Linalool - a significant contact sensitizer after air exposure

Background: Linalool is a widely used fragrance terpene. Pure linalool is not allergenic or a very weak allergen, but autoxidizes on air exposure and the oxidation products can cause contact allergy. Oxidized (ox.) linalool has previously been patch tested at a concentration of 2.0% in petrolatum (pet.) in 1511 patients, and 1.3% positive patch test reactions were observed. Objective: To investigate the optimal patch test concentration for detection of contact allergy to ox. linalool. Methods: Four concentrations of ox. linalool (2.0%, 4.0%, 6.0%, 11.0% pet.) were tested in 3418 consecutive dermatitis patients. Results: Ox. linalool 2.0%, 4.0%, 6.0%, and 11.0% pet. detected positive patch test reactions in 0.83%, 3.2%, 5.3%, and 7.2% of the tested patients, respectively. The doubtful reactions increased with rising concentrations but relatively less, giving 5.1%, 6.4%, and 7.3% doubtful reactions, respectively, for ox. linalool 4.0%, 6.0%, and 11.0% pet. Few irritative reactions were seen. Conclusions: Raising the patch test concentration for ox. linalool gave a better detection of contact allergy, as many as 5-7% positive patch test reactions were detected. We suggest a patch test concentration of ox. linalool 6.0% pet. for future patch testing, giving a dose per unit area of 2.4 mg/cm(2) when 20 mg test substance is tested in small Finn Chambers (R)

Apo-14´-Carotenoic acid is a novel endogenous and bioactive apo-carotenoid

Carotenoids can be metabolized to various apo-carotenoids and retinoids. Apo-15´-carotenoic acid (retinoic acid, RA) is a potent activator of the retinoic acid receptor (RAR) in its all-trans- (ATRA) and 9-cis- (9CRA) forms. In this study we show firstly, that apo-14´-carotenoic acid (A14CA), besides retinoic acids, is present endogenously and with increased levels in the human organism after carrot juice supplementation rich in β-carotene. All-trans-A14C (ATA14CA) is just a moderate activator of RAR-transactivation in reporter cell lines but can potently activate retinoic acid response element (RARE)-mediated signalling in DR5/RARE-reporter mice and potently increase retinoid-reporter target gene expression in ATA14CA-supplemented mice and treated MM6 cells. Further metabolism to all-trans-13,14-dihydroretinoic acid (ATDHRA) may be the key for its potent effects on retinoid target gene activation in ATA14CA-treated MM6 cells and in liver of supplemented mice. We conclude that besides RAs, there are alternative ways to activate RAR-response pathways in the mammalian organism. ATA14CA alone and in combination with its metabolite ATDHRA may be an alternative pathway for potent RAR-mediated signalling.Ministerio de Economía y Competitividad (España) | Ref. SAF2016-77620-R-FEDERXunta de Galicia | Ref. GRC ED431C 2017/6

Transcriptomic and lipidomic profiling of eicosanoid/ docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients

Lipoxygenases (LOX) and cyclooxygenase (COX) are the main enzymes for PUFA metabolism to highly bio‐active prostaglandins, leukotrienes, thromboxanes, lipoxins, resolvins and protectins. LOX and COX pathways are important for the regulation of pro‐inflammatory or pro‐resolving metabolite synthesis and metabolism for various inflammatory diseases such as atopic dermatitis (AD). In this study, we determined PUFAs and PUFA metabolites in serum as well as affected and non‐affected skin samples from AD patients and the dermal expression of various enzymes, binding proteins and receptors involved in these LOX and COX pathways. Decreased EPA and DHA levels in serum and reduced EPA level in affected and non‐affected skin were found; in addition, n3/n6‐PUFA ratios were lower in affected and non‐affected skin and serum. Mono‐hydroxylated PUFA metabolites of AA, EPA, DHA and the sum of AA, EPA and DHA metabolites were increased in affected and non‐affected skin. COX1 and ALOX12B expression, COX and 12/15‐LOX metabolites as well as various lipids, which are known to induce itch (12‐HETE, LTB4, TXB2, PGE2 and PGF2) and the ratio of pro‐inflammatory vs pro‐resolving lipid mediators in non‐affected and affected skin as well as in the serum of AD patients were increased, while n3/n6‐PUFAs and metabolite ratios were lower in non‐affected and affected AD skin. Expression of COX1 and COX‐metabolites was even higher in non‐affected AD skin. To conclude, 12/15‐LOX and COX pathways were mainly upregulated, while n3/n6‐PUFA and metabolite ratios were lower in AD patients skin. All these parameters are a hallmark of a pro‐inflammatory and non‐resolving environment in affected and partly in non‐affected skin of AD patients

Patch Testing with a Textile Dye Mix in Two Concentrations : A Multicentre Study by the Swedish Contact Dermatitis Research Group

Disperse dyes, which are used for colouring synthetic textile fibres, are well-known contact sensitisers. To investigate the outcome of patch-testing with a textile dye mix (TDM) at 7 dermatology clinics in Sweden, a TDM tested at 2 concentrations was included into the baseline series during one year. The mix consisted of Disperse (D) Blue 35, D Yellow 3, D Orange 1 and 3, D Red 1 and 17, all 1.0%, and D Blue 106 and D Blue 124, each 0.3% in the mix 6.6% and 1.0% each in the mix 8.0%. In 2,122 tested patients, contact allergy to the TDM at the concentration 8.0% was found in 2.8% and to the TDM at 6.6% in 2.5% of the patients. The contact allergy to the TDM could explain or contribute to the dermatitis in about 35% of the patients. Conclusion: contact allergy to the TDM is common and inclusion into the Swedish baseline series should be considered

Patch Testing with a Textile Dye Mix in Two Concentrations : A Multicentre Study by the Swedish Contact Dermatitis Research Group

Disperse dyes, which are used for colouring synthetic textile fibres, are well-known contact sensitisers. To investigate the outcome of patch-testing with a textile dye mix (TDM) at 7 dermatology clinics in Sweden, a TDM tested at 2 concentrations was included into the baseline series during one year. The mix consisted of Disperse (D) Blue 35, D Yellow 3, D Orange 1 and 3, D Red 1 and 17, all 1.0%, and D Blue 106 and D Blue 124, each 0.3% in the mix 6.6% and 1.0% each in the mix 8.0%. In 2,122 tested patients, contact allergy to the TDM at the concentration 8.0% was found in 2.8% and to the TDM at 6.6% in 2.5% of the patients. The contact allergy to the TDM could explain or contribute to the dermatitis in about 35% of the patients. Conclusion: contact allergy to the TDM is common and inclusion into the Swedish baseline series should be considered

Patch testing with formaldehyde 2.0% in parallel with 1.0% by the Swedish Contact Dermatitis Research Group

In a multicentre study consecutively patch-tested dermatitis patients were tested simultaneously with 1.0% and 2.0% (w/v) formaldehyde in aqua applied with a micropipette (15 µl) to the filter paper disc in Finn Chambers (0.30 mg/cm2 and 0.60 mg/cm2, respectively). A total of 2,122 dermatitis patients were patch-tested. In all, 77 (3.6%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 35 reacted to both concentrations and 5 patients reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde with 2.0% compared to 1.0% (p < 0.001) without causing more irritant reactions. The detected number of isolated allergic reactions to the 2 formaldehyde-releasers in the Swedish baseline series and not to formaldehyde itself raises the question whether quaternium-15 1.0% and diazolidinyl urea 2.0% should be present in the Swedish baseline series

Patch testing with formaldehyde 2.0% in parallel with 1.0% by the Swedish Contact Dermatitis Research Group

In a multicentre study consecutively patch-tested dermatitis patients were tested simultaneously with 1.0% and 2.0% (w/v) formaldehyde in aqua applied with a micropipette (15 µl) to the filter paper disc in Finn Chambers (0.30 mg/cm2 and 0.60 mg/cm2, respectively). A total of 2,122 dermatitis patients were patch-tested. In all, 77 (3.6%) patients reacted positively to formaldehyde; 37 reacted only to 2.0%, 35 reacted to both concentrations and 5 patients reacted only to 1.0%. Significantly more patients were thus diagnosed with contact allergy to formaldehyde with 2.0% compared to 1.0% (p < 0.001) without causing more irritant reactions. The detected number of isolated allergic reactions to the 2 formaldehyde-releasers in the Swedish baseline series and not to formaldehyde itself raises the question whether quaternium-15 1.0% and diazolidinyl urea 2.0% should be present in the Swedish baseline series