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Darbo tikslas – įvertinti dermatitu sergančių pacientų įsijautrinimą kontaktiniams alergenams ir su juo susijusius veiksnius. Darbo uždaviniai: 1. Nustatyti įsijautrinimo kontaktiniams alergenams dažnumą tarp dermatitu sergančių pacientų. 2. Įvertinti įsijautrinimo kontaktiniams alergenams dažnumo sąsajas su tiriamųjų amžiumi, lytimi ir profesija. 3. Nustatyti įsijautrinimo kontaktiniams alergenams klinikos ypatumus. 4. Įvertinti įsijautrinimo kontaktiniams alergenams sąsajas su atopiniu dermatitu, lėtine (-ėmis) kojos (-ų) opa (-omis) ir kitais veiksniais. Išvados: 1. Kontaktiniams alergenams įsijautrinę pusė dermatitu sergančių pacientų, dažniausiai – metalui nikeliui (17,1 proc.). Iš aromatinių medžiagų dažniausias yra įsijautrinimas Peru balzamui (8 proc.). Į pagrindinį alergenų rinkinį neįtrauktini retai (0,1 proc.) nustatyti alergenai: gumų medžiagos merkaptobenzotiazolas ir N-zopropil-N’-fenil-parafenilendiaminas. 2. Įsijautrinimas kontaktiniams alergenams jaunesniems nei 40 metų dermatitu sergantiems pacientams pasireiškia du kartus dažniau nei vyresniems, o moterims – du kartus dažniau nei vyrams. Žemės ūkio ir miškininkystės darbuotojai kontaktiniams alergenams įsijautrinę tris kartus dažniau nei kiti dirbantieji. Vertinant atskirus alergenus, jaunesni nei 40 metų pacientai dažniau nei vyresni yra įsijautrinę nikeliui, kobaltui ir kvaterniumui-15, o 40 metų ir vyresni – Peru balzamui, kanifolijai, aromatų mišiniui I, lanolinui, seskviterpenlaktonams ir... [toliau žr. visą tekstą] / The aim of the study: To evaluate contact sensitization and its associated factors in patients with dermatitis. The objectives of the study: 1. To determine the frequency of sensitization to contact allergens in patients with dermatitis. 2. To evaluate associations between the frequency of sensitization to contact allergens and age, sex and occupation in patients with dermatitis. 3. To determine clinical features of contact sensitization. 4. To evaluate associations between sensitization to contact allergens and atopic dermatitis, chronic leg ulcers and other factors. CONCLUSIONS 1.Half of the patients with dermatitis were sensitized to contact allergens, most frequently to metal nickel (17.1%). From the fragrances, bal¬sam of Peru was the most frequent contact allergen (8%). Rare allergens that should not be included in the baseline series are the substances present in the composition of rubber – mercaptobenzothiazole and N-isopropyl-N'-phenyl-p-phenylene diamine (IPPD). 2.Patients under 40 years of age are two times more frequently sensitized than the older ones. In women contact allergy is twice as more frequent as in men. Agricultural and forestry workers are sensitized to contact allergens three times as more often as other employees. What regards individual allergens, among patients under 40 years of age sensitization to nickel, cobalt and quaternium-15 is more prevalent than in the older ones. Among patients who are 40 years of age and over contact sensitization to... [to full text]

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Orientador: Luciana Patrícia Fernandes Abbade / Resumo: Introdução: Úlceras crônicas de membros inferiores são muito prevalentes. O tratamento local é feito através do uso de curativos específicos e outros produtos tópicos. A utilização destes podem causar dermatite de contato alérgica, aumentando a morbidade relacionada à doença e retardo da cicatrização. Objetivos: Identificar a frequência e principais substâncias alergênicas relacionadas à dermatite de contato nos pacientes portadores de úlceras crônicas nos membros inferiores. Métodos: Estudo observacional, com desenho transversal, realizado em 64 pacientes com diagnóstico de úlcera crônica de membros inferiores ativa ou cicatrizada independente da etiologia. Em todos os participantes foi realizado o teste de contato com a bateria padrão e com os curativos e produtos frequentemente utilizados para tratamento destas úlceras. Foram avaliadas variáveis clínicas e as relacionadas ao teste de contato. Resultados: Eczema peri-úlcera estava presente em 50 pacientes (78,1%). O teste de contato padrão foi positivo em 28 participantes (43,8%), sendo o paraben mix, sulfato de níquel e lanolina as substâncias do teste padrão que mais positivaram. O teste de contato com os curativos e produtos foi positivo em 17 participantes (25,6%) e os principais alérgenos foram, em ordem decrescente: colagenase com cloranfenicol (16%), sulfadiazina de prata (13%) e bota de Unna (6%). Eczema peri-úlcera relacionou-se positivamente com o uso de colagenase e hidratantes. Conclusão: A positividade ao teste... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Chronic leg ulcers are very prevalent and the local treatment is done through the use of specific dressings and other topical products. The use of these can cause allergic contact dermatitis, increasing disease-related morbidity and delayed healing. Objective: To identify the frequency and the main allergenic substances related to contact dermatitis in patients with chronic leg ulcers. Methodology: Observational study, with transversal design, performed with 64 patients diagnosed with active or healed chronic leg ulcers regardless of etiology were included. Patch tests were performed with all the patients, including the standard battery and the dressings and products frequently used on the treatment. Clinical variables and those related to the patch test were evaluated. Results: Peri-wound eczema was present in 50 patients (78.1%). The standard patch test was positive in 28 (43.8%) participants, with paraben mix, nickel sulfate and lanolin being the most positive substances. The patch test with dressings and products was positive in 17 (25.6%) participants and the main allergens were, in decreasing order: collagenase with chloramphenicol (16%), silver sulfadiazine (13%) and Unna's boot (6%). Peri-wound eczema was positively related to the use of collagenase and moisturizers. Conclusion: Positive patch test in patients with chronic leg ulcers is still high and peri-wound eczema, an important comorbidity that delays healing, is at increased risk in patients using ... (Complete abstract click electronic access below) / Mestre

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Diss. (sammanfattning) Stockholm : Karol inst., 2004. / Härtill 5 uppsatser.

Les sensibilisants de contact sont des molécules réactives électrophiles qui ont la capacité de modifier des protéines de la peau pour former un antigène. Au delà de ce mécanisme d'hapténisation, le signal de danger induit par les sensibilisants conduisant à l'activation des cellules dendritiques (DC) est un élément déterminant dans l'induction de cellules T spécifiques de l'haptène. Dans le contexte du 7ième amendement à la directive cosmétique européenne, la mise en place d'une batterie de tests in vitro permettant de prédire le potentiel sensibilisant de molécules est indispensable pour l'industrie cosmétique. Tandis que la plupart des études in vitro étudient les signaux de danger induits par les sensibilisants dans des modèles homéostasiques, nous nous sommes intéressés à l'effet des sensibilisants sur la mise en place d'une réponse inflammatoire. Lorsque la lignée U937 est différenciée avec du PMA et stimulée avec du LPS, les facteurs de transcription NF-κB et Nrf2 sont activés et l'acide arachidonique (AA) est métabolisé au travers de la cascade cPLA2 / COX-2. L'ensemble de ces voies activées conduit à la production par les U937 d'un grand nombre de médiateurs inflammatoires (IL-1β, TNF-α, IL-6, IL-10, IL-8, PGE2, PGD2, TxB2). Dans ce modèle, nous avons analysé l'effet de 6 sensibilisants de potentiels variés (DNCB, PPD, HQ, PG, CIN, EUG) et montré que de façon inattendue, tous les sensibilisants étudiés diminuent significativement et de façon spécifique la production de tous les prostanoïdes et en particulier de PGE2 induite par PMA/LPS. Nous avons de plus démontré que selon les sensibilisants, les cibles de cette inhibition au sein de la cascade métabolique de l'AA diffèrent, même si elles se focalisent la plupart du temps (sauf pour le DNCB) sur l'enzyme COX-2 (inhibition de son expression et/ou de son activité). Pour le DNCB, le mécanisme d'inhibition semble plutôt impliquer sa capacité à réagir fortement avec les groupements résidus thiols, ce qui se traduit en particulier par la déplétion du GSH intracellulaire et engendrerait l'inhibition des synthases dépendantes du GSH pour leurs activités. En parallèle de cette étude mécanistique, nous avons appréhendé la problématique du point de vue statistique et vérifié sur un set plus important et diversifié de molécules (160 molécules) que le paramètre « inhibition de PGE2 » pouvait être un bon test de prédiction de l'HSRC. L'étude statistique a permis de déterminer le modèle prédictif du test PGE2 et de mettre en évidence de bonnes performances (78%) par rapport aux prédictions du LLNA. Au-delà, une certaine complémentarité du test PGE2 avec d'autres tests in vitro (MUSST, Nrf2-HTS) a pu être mise en évidence. En conclusion, au travers de cette étude, nous avons pu mettre en évidence de nouvelles propriétés biochimiques des sensibilisants. Même si la signification biologique de la diminution de PGE2 par les sensibilisants de contact demeure complexe d'interprétation, ce paramètre a permis le développement d'un test qui prédit avec de bonnes performances le caractère sensibilisant de molécules et dont la position au sein d'une batterie prédictive d'évaluation de l'allergie de contact reste à être précisée. / Contact sensitizers are defined as reactive molecules (electrophilic) which have the ability to modify skin proteins to form an antigen (hapten). In addition to the haptenation mechanism, danger signals, leading to the activation of dendritic cells, are described to be crucial for the effective induction of an hapten-specific T cell immune response. In the context of the 7th amendment to the Cosmetic Directive, the cosmetic industry is concerned by the challenge of finding non-animal approaches to assess the sensitizing potential of chemicals. While danger signals induced by sensitizers in steady-state conditions have already been analyzed, we chose to investigate the impact of sensitizers on the course of an inflammatory response. For this purpose we used the U937 cell line differentiated with PMA and activated with LPS. In these conditions, cells produce a large amount of inflammatory mediators (IL-β, TNF-α, IL-6, IL-10, IL-8, PGE2, PGD2, TxB2) through the activation of pathways leading to the activation of the transcription factors NF-κB and Nrf2 and through AA metabolism by the cPLA2/COX-2 cascade. Interestingly, we showed that 6 contact sensitizers with various potential (DNCB, PPD, HQ, PG, CIN, EUG) significally and specifically decrease the production of prostanoïds and in particular of PGE2 induced by PMA/LPS. We further demonstrated that there is no unique inhibition profile of the sensitizers even if the majority (except for DNCB) of the effects applies on COX-2 (i.e. inhibition of the expression and/or activity). For DNCB, inhibition mechanism appears to be dependant of its capacity to react with thiols residues and in particular to deplete intracellular glutathione possibly leading to the inactivation of the PG-synthases. In parallel, we assess a statistical analysis on 160 molecules that allow us to define the test parameters (a molecule is a sensitizer if the PGE2 inhibition at 24h is more than 60%) and to calculate the test performance toward LLNA (78%). Moreover we demonstrated that the PGE2 test could be complementary to other already existing in vitro tests like MUSST or Nrf2-HTS. In summary, we add here a new insight into the multiple biochemical effects described so far for sensitizers. Even if the underlying biological relevance remains unclear, the parameter “PGE2 inhibition” is good test for skin sensitization evaluation. Further studies will precise how this parameter could be implemented into an alternative testing strategy for the evaluation of skin sensitization.

The aim of the diploma thesis was to provide an overview of the prevalence of allergenic and potentially allergenic metals in eye shadows. The diploma thesis gives an overview of the legislation on cosmetics and description of the types of allergenic reactions caused by allergenic and potential allergenic metals in eye shadows. Listed below are the preparation methods of the samples for analysis and the list of the methods by which can the selected metals be analyzed. The experimental part of the diploma thesis deals with an analysis of selected allergenic and potentially allergenic metals in eye shadows. In the experimental part of diploma thesis method of sample preparation for analysis of eye shadows and a method of analysis of sample of eye shadows by ICP-MS have been optimized. Monitored analytes were selected metals. Altogether 6 samples of eye shadows from different manufacturers were chosen. Measured results have been statistically processed, confronted with the applicable legislation and assessed in terms of possible allergic reactions.

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L’allergie de contact est une pathologie touchant de 15 à 20 % de la population occidentale. A l’heure actuelle il n’existe aucun traitement, la seule façon efficace de prévention étant l’éviction totale des allergènes. Les tests de sensibilisation de nouvelles molécules avant leur mise sur le marché ont été réalisés sur l’animal jusqu’à l’interdiction dans le 7ème amendement à la directive Européenne concernant l’industrie cosmétique. Dans ce contexte il est primordial de développer des méthodes alternatives. Ce travail de thèse propose d’analyser la problématique de l’allergie de contact en allant de la molécule au tissu pour les allergènes réagissant par voie radicalaire :In chemico : étude de la réactivité des hydroperoxydes allyliques vis-à-vis des acides aminés par la RMNIn situ : études de radicaux issus de ces composés sur des épidermes humains reconstitués par RPEIn cellulo : étude du stress oxydant sur les cellules dendritiques et la voie de signalisation Keap1/Nrf2/ARE. / Allergic contact dermatitis is a pathology affecting 15 to 20% of the Western population. Until now no treatment exists, the prevention is the eviction of allergens. In the past, tests concerning new molecules for the market were tested on animals until the prohibition in the 7th amendment of the European directive concerning the cosmetics industry. In this context it is essential to develop alternative methods to assess the allergenic potential of chemicals.This manuscript proposes to analyze the problem of the allergic contact dermatitis from the molecule to the tissue for allergens reacting through radical mechanisms:In chemico: study of the reactivity profile of allylic hydroperoxides toward amino acids by NMRIn situ: radical intermediates formation on reconstructed human epidermis from allylic hydroperoxides by EPR In cellulo: study of the oxidative stress from allylic hydroperoxides on dendritic cells trough the Keap1/Nrf2/ARE sensor pathway.