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Detlef Becker

Publications and source records attributed to Detlef Becker.

11 recordsLinked to original sources
PubMed2006

Patch testing with components of water-based metalworking fluids: results of a multicentre study with a second series.

BACKGROUND: Although many allergens in metalworking fluids (MWF) are identified, there are still some MWF components, which are not sufficiently investigated concerning their sensitizing properties. OBJECTIVES: To investigate sensitization to 10 frequently used MWF components, which are not part of the established MWF test series, in metalworkers with suspected occupational dermatitis due to MWF. PATIENTS/METHODS: Oleyl alcohol, myristyl alcohol, dimethylolurea, 4,4'-methylenebis morpholine, imazalil, 1-amino-2-propanol (monoisopropanolamine; MIPA), 2-amino-2-ethyl-1,3-propanediol (AEPD), 2,5-bis(n-octyldithio)-1,3,4-thiadiazole, zinc alkyl dithiophosphate and dibenzyl disulfide have been patch tested in 144 patients. RESULTS: 7 patients reacted positively to the formaldehyde releaser 4,4'-methylenebis morpholine, and 6 of these patients also reacted to formaldehyde and/or other formaldehyde releasers. 4 patients reacted positively to myristyl alcohol tested at 10% petrolatum (pet.). Additionally, 20 doubtful or irritant reactions occurred. 1 patient each reacted positively to oleyl alcohol, MIPA, and AEPD. None of the other test substances mentioned above elicited any clear-cut positive reaction. Patch testing with well-known MWF allergens showed proportions of positive reactions, which were comparable to those from other studies, e.g. 11% to monoethanolamine, 8% to colophonium and 3%-5% to various preservatives. CONCLUSIONS: 4,4'-methylenebis morpholine may be an important MWF allergen, although clinical relevance could not be stated definitely in every case. Myristyl alcohol should not be patch tested at 10% pet., but at a lesser concentration, due to irritant properties.

Adult↗
PubMed2004

Patch test results with the metalworking fluid series of the German Contact Dermatitis Research Group (DKG).

Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch, in 2001, the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with currently and previously used components, respectively. After 2 years of patch testing, we present results obtained with these series, based on data of the Information Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch tested because of suspected MWF dermatitis in 2002 and 2003 were included in this retrospective data analysis. Of these, 206 were tested with the current MWF series and 155 with the historical MWF series. Among the current MWF allergens, monoethanolamine ranked 1st with 11.6% positive reactions. Diethanolamine (3.0%), triethanolamine (1.1%), and diglycolamine (1.9%) elicited positive reactions far less frequently. Allergic reactions to p-aminoazobenzene were frequently observed (6.0%), but the relevance of these reactions is still obscure. Positive reactions to biocides ranged from 4.5% for Bioban CS 1135 to 0.5% for iodopropynyl butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde, which caused positive reactions in 3.3%, and formaldehyde releasers occurred to varying extents without conclusive pattern. No positive reactions were seen to dibutyl phthalate, di-2-ethylhexyl phthalate, tricresyl phosphate, isopropyl myristate or benzotriazole. With the historical MWF test series, positive reactions to methyldibromo glutaronitrile (MDBGN) were observed most frequently. However, sensitization via allergen sources other than MWF seems likely, as MDBGN, during the study period, has been one of the most frequent preservative allergens in cosmetics and body care products. Other historical MWF allergens comprised morpholinyl mercaptobenzothiazole (3.3%), benzisothiazolinone (BIT; 2.0%) and Bioban P 1487(1.3%). BIT is currently used in MWF again, so it was shifted to the current MWF test series. As decreasing reaction frequencies to former MWF allergens that are no longer used can be expected, the historical series should be re-evaluated after some years. The test series with current MWF allergens has to be kept up-to-date based on information from industry and to be kept concise by eliminating test substances which never cause positive reactions.

Adolescent↗
PubMed2003

Coupling of contact sensitizers to thiol groups is a key event for the activation of monocytes and monocyte-derived dendritic cells.

Strong contact sensitizers are able to induce distinct signal transduction mechanisms in antigen-presenting cells by coupling to cell proteins. The predominant target structures of haptens are thought to be thiol and amino groups in cysteine and lysine residues. We studied whether coupling of small reactive chemicals to thiol or amino groups might be responsible for the activation of monocytes and mature monocyte-derived dendritic cells. Human peripheral blood mononuclear cells were stimulated in vitro with subtoxic concentrations of the strong haptens 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone and 2, 4, 6-trinitrochlorobenzene, the thiol-reactive reagents N-hydroxymaleimide and N-ethylmaleimide, as well as the amino-reactive compounds sulfosuccinimidyl acetate and 2-iminothiolane. Flow cytometric quantification of tyrosine phosphorylation in CD14+ monocytes showed that 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone, 2, 4, 6-trinitrochlorobenzene, N-hydroxymaleimide, and N-ethylmaleimide but not sulfosuccinimidyl acetate and 2-iminothiolane strongly induced this process. Tyrosine phosphorylation induced by 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone and 2, 4, 6-trinitrochlorobenzene was completely prevented in the presence of cysteine but not lysine, suggesting a competitive mechanism between cysteine and sulfhydryl groups of cell proteins. Using the mouse ear swelling test N-hydroxymaleimide could be classified as a significant contact allergen in comparison to 2, 4, 6-trinitrochlorobenzene, whereas no sensitizing potential became apparent for sulfosuccinimidyl acetate and 2-iminothiolane. Western blot analysis on monocytes and mature monocyte-derived dendritic cells confirmed the flow cytometric data for tyrosine phosphorylation and demonstrated a selective capacity of haptens and thiol-reactive compounds to activate ERK1/2 mitogen-activated protein kinase. Our data show that strong affinity of a small reactive chemical toward thiol groups is important for the activation of monocytes and monocyte-derived dendritic cells and can support the process of sensitization.

Acetates↗
PubMed2003

Thiol antioxidants block the activation of antigen-presenting cells by contact sensitizers.

Strong contact sensitizers are able to induce signal transduction mechanisms such as tyrosine phosphorylation and activation of MAP kinases in antigen-presenting cells. We studied the capacity of different antioxidants (ascorbic acid, alpha-tocopherol, pyrrolidine dithiocarbamate, N-acetylcysteine, and glutathione) to block the increase in tyrosine phosphorylation in human monocytes seen after stimulation with strong contact sensitizers. Human peripheral blood mononuclear cells were stimulated with 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone in the presence or absence of these antioxidants. The total amount of membrane-associated phosphotyrosine in CD14+ cells was quantified using flow cytometric techniques. Complete inhibition of tyrosine phosphorylation was noticed when cells were stimulated in the presence of N-acetylcysteine or glutathione. Using N-acetylcysteine as inhibitor similar results were obtained for cells stimulated with formaldehyde, thimerosal methyldibromoglutaronitrile, diphenylcyclopropenone, p-phenylenediamine, toluene-2,5-diamine, and 2,4-dinitrofluorobenzene. By use of a trinitrophenyl-specific monoclonal antibody it was shown that N-acetylcysteine as well as cysteine prevents the binding of 2,4,6-trinitrochlorobenzene to proteins in monocytes and monocyte-derived mature dendritic cells. Furthermore, the capacity of N-acetylcysteine to block the activation of p38 and ERK1/2 MAP kinases by 2,4,6-trinitrochlorobenzene was demonstrated. The radical scavengers ascorbic acid and alpha-tocopherol as well as the nuclear factor kappaB inhibitor pyrrolidine dithiocarbamate failed to prevent the increase in tyrosine phosphorylation. Our data present evidence that reactive oxygen species as well as transcription factor nuclear factor kappaB seem to be unimportant for the induction of tyrosine phosphorylation by contact sensitizers. On the other hand, protection of thiol groups using compounds with free sulfhydryl groups is very effective to block this process. This finding may have implications for prevention of occupational sensitization to strong contact allergens.

Acetylcysteine↗
PubMed2003

Patch testing with components of water-based metalworking fluids.

Water-based metalworking fluids (MWFs) may cause both irritant and allergic contact dermatitis. Several well-known MWF allergens are available for patch testing, but considering the wide variety of possible components used in MWF, our diagnostic arsenal covers only a small part of potential allergens. We therefore selected 13 frequently used MWF components that might be sensitizers and had not yet been tested routinely. In 5 centres, 233 dermatitis patients with present or past occupational exposure to MWF were patch tested with this and other panels. Only 7 patients showed positive reactions to the study panel. Allergic reactions to the emulsifier diglycolamine [syn. 2-(2-aminoethoxy) ethanol] were seen in 5 patients, and 1 patient each reacted positively to 2-amino-2-ethyl-1,3-propanediol (AEPD) and methyldiethanolamine (MDEA). Clinical relevance of the reactions to diglycolamine was unequivocally proven by its presence in the MWF from the patients' workplace in 3 cases. Diglycolamine seems to be an important MWF allergen, independently from monoethanolamine and diethanolamine. A test concentration of 1% petrolatum (pet.) appears to be appropriate. The importance of AEPD and MDEA as MWF allergens still remains to be established. The lack of positive test reactions to the other MWF components tested may be due to their low-sensitizing potential or too low a patch test concentration being used.

Adult↗
PubMed2002

JAK/STAT pathways are not involved in the direct activation of antigen-presenting cells by contact sensitizers.

JAK/STAT pathways are described as the major mechanisms by which cytokine receptors transduce intracellular signals. The signalling mechanisms in antigen-presenting cells (APC) in the sensitization phase of contact hypersensitivity are poorly understood. The aim of this study was to clarify whether well-established JAK/STAT signalling pathways might be activated directly by contact sensitizers as described previously for tyrosine kinases and some MAP kinases. As a model of epidermal APC, human monocytes and human monocyte-derived dendritic cells were stimulated with the structurally unrelated contact sensitizers MCI/MI, thimerosal, TNCB and formaldehyde. The phosphorylation states of the transcription factors STAT1, STAT3, STAT4, STAT5 and STAT6 were determined by Western blot analysis using phosphospecific antibodies. In contrast to the positive controls performed with the cytokines IFN-gamma, IL-10, IFN-alpha, GM-CSF and IL-4, no significant increase in the phosphorylation of STAT molecules was recognized in hapten-treated cells. These results suggest that contact allergens do not directly activate common JAK/STAT pathways. Therefore the activation of APC in the early sensitization phase of contact hypersensitivity by haptens does not involve signals normally delivered by JAK-associated cytokine receptors.

Antigen-Presenting Cells↗
PubMed2002

Activation and translocation of p38 mitogen-activated protein kinase after stimulation of monocytes with contact sensitizers.

Recently we described the induction of tyrosine phosphorylation by contact sensitizers as an early molecular event during the activation of antigen- presenting cells. In this study, the role of the p38 mitogen-activated protein kinase for the activation of human monocytes after exposure to four structurally unrelated contact sensitizers was analyzed in comparison with the irritant benzalkonium chloride and an inductor of oxidative stress (H2O2) using immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay techniques. Bio chemical analysis revealed a translocation of p38 from the cytoplasm to the detergent-resistant cell fraction only upon stimulation with contact sensitizers. The activity of p38 was studied by quantification of its phosphorylated active form with a specific antibody and by kinase assay. Although all stimulants used in this study led to the activation of p38, a translocation to the detergent-resistant fraction as well phosphorylation of the mitogen-activated protein kinase dependent transcription factor Elk-1 was induced only by contact sensitizers. Evidence for a functional relevance of mitogen-activated protein kinase activation was provided by measurement of the hapten-induced production of the proinflammatory cytokine interleukin-1beta. Its release was inhibited by blocking p38-mediated signaling using the imidazole compounds SB203580 and SB202190. These data show that contact sensitizers are strong activators of the p38 mitogen-activated protein kinase. Although activation of this stress-associated pathway has been reported for many other stimuli, a unique translocation of p38 from the cytoplasm to the detergent-resistant fraction seems to be a specific event during hapten-induced activation of antigen-presenting cells.

Benzalkonium Compounds↗
PubMedDate not supplied

The MOAHLFA index of irritant sodium lauryl sulfate reactions: first results of a multicentre study on routine sodium lauryl sulfate patch testing.

In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25% and 0.5% aq. has been added to routine allergen patch tests to assess its properties as a convenient diagnostic indicator of individual susceptibility to irritation at the time of patch testing. Previous studies indicated that irritant SLS reactivity may be related to individual factors such as age and sex. As these factors are, in turn, among the important predictors of contact allergy to many allergens, e.g. summarized in the 'MOAHLFA index', the impact of the MOAHLFA factors on irritant SLS patch test reactivity, and thus a potential for confounding, was assessed in the 5971 participating patients. As a result of 2 logistic regression analyses with an irritant reaction to 0.25% and 0.5% SLS, respectively, as outcome, male sex was identified as a relatively weak but significant risk factor (OR 1.38), while age 40 years or older was an even weaker risk factor (OR 1.22 and 1.15, respectively). Upon detailed analysis, no clear age gradient could, however, be identified. 1-day exposure time almost halved the odds of an irritant SLS reaction. In conclusion, this type of SLS patch test can be regarded as robust, indicating individual irritability relatively independent from the individual factors analysed here.

Adult↗