Allergic contact dermatitis from dyes used in the temple of spectacles.

BACKGROUND: We observed an increasing number of patients who presented with facial or retro-auricular dermatitis after skin contact with plastic spectacles or plastic covered temples. OBJECTIVES: To identify the allergens in plastic spectacles that may cause allergic contact dermatitis. METHODS: All patients with suspected allergic contact dermatitis to eyewear were tested with Solvent Orange 60 (SO60), four additionally with Solvent Yellow 14 (SY14), and five with scrapings from their own spectacles. In one case, a chemical analysis of the spectacles was performed to uncover the causative allergen. RESULTS: Three patients were allergic to SO60, two patients to SY14, and two patients were allergic to both SO60 and SY14. CONCLUSION: Patients with suspected allergic contact dermatitis from spectacles should be tested with SO60 and SY14, and based on findings from previous reports, also with Solvent Red 179.

Isolation, Structural Identification, Synthesis, and Pharmacological Profiling of 1,2-trans-Dihydro-1,2-diol Metabolites of the Utrophin Modulator Ezutromid.

5-(Ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (ezutromid, 1) is a first-in-class utrophin modulator that has been evaluated in a phase 2 clinical study for the treatment of Duchenne muscular dystrophy (DMD). Ezutromid was found to undergo hepatic oxidation of its 2-naphthyl substituent to produce two regioisomeric 1,2-dihydronaphthalene-1,2-diols, DHD1 and DHD3, as the major metabolites after oral administration in humans and rodents. In many patients, plasma levels of the DHD metabolites were found to exceed those of ezutromid. Herein, we describe the structural elucidation of the main metabolites of ezutromid, the regio- and relative stereochemical assignments of DHD1 and DHD3, their de novo chemical synthesis, and their production in systems in vitro. We further elucidate the likely metabolic pathway and CYP isoforms responsible for DHD1 and DHD3 production and characterize their physicochemical, ADME, and pharmacological properties and their preliminary toxicological profiles.

S phase arrest in lymphocytes induced by urinary 1-hydroxypyrene and alcohol drinking in coke oven workers.

Arrest of the cell cycle after DNA damage is believed to promote DNA repair. We aim to investigate the main factors affecting cell cycle arrest of lymphocytes in coke oven workers. A total of 600 workers were included in this study, and their urinary levels of four polycyclic aromatic hydrocarbons (PAH) metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and cell cycle distribution were determined. Urinary PAH metabolites were significantly increased in coke oven workers ( p < 0.01). It was found that only urinary 2-hydroxynaphthalene and 1-hydroxypyrene showed significant positive linear dose-response effects on 8-OHdG in this study population ( ptrend = 0.025 and 0.017, respectively). The dose-response effect was also observed for smoking and drinking on 8-OHdG ( ptrend < 0.001 and 0.034, respectively). Multivariate logistic regression analysis revealed that high levels of urinary 1-hydroxypyrene were associated with a significantly increased risk of S phase arrest (odds ratio (OR) = 1.32, p = 0.03), so as heavy alcohol drinking (OR = 1.31, p = 0.02). Drinking can significantly modify the effects of urinary 1-hydroxypyrene on S phase arrest, during co-exposure to both heavy drinking and median or high 1-hydroxypyrene levels (OR = 3.31, 95% confidence interval (CI) = 1.21-7.63 and OR = 2.56, 95% CI = 1.08-6.06, respectively). Our findings demonstrate that coke oven workers with heavy drinking will cause S phase arrest so as to repair more serious DNA damage.

Prenatal urinary polycyclic aromatic hydrocarbon metabolites, global DNA methylation in cord blood, and birth outcomes: A cohort study in China.

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a potential risk factor for adverse birth outcomes. Epigenetic mechanisms may play a key role in which PAHs exert its effects. OBJECTIVE: Our study aimed to examine whether prenatal PAH exposure was associated with adverse birth outcomes and altered DNA methylation and to explore potential mediating roles of DNA methylation. METHODS: Ten urinary PAH metabolites were measured from 106 pregnant women during late pregnancy in a Chinese cohort study. Cord blood DNA methylation in long interspersed nucleotide element-1 (LINE-1) and Alu repetitive elements as surrogates of global DNA methylation was analyzed by bisulfite pyrosequencing. Multivariable linear regression was used to estimate the associations of urinary PAH metabolites with birth outcomes and DNA methylation, and a mediation analysis was also conducted. RESULTS: Prenatal urinary 2-hydroxynaphthalene (2-OHNa), ∑OHNa (sum of 1- and 2-OHNa), and sum of monohydroxy-PAH (∑OH-PAHs) were associated with lower birth length (e.g., -0.80%, 95% CI: -1.39%, -0.20% for the third vs. first tertile of 2-OHNa; p for trend = 0.01). Prenatal urinary 2-OHNa and 1-hydroxyphenanthrene (1-OHPh) were associated with lower Alu and LINE-1 methylation (e.g., -1.88%, 95% CI: -3.73%, -0.10% for the third vs. first tertile tertile of 2-OHNa in Alu methylation; p for trend = 0.04). Mediation analysis failed to show a mediator effect of global DNA methylation in the association between prenatal urinary OH-PAHs and birth outcomes. CONCLUSIONS: Prenatal specific PAH exposures are associated with decreased birth length and global DNA methylation. However, global DNA methylation does not mediate the associations of prenatal PAH exposure with birth outcomes. Further studies are needed to confirm the results.

Single and combined genotoxicity effects of six pollutants on THP-1 cells.

The objective of this study was to evaluate the single and combined genotoxic effects of six food pollutants (Chrysoidine G, Sudan I, acid orange II, malachite green, acrylamide, and potassium bromate) on THP-1 cells through comet assay. The results of the single tests indicated that the pollutants increased the percentage of tail DNA (% tail DNA) in a dose-dependent manner. Moreover, the % tail DNA values induced by synthetic colorants (Chrysoidine G, Sudan I, acid orange II, and malachite green) were significantly higher than those by acrylamide or potassium bromate at most concentrations. In the combined tests, Chrysoidine G (422 µmol/L) or acrylamide (400 µmol/L) was mixed with different concentrations of the other five pollutants respectively. In the first combined tests, most mixtures significantly increased the % tail DNA values with the exception of Chrysoidine G and acid orange II. In the second tests, there were no significant differences in the % tail DNA values between the single and combined tests at most cases.

Orange-Pigmented Sputum as a Manifestation of Smoke Grenade Inhalation Injury.

A 34-year-old man presented with scanty hemoptysis, orange-colored expectoration, and mild dyspnea. He was in an enclosed building taking part in a military training exercise inhaling an orange-colored smoke from a smoke grenade ignition. His symptoms developed immediately after the initial exposure but he sought medical assistance 20 hours later because of their persistence. Fiberoptic bronchoscopy was performed revealing diffuse inflammatory tracheobronchial tree with streaky orange-pigmented secretions in the trachea and both main-stem bronchi. Acute tracheobronchitis was diagnosed and the patient was treated with nebulized bronchodilators and intravenous corticosteroids showing complete recovery. To our knowledge, this is the first well-documented report of inhalation injury induced by a smoke bomb explosion including potassium chlorate oxidizer and Sudan I and presenting with orange-pigmented sputum production. Smoke inhalation injury is associated with significant morbidity and mortality. The heterogeneity of the smoke and the large variety of the resulting symptoms may be the reason why a definition, specific diagnostic criteria, and therapeutic guidelines are still lacking.

Urinary naphthol metabolites and chromosomal aberrations in 5-year-old children.

BACKGROUND: Exposure to naphthalene, an International Agency for Research on Cancer (IARC)-classified possible carcinogen and polycyclic aromatic hydrocarbon (PAH), is widespread, though resulting health effects are poorly understood. Metabolites of naphthalene, 1- and 2-naphthol, are measurable in urine and are biomarkers of personal exposure. Chromosomal aberrations, including translocations, are established markers of cancer risk and a biodosimeter of clastogenic exposures. Although prenatal (maternal) PAH exposure predicts chromosomal aberrations in cord blood, few studies have examined chromosomal aberrations in school-age children and none has examined their association with metabolites of specific PAHs. METHODS: Using Whole Chromosome Paint Fluorescent in situ Hybridization, we documented chromosomal aberrations including translocations, in 113 five-year-old urban minority children and examined their association with concurrent concentrations of PAH metabolites measured in urine. RESULTS: We report that in lymphocytes, the occurrence and frequency of chromosomal aberrations including translocations are associated with levels of urinary 1- and 2-naphthol. When doubling the levels of urinary naphthols, gender-adjusted OR for chromosomal aberrations are 1.63 [95% confidence interval (CI), 1.21-2.19] and 1.44 (95% CI, 1.02-2.04) for 1- and 2-naphthol, respectively; and for translocations OR = 1.55 (95% CI, 1.11-2.17) and 1.92 (95% CI, 1.20-3.08) for 1- and 2-naphthol, respectively. CONCLUSION: Our results show that markers of exposure to naphthalene in children are associated with translocations in a dose-related manner, and that naphthalene may be a clastogen. IMPACT: Indoor exposure to elevated levels of naphthalene is prevalent in large regions of the world. This study is the first to present an association between a marker of naphthalene exposure and a precarcinogenic effect in humans.

Selenium effectively inhibits 1,2-dihydroxynaphthalene-induced apoptosis in human lens epithelial cells through activation of PI3-K/Akt pathway.

PURPOSE: To investigate whether activation of the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (Akt) pathway was necessary for selenium in protecting human lens epithelial cells (hLECs) from 1,2-dihydroxynaphthalene (1,2-DHN)-induced apoptosis. In addition, we studied the link between heat shock protein 70 (HSP70) expression and Akt phosphorylation in selenium-induced cell protection. METHODS: Cell viabilities were assessed by Cell Counting Kit-8 (CCK-8) kit and trypan blue exclusion. The effect of sodium selenite on Akt phosphorylation was studied. After the pretreatment with 30 µM of LY294002, a PI3-K/Akt pathway inhibitor, apoptosis was assessed by flow cytometry, protein levels of phospho-Akt and Akt were quantified by western blot, and cell localization of phospho-Akt was determined by immunofluorescence staining. Time-course effect of sodium selenite on HSP70 expression was studied by reverse transcription polymerase chain reaction (RT-PCR) and western blot. Moreover, effect of LY294002 on HSP70 expression was also examined. RESULTS: Our data showed that sodium selenite increased cell viabilities and prevented 1,2-DHN-induced apoptosis through phosphorylation and nuclear translocation of Akt. Furthermore, pretreatment of LY294002 inhibited the phosphorylation of Akt. However, it failed to block the selenium-induced upregulation of HSP70. CONCLUSIONS: The activation of PI3-K/Akt pathway was necessary for selenium in protecting hLECs from 1,2-DHN-induced apoptosis. However, this pathway was not involved in the selenium-induced upregulation of HSP70.

Safety of high doses of Propionibacterium freudenreichii ET-3 culture in healthy adult subjects.

Propionibacterium freudenreichii ET-3 (7025) culture, a cell-free product of whey fermentation by P. freudenreichii ET-3, has been shown to promote the growth of Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA). Here we report the results of two clinical studies designed to evaluate the safety of high doses of P. freudenreichii ET-3 culture medium. Study 1 had a randomized, double-blind, crossover design. Ten healthy male and four healthy female subjects received 45 tablets of either P. freudenreichii ET-3 culture medium (total daily intake of 3g solid content and 283.5µg of DHNA; active group) or placebo (unfermented product) during two 1-week supplementation periods separated by a 4-week washout period. In Study 2, 11 healthy men took four tablets of P. freudenreichii ET-3 culture medium per day (total daily intake of 0.267g solid content and 22.5µg of DHNA) for a period of 13weeks. In both studies, hematological, clinical chemistry, and urinary parameters were measured before and after each supplementation period and gastrointestinal symptoms were assessed by questionnaire. In Study 1, there were no statistically significant differences between placebo and active supplementation periods in any measured parameter and the incidence of gastrointestinal symptoms were similar between groups. In Study 2, total protein, white blood cell count, hemoglobin, and mean corpuscular hemoglobin concentration decreased significantly from baseline and mean corpuscular volume and urine pH increased from baseline. The changes in hematological parameters were deemed not to be due to P. freudenreichii ET-3 culture medium supplementation given that all parameters remained within normal ranges and were not consistent with any clinically meaningful effect.

Occupational contact dermatitis among the traditional 'tie and dye' cottage industry in Western Rajasthan.

BACKGROUND: Dyeing is an age-old process and forms an integral part of textile industries. Tying is a process by which a particular part of cloth is prevented from the process of dyeing. The skin diseases in workers engaged in the 'tie and dye' industry have not been extensively studied. AIMS: To study the prevalence of contact dermatitis among workers engaged in the 'tie and dye' industries in and around Jodhpur (Western Rajasthan). METHODS: One thousand three hundred workers engaged in 'tie and dye' work were evaluated for occupation-related dermatitis. Those with skin lesions were subjected to patch tests using 2% aqueous solution of the dyes and chemicals commonly used by them. These included direct dyes, VAT dyes, sulfur dyes and azo dyes. Fifty workers without skin lesions served as controls. RESULTS: One hundred patients (7.69%) had dermatitis involving the exposed sites, mainly the hands and forearms. Eighty-one patients showed positive reactions to one or more dyes, most commonly Red RC base (azo dye), followed by naphthol. CONCLUSION: Red RC base and naphthol were the commonest allergens in the 'tie and dye' industry.

Purification and characterization of an allergy-induced melanogenic stimulating factor in brownish guinea pig skin.

We have demonstrated recently that phenylazonaphthol (PAN) allergy-induced hyperpigmentation in brownish guinea pig skin is associated with the concomitant appearance of a melanogenic soluble factor(s) that activates the intracellular signal transduction system, including phosphatidylinositol turnover subsequent to ligand-receptor binding in cultured guinea pig melanocytes. In this study we have purified and characterized the PAN-induced melanogenic stimulating factor (PIMSF) that occurs in allergy-associated hyperpigmented skin. By successive column chromatography on TSK 2000SW, Mono Q, and octadecyl-NPR, the PIMSF was purified to homogeneity with a single band of apparent molecular mass of 7.9 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The specific bioactivity of PIMSF increased by 5,195-fold over the original skin homogenate. In cultured guinea pig melanocytes, this purified PIMSF had the potential of activating an intracellular signal transduction system such as inositol 1,4,5-trisphosphate formation and intracellular calcium levels through a pertussis toxin-sensitive G protein-coupled receptor. PIMSF consistently caused a rapid translocation of cytosolic protein kinase C (PKC) to membrane-bound PKC within 5 min of treatment with a return to the basal level after 120 min. The stimulating effects of PIMSF on proliferation and melanization of cultured guinea pig melanocytes were abolished completely by a PKC down-regulating agent (phorbol 12,13-dibutyrate). PIMSF was similar in molecular mass to rat growth-related oncogene alpha (GRO-alpha; molecular mass of 7.9 kDa) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and had immunocross-reactivity with GRO-alpha upon Western immune blotting analysis. Further, the stimulatory effect of purified PIMSF on DNA synthesis of cultured guinea pig melanocytes was suppressed markedly by the addition of anti-rat GRO-alpha antibody, implying that the PIMSF is apparently identical to GRO-alpha. These findings suggest that PAN allergy provides a new mechanism of hyperpigmentation in which biological factors such as the GRO-alpha superfamily generated within allergy-induced skin stimulate melanocytes through activation of the PKC-related signal transduction pathway.

[Delayed type allergic reaction to red azo dye in tattooing]. / Allergische Spättypreaktion auf roten Azofarbstoff in Tätowierungen.

Allergic reactions in tattoos are comparatively rare. In most cases the reactions are caused by different red pigments. While in the past these reactions have been ascribed to mercury salts (cinnebar) and cadmium sulphide, now synthetic inorganic azo dyes have also been found to be responsible for such reactions. A 42-year-old man presented with an allergic reaction in the red parts of his tattoos. Histologically a chronic granulomatous, partly fibrous inflammation with transfollicular elimination of pigment granules was found. Spontaneous regression in a part of the inflammatory reaction was observed, simultaneously with depigmentation and scarring of the overlying skin. The pigment used for tattooing was found to be an aromatic azo derivative. In addition to a positive cutaneous reaction to the dye, the patient also showed a positive patch test to Napthol AS, used for the coupling of different dyes in the textile industry.