Responsive to Basiliximab and Stem Cell Transplant.

    PubMed

    Orenstein, Lauren A V; Coughlin, Carrie C; Flynn, Andrea T; Pillai, Vinodh; Boos, Markus D; Wertheim, Gerald B; Treat, James R; Teachey, David T

    2017-09-01

    A 5-year-old girl with T-cell acute lymphoblastic leukemia (T-ALL) developed a progressive eruption of crusted papules and ulcerative plaques involving 80% of her body surface area with histopathology consistent with febrile ulceronecrotic Mucha-Habermann disease (FUMHD), although multiple specimens also contained clonal leukemic cells. Her skin disease was refractory to many classic treatments for FUMHD, including methotrexate, and became so severe that concern about superinfection prevented intensification of chemotherapy for her malignancy. The addition of basiliximab promoted gradual improvement of the skin, allowing for chemotherapy intensification and subsequent bone marrow transplantation, after which the eruption resolved completely. This report describes a severe case of FUMHD-like eruption associated with clonal leukemic cells that improved with basiliximab, suggesting anti-CD25 therapy as a novel treatment for ulceronecrotic skin disease in the setting of high interleukin-2 levels. © 2017 Wiley Periodicals, Inc.

  13. Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus.

    PubMed

    Russi, Elvio G; Moretto, Francesco; Rampino, Monica; Benasso, Marco; Bacigalupo, Almalina; De Sanctis, Vitaliana; Numico, Gianmauro; Bossi, Paolo; Buglione, Michela; Lombardo, Antonino; Airoldi, Mario; Merlano, Marco C; Licitra, Lisa; Denaro, Nerina; Pergolizzi, Stefano; Pinto, Carmine; Bensadoun, Renè-Jean; Girolomoni, Giampiero; Langendijk, Johannes A

    2015-10-01

    The adverse effects of radiation therapy, often integrated with chemotherapy and/or targeted therapies, on the skin include severe acute and chronic dermatitis associated with pain, discomfort, itching, and burning, and may heavily affect patients' quality of life. The management of these skin adverse effects in head and neck cancer patients (HNCPs) are very heterogeneous due to the lack of shared rigorous classification systems and evidence based treatments. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of dermatitis in HNCPs treated with radiotherapy with or without systemic therapies in order to improve skin toxicity management. The Delphi Appropriateness Method was used. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. This paper offers contains seven clusters of statements about the management of dermatitis in HNCPs and a review of recent literature on these topics.

  14. 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

  15. Comparison of acute skin reaction following morning versus late afternoon radiotherapy in patients with breast cancer who have undergone curative surgical resection.

    PubMed

    Noh, Jae Myoung; Choi, Doo Ho; Park, Hyojung; Huh, Seung Jae; Park, Won; Seol, Seung Won; Jeong, Bae Kwon; Nam, Seok Jin; Lee, Jeong Eon; Kil, Won-Ho

    2014-05-01

    We investigated the relationship between the time of radiotherapy (RT) and treatment outcomes in breast cancer. Patients with pathologic T1-2N0-1 breast cancer who received adjuvant RT in the morning (before 10:00 AM) or late afternoon (after 3:00 PM) were eligible for inclusion in this study. We retrospectively compared the clinicopathologic characteristics, acute skin reaction, and survival outcomes according to the time of RT. The median follow-up duration was 83 months (range, 10-131 months). From the 395 eligible patients, 190 (48.1%) and 205 (51.9%) patients were classified into the morning RT group and the afternoon RT group, respectively. The clinicopathologic characteristics were relatively well balanced between the treatment groups, except for pathologic N-stage (P = 0.0409). Grade 2 or higher acute skin reaction according to the Radiation Therapy Oncology Group criteria was observed in 39 (9.9%) patients, with a higher frequency in the afternoon RT group than the morning RT group (13.7% vs 5.8%, respectively; P = 0.0088). There was no difference in the failure patterns or survival outcomes between the treatment groups. RT in late afternoon was associated with increased Grade 2 or more skin reaction after RT for breast cancer patients, but treatment outcomes did not differ according to the time of RT. Individualized considerations for treatment should be taken into account to reduce the risk of skin reactions.

  16. Acute skin toxicity-related, out-of-pocket expenses in patients with breast cancer treated with external beam radiotherapy: a descriptive, exploratory study.

    PubMed

    Schnur, Julie B; Graff Zivin, Joshua; Mattson, David M K; Green, Sheryl; Jandorf, Lina H; Wernicke, A Gabriella; Montgomery, Guy H

    2012-12-01

    Acute skin toxicity is one of the most common side effects of breast cancer radiotherapy. To date, no one has estimated the nonmedical out-of-pocket expenses associated with this side effect. The primary aim of the present descriptive, exploratory study was to assess the feasibility of a newly developed skin toxicity costs questionnaire. The secondary aims were to: (1) estimate nonmedical out-of-pocket costs, (2) examine the nature of the costs, (3) explore potential background predictors of costs, and (4) explore the relationship between patient-reported dermatologic quality of life and expenditures. A total of 50 patients (mean age = 54.88, Stage 0-III) undergoing external beam radiotherapy completed a demographics/medical history questionnaire as well as a seven-item Skin Toxicity Costs (STC) questionnaire and the Skindex-16 in week 5 of treatment. Mean skin toxicity costs were $131.64 (standard error [SE] = $23.68). Most frequently incurred expenditures were new undergarments and products to manage toxicity. Education was a significant unique predictor of spending, with more educated women spending more money. Greater functioning impairment was associated with greater costs. The STC proved to be a practical, brief measure which successfully indicated specific areas of patient expenditures and need. Results reveal the nonmedical, out-of-pocket costs associated with acute skin toxicity in the context of breast cancer radiotherapy. To our knowledge, this study is the first to quantify individual costs associated with this treatment side effect, as well as the first to present a scale specifically designed to assess such costs. In future research, the STC could be used as an outcome variable in skin toxicity prevention and control research, as a behavioral indicator of symptom burden, or as part of a needs assessment.

  17. Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide.

    PubMed

    Sugiura, Ayumi; Nomura, Tsuyoshi; Mizuno, Atsuko; Imokawa, Genji

    2014-07-01

    Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function and ceramide but not of beta-glucocerebrosidase activity. For the first time, we report an abnormal trans-epidermal water loss homeostasis in which delayed recovery kinetics of trans-epidermal water loss occurred on the first day during the 4 days after acute barrier disruption compared with healthy control skin. Interestingly, whereas the higher ceramide level in the stratum corneum of healthy control skin was further significantly up-regulated at 4 days post-tape stripping, the lower ceramide level in the stratum corneum of subjects with atopic dermatitis was not significantly changed. In a parallel study, whereas beta-glucocerebrosidase activity at 4 days post-tape stripping was significantly up-regulated in healthy control skin compared with before tape stripping, the level of that activity remained substantially unchanged in atopic dermatitis. These findings indicate that subjects with atopic dermatitis have a defect in sphingolipid-metabolic processing that generates ceramide in the interface between the stratum corneum and the epidermis. The results also support the notion that the continued disruption of barrier function in atopic dermatitis non-lesional skin is associated with the impaired homeostasis of a ceramide-generating process, which underscores an atopy-specific inflammation-triggered ceramide deficiency that is distinct from other types of dermatitis.

  18. In vitro evaluation of skin sensitivity of povidone-iodine and other antiseptics using a three-dimensional human skin model.

    PubMed

    Nagasawa, Mieko; Hayashi, Hiroyuki; Nakayoshi, Takemi

    2002-01-01

    Povidone-iodine (PVP-I) is an antiseptic which has been widely used in various fields. It was reported to have a weaker skin irritancy than other antiseptics in the Draize skin irritation test using rabbits. Recent increased concern for animal welfare requires us to use skin models in the tests as an alternative to animal testing. Actually, there are some skin models already commercialized, which are available to evaluate skin irritancy caused by e.g. chemical reagents, cosmetics or medicines. In this study, we evaluated the potential of a PVP-I solution and other antiseptics to cause irritation using a cultured human skin model (three-dimensional skin model) under conditions similar to clinical use. This skin model has two layers like a real skin, such as the dermis and epidermis which includes the cornified layer. For the evaluation of skin irritancy in this model, cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as an endpoint. Antiseptic formulations such as benzalkonium chloride (BAC), benzethonium chloride (BEC), chlorhexidine gluconate (CHG) and alkyldiaminoethylglycine hydrochloride (AEG) were used in this study. As a result, PVP-I showed a significantly weaker skin irritancy compared to the other antiseptics. The present in vitro study results revealed a correlation with the results of previously conducted in vivo skin irritancy tests using rabbits. Copyright 2002 S. Karger AG, Basel

  19. Assessment of dermal safety of Scutellaria baicalensis aqueous extract topical application on skin hypersensitivity.

    PubMed

    Kim, Tae-Won; Song, In-Bae; Lee, Hong-Ki; Kim, Myoung-Seok; Ham, Seoung-Ho; Cho, Jung-Hee; Lim, Jong-Hwan; Yun, Hyo-In

    2013-07-01

    Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the β-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhler's method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. β-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.

  20. The skin compatibility of distilled tall oils: evaluation with the bovine udder skin in vitro model system.

    PubMed

    Pittermann, Wolfgang; Hopfgarten, Fredrik; Kietzmann, Manfred

    2009-02-01

    Distilled tall oil (DTO) is a natural product, often added as an emulsifying ingredient in cutting fluids used as lubricants and coolants in metal working. The in vitro model used to test the skin compatibility of these substances, was the isolated perfused ex vivo bovine udder skin (BUS) model. After three exposure periods (0.5, 1, and 5 hours), cytotoxic effects were determined by using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and tissue levels of the pre-inflammatory mediator prostaglandin E2 (PGE2) in treated whole skin biopsies were assessed by using an enzyme immunoassay. The BUS standard study design, involving a single application, was previously developed to investigate the skin irritation potential of cosmetics and chemicals. In the current study, four different batches of undiluted DTO, and tall oil fatty acids as a reference compound, were applied both singly and repeatedly (three times), under open conditions which were in line with the potential usage conditions in the work place. Under the standardised single application conditions, no major differences in cytotoxic effects or PGE2 levels between the samples were apparent, so no indication of a skin irritation potential could be concluded. This result is in accordance with prior in vivo studies for acute dermal toxicity. Under repeated application conditions, signs of cytotoxicity were observed after the application of one of the DTO samples, which was known to be derived from different raw materials. Therefore, it was concluded that, generally, the presence of DTO at a concentration of up to 10% in cutting fluids, is not expected to result in any DTO-related deterioration of the skin.

  1. An objective long-term evaluation of Integra (a dermal skin substitute) and split thickness skin grafts, in acute burns and reconstructive surgery.

    PubMed

    Nguyen, Dai Q A; Potokar, Tom S; Price, Patricia

    2010-02-01

    The field of wound healing and tissue repair has advanced rapidly in the last decade, with this there is an increasing emphasis on the importance of the functional and cosmetic outcomes following injury. Integra artificial skin is the most widely used synthetic skin substitute and is reported to have better outcomes in relation to the appearance and elasticity when compared to split thickness skin grafting (SSG). A review of the literature reveals very few trials that are based on an objective evaluation of Integra treated scars as compared to SSGs. This research aimed to provide objective data on the long-term outcome of Integra. All adult patients from the Welsh Burns Centre who had been successfully treated with Integra+/-SSG were invited to attend a clinic for a follow up provided they had been healed for greater than one year. The hypothesis that Integra scars are more pliable than skin grafts was tested objectively using the Cutometer, a suction device which measures skin elasticity. Of the 13 patients eligible, six were available for assessment. The results of this study suggest that Integra treated sites correlate well with normal skin as measured by the Cutometer. This was statistically significant for the parameters Ur/Ue (elastic function) and Ur/Uf (gross elasticity). On the other hand there was no correlation seen between the patients SSG sites and the patient's normal skin. With advances in medicine we are increasingly able to modulate wound healing and the resultant scars. In order to assess new and often costly treatments the need for objective scar measurement tools have become apparent. Integra has been advocated to improve scarring from injury. However, there have been few studies to evaluate the long-term outcome of Integra as compared to traditional methods such as SSG. In the past scar evaluation has been based on subjective scores by patients and clinicians. Now the mechanical properties of the skin can be evaluated using simple

  2. Quetiapine reduces irritability and risk of suicide in patients with agitated depression.

    PubMed

    Nishiyama, Akiyoshi; Matsumoto, Hideo

    2013-07-20

    Patients who suffer from agitated depression accompanied by psychomotor agitation and irritability are prone to suicidal ideation and attempts and must therefore be diagnosed and treated with utmost care. Clinically, there have been more than a few cases of suicidal attempts that seemed to have been provoked by careless prescription of antidepressant medication. In the present study, administration of quetiapine to 3 patients in the acute phase of agitated depression resulted in rapid improvement in irritability and alleviation of depression. Depression in these 3 patients was caused by chronic (persistent) anxiety and tension. During the acute phase, the patients evidenced psychomotor agitation and irritability, often experiencing a sudden, overwhelming urge to commit suicide. Findings from the present study suggest that treatment with quetiapine in patients with this type of agitated depression can quickly alleviate symptoms of anxiety and irritability and reduce the risk of suicide.

  3. Prevalence of Acute Symptoms among Workers in Printing Factories

    PubMed Central

    Decharat, Somsiri

    2014-01-01

    Objective. To identify socioeconomic situation factors and behavioral factors associated with the prevalence of acute symptoms among 150 printing workers in 16 printing factories in Southern Thailand. Materials and Methods. A cross-sectional study was conducted by interviewing 150 printing workers in 16 printing factories in Southern Thailand. Results. Acute symptoms comprised dizziness, drowsiness, eye irritation, light-headedness, rhinitis, shortness of breath, cough, chest tightness, nausea/vomiting, exacerbation of asthma, allergic skin reaction, and visual disorder. The prevalence of symptoms was consistently higher among workers in the printing process than among other workers. Smoking cigarettes and drinking alcohol were not associated with an increased prevalence of acute symptoms among these printing-factory workers. Conclusion. The significant associations were found between personal protective equipment and personal hygiene and prevalence of acute symptoms in printing workers. PMID:25386365

  4. Radiation-induced stress response in peripheral blood of breast cancer patients differs between patients with severe acute skin reactions and patients with no side effects to radiotherapy.

    PubMed

    Skiöld, Sara; Naslund, Ingemar; Brehwens, Karl; Andersson, Arja; Wersall, Peter; Lidbrink, Elisabet; Harms-Ringdahl, Mats; Wojcik, Andrzej; Haghdoost, Siamak

    2013-08-30

    The aim of the study was to compare the radiation-induced oxidative stress response in blood samples from breast cancer patients that developed severe acute skin reactions during the radiotherapy, with the response in blood samples from patients with no side effects. Peripheral blood was collected from 12 breast cancer patients showing no early skin reactions after radiotherapy (RTOG grade 0) and from 14 breast cancer patients who developed acute severe skin reactions (RTOG grade 3-4). Whole blood was irradiated with 0, 5 and 2000mGy γ-radiation and serum was isolated. The biomarker for oxidative stress, 8-oxo-dG, was analyzed in the serum by a modified ELISA. While a significant radiation-induced increase of serum 8-oxo-dG levels was observed in serum of the RTOG 0 patients, no increase was seen in serum of the RTOG 3-4 patients. The radiation induced increase in serum 8-oxo-dG levels after 5mGy did not differ significantly from the increase observed for 2000mGy in the RTOG 3-4 cohort, thus no dose response relation was observed. A receiver operating characteristic (ROC) value of 0.97 was obtained from the radiation-induced increase in 8-oxo-dG indicating that the assay could be used to identify patients with severe acute adverse reactions to radiotherapy. The results show that samples of whole blood from patients, classified as highly radiosensitive (RTOG 3-4) based on their skin reactions to radiotherapy, differ significantly in their oxidative stress response to ionizing radiation compared to samples of whole blood from patients with no skin reactions (RTOG 0). Extracellular 8-oxo-dG is primarily a biomarker of nucleotide damage and the results indicate that the patients with severe acute skin reactions differ in their cellular response to ionizing radiation at the level of induction of oxidative stress or at the level of repair or both. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Relative biological effectiveness of carbon ions for tumor control, acute skin damage and late radiation-induced fibrosis in a mouse model.

    PubMed

    Sørensen, Brita S; Horsman, Michael R; Alsner, Jan; Overgaard, Jens; Durante, Marco; Scholz, Michael; Friedrich, Thomas; Bassler, Niels

    2015-01-01

    The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of the right hind limb were irradiated with single fractions of either photons, or (12)C ions using a 30-mm spread-out Bragg peak. The endpoint of the study was local control (no tumor recurrence within 90 days). For the acute skin reaction, non-tumor bearing CDF1 mice were irradiated with a comparable radiation scheme, and monitored for acute skin damage between Day 7 and 40. Late RIF was assessed in the irradiated mice. The TCD50 (dose producing tumor control in 50% of mice) values with 95% confidence interval were 29.7 (25.4-34.8) Gy for C ions and 43.9 (39.2-49.2) Gy for photons, with a corresponding Relative biological effectiveness (RBE) value of 1.48 (1.28-1.72). For acute skin damage the MDD50 (dose to produce moist desquamation in 50% of mice) values with 95% confidence interval were 26.3 (23.0-30.1) Gy for C ions and 35.8 (32.9-39.0) Gy for photons, resulting in a RBE of 1.36 (1.20-1.54). For late radiation-induced fibrosis the FD50 (dose to produce severe fibrosis in 50% of mice) values with 95% confidence interval were 26.5 (23.1-30.3) Gy for carbon ions and 39.8 (37.8-41.8) Gy for photons, with a RBE of 1.50 (1.33-1.69). The observed RBE values were very similar for tumor response, acute skin damage and late RIF when irradiated with large doses of high- linear energy transfer (LET) carbon ions. This study adds information to the variation in biological effectiveness in different tumor and normal tissue models.

  6. Unexpected skin barrier influence from nonionic emulsifiers.

    PubMed

    Bárány, E; Lindberg, M; Lodén, M

    2000-02-15

    Skin disorders are often treated with creams containing various active substances. The creams also contain emulsifiers, which are surface-active ingredients used to stabilize the emulsion. Emulsifiers are potential irritants and in the present study the influence of stearic acid, glyceryl stearate, PEG-2, -9, -40, and -100 stearate, steareth-2, -10 and -21 on normal as well as on irritated skin have been evaluated with non-invasive measurements. Test emulsions were created by incorporating 5% emulsifiers in a water/mineral oil mixture (50:50). The emulsions and their vehicle were then applied to normal skin for 48 h and to sodium lauryl sulfate (SLS) damaged skin for 17 h in aluminum chambers. Twenty-four hours after removal of the chambers the test sites were evaluated for degree of irritation. In normal skin, the emulsifiers induced significant differences in TEWL but not in skin blood flow. Five of the emulsifiers increased TEWL. In SLS-damaged skin an aggravation of the irritation was expected. However, no differences regarding skin blood flow was noted from the emulsifiers. Furthermore, three emulsifiers unexpectedly decreased TEWL. These results highlight the possibility of absorption of these emulsifiers into the lipid bilayer, which increase TEWL in normal skin and decrease TEWL in damaged skin.

  7. Effects of olive leaf extract and its main component oleuroepin on acute ultraviolet B irradiation-induced skin changes in C57BL/6J mice.

    PubMed

    Sumiyoshi, Maho; Kimura, Yoshiyuki

    2010-07-01

    Olive (Olea europaea L.) leaves have long been used in folk medicine and herbal tea in Europe and the Mediterranean area. The Mediterranean climate is characterized by high temperatures, and by strong ultraviolet B (UVB) radiation causing the skin to age, increasing wrinkling, pigmentation and skin thickness. The aim of this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage caused by acute UVB irradiation in C57BL/6J mice. The extract (300 or 1000 mg/kg) and oleuropein (25 or 85 mg/kg) were administered orally twice daily for 14 days. UVB was administered daily at a dose of 120 mJ/cm(2) for the first 5 days and then every other day for 9 days. Both treatments inhibited the increases in skin thickness induced by radiation. They also inhibited increases in the Ki-67- and 8-hydroxy-2'-deoxyguanosine-positive cell numbers, melanin granule area and matrix metalloproteinase-13 (MMP-13) expression. These preventive effects on UVB-induced skin damage might be caused in part by inhibiting the degradation of extracellular matrixes in the corium, and by the proliferation of epidermal cells through the inhibition of increases in MMP-13 levels and reactive oxygen species induced by irradiation.

  8. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    SciTech Connect

    Mumbrekar, Kamalesh Dattaram; Fernandes, Donald Jerard; Goutham, Hassan Venkatesh; Sharan, Krishna; Vadhiraja, Bejadi Manjunath; Satyamoorthy, Kapaettu; Bola Sadashiva, Satish Rao

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  9. Acute exposure to solar simulated ultraviolet radiation affects oxidative stress-related biomarkers in skin, liver and blood of hairless mice.

    PubMed

    Svobodová, Alena Rajnochová; Galandáková, Adéla; Sianská, Jarmila; Doležal, Dalibor; Ulrichová, Jitka; Vostálová, Jitka

    2011-01-01

    The ultraviolet (UV) region of solar radiation is a critical factor in the initiation and development of a number of skin diseases. However, it is not only skin which is directly exposed to solar light that is affected by UV radiation, through low molecular weight mediators, generated upon irradiation, "non-skin" tissues can also be affected. The aim of this study was to examine in detail, the acute effects of UVA and UVB wavebands on hairless mice. Female SKH-1 hairless mice were exposed to a single dose of UVB (200, 800 mJ/cm(2)) or UVA (10, 20 J/cm(2)) using a solar simulator. The effects on haematological parameters, activity and/or expression of antioxidant enzymes, level of glutathione (GSH), markers of oxidative damage (lipid peroxidation and carbonylated proteins) were analysed in erythrocytes, plasma, liver and whole skin homogenates. No macroscopic changes were observed either 4 or 24 h after UVA/UVB exposure. The blood count showed a significant increase in leukocyte number and reduction of platelets 4 h following UVA and UVB irradiation, which disappeared 24 h after irradiation except for the higher UVA dose. Changes in oxidative stress-related parameters, particularly activity of catalase (CAT) and superoxide dismutase (SOD) and level of GSH and lipid peroxidation products, were found in skin, erythrocytes and liver. The expression of several enzymes (CAT, SOD, glutathione transferase (GST), nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (NQO1) and hem oxygenase-1 (HO-1)) in skin was affected following UVA and UVB radiation. Increase in carbonylated proteins was found in plasma and skin samples.

  10. Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery.

    PubMed

    Terrazzino, Salvatore; La Mattina, Pierdaniele; Masini, Laura; Caltavuturo, Tina; Gambaro, Giuseppina; Canonico, Pier Luigi; Genazzani, Armando A; Krengli, Marco

    2012-05-01

    To evaluate the impact of functional polymorphisms in genes related to DNA repair mechanisms (XRCC1, TP53, MSH2, MSH3, XPD), oxidative stress response (GSTP1, GSTA1, eNOS, SOD2) and fibroblast proliferation (TGFβ1) on the risk of acute skin toxicity in breast cancer patients receiving radiotherapy. Skin toxicity was scored according to the Radiation Therapy Oncology Group criteria in 286 breast cancer patients who received radiotherapy after breast conserving surgery. Genotyping was conducted by PCR-RFLP analysis and real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. In the multivariate analysis, nominally significant associations, before multiple testing corrections, were found between XRCC1 T-77C (T carriers vs. CC, OR: 2.240, 95% CI: 1.015-4.941, P=0.046), eNOS G894T polymorphisms (TT vs. G carriers, OR: 2.473, 95% CI: 1.220-5.012, P=0.012), breast diameter (OR: 1.138, 95% CI: 1.001-1.293, P=0.048), boost dose-fractionation (3 Gy vs. no boost, OR: 4.902, 95% CI: 1.458-16.483, P=0.010) and ≥ grade 2 acute radiation skin toxicity in breast cancer patients. As our exploratory study suggests that XRCC1 T-77C and eNOS G874T may confer an increased risk of acute skin reactions to radiotherapy in breast cancer patients, further confirmatory studies are warranted to determine the clinical significance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Treatment of irritable bowel syndrome.

    PubMed

    Hadley, Susan K; Gaarder, Stephen M

    2005-12-15

    Irritable bowel syndrome affects 10 to 15 percent of the U.S. population to some degree. This condition is defined as abdominal pain and discomfort with altered bowel habits in the absence of any other mechanical, inflammatory, or biochemical explanation for these symptoms. Irritable bowel syndrome is more likely to affect women than men and is most common in patients 30 to 50 years of age. Symptoms are improved equally by diets supplemented with fiber or hydrolyzed guar gum, but more patients prefer hydrolyzed guar gum. Antispasmodic agents may be used as needed, but anticholinergic and other side effects limit their use in some patients. Loperamide is an option for treatment of moderately severe diarrhea. Antidepressants have been shown to relieve pain and may be effective in low doses. Trials using alosetron showed a clinically significant, although modest, gain over placebo, but it is indicated only for women with severe diarrhea-predominant symptoms or for those in whom conventional treatment has failed. Tegaserod has an advantage over placebo in constipation-predominant irritable bowel syndrome; it is indicated for up to 12 weeks of treatment in women. However, postmarketing reports of severe diarrhea and ischemic colitis further limit its use. Herbal therapies such as peppermint oil also may be effective in the treatment of irritable bowel syndrome. Therapies should focus on specific gastrointestinal dysfunctions (e.g., constipation, diarrhea, pain), and medications only should be used when nonprescription remedies do not work or when symptoms are severe.

  12. Disposable baby wipes: efficacy and skin mildness.

    PubMed

    Odio, M; Streicher-Scott, J; Hansen, R C

    2001-04-01

    The results of a series of four clinical studies demonstrated that disposable baby wipes were milder to the skin than use of a cotton washcloth and water, recognized as a "gold standard" for skin mildness. Importantly, the baby wipes caused no significant change from the baseline value in any of the skin par