Summary
Background
Contact allergy in children is becoming increasingly recognized as a cause of eczema. The causal agents may change with time, but there are few comparative data for this age group.
...Objectives
To compare data from the past 10 years with a similar study from the previous decade.
Methods
Between 2005 and 2014, 500 consecutive children who had been patch tested at Leeds Teaching Hospitals were identified, and the results were reviewed.
Results
Twenty‐seven per cent (134 cases) of children had one or more positive patch test findings. The mean ± standard deviation age of patients with a positive test reaction was 11.9 ± 4.1 years, which was significantly higher than that of patients with a negative result (10.9 ± 4.0 years) (p = 0.01; Mann–Whitney U‐test). No significant relationship between sex and a positive patch test result was found (p = 0.48, chi‐squared). Allergy to nickel was the most frequent finding, although this accounted for 18%, rather than 33% (1995–2004), of all positive reactions. The next most common allergens included fragrance mix 1 (17%), p‐phenylenediamine (16%), and methylchloroisothiazolinone/methylisothiazolinone (6%).
Conclusions
Although the overall incidence of contact allergy in our paediatric population is static, there has been a significant change in the allergens detected, probably as a result of changes in European legislation and cosmetic product use in children.
Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide ...(LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI.
In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated.
The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues.
Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.
p‐Phenylenediamine (PPD) (1,4‐diaminobenzene; CAS no. 106‐50‐3) is well known as key allergen in hair dye‐related allergic contact dermatitis. PPD can be N‐acetylated to the non‐sensitizing compounds ...mono‐PDD (MAPPD) and diacetyl‐PPD (DAPPD) by N‐acetyltransferase 1 (NAT1) in keratinocytes,1 and outside the skin also by N‐acetyltransferase 2 (NAT2).2 When investigating the elicitation response modification by NAT1 and NAT2 genotypes, we showed that genotypes containing the rapid acetylator allele NAT1*10 and individuals homozygous for the rapid acetylator allele NAT2*4 were under‐represented among PPD‐sensitized cases.3 Here, we evaluated this finding by investigating two well‐characterized highly sensitive cases with a longstanding history of allergic contact dermatitis caused by dyes.
Tribendimidine is a broad-spectrum anthelminthic available in China, which is currently being pursued for U.S. Food and Drug Administration approval for soil-transmitted helminth infections. ...Pharmacokinetic (PK) studies with tribendimidine in children, the main target group for treatment programs, have not been conducted to date. In the framework of a dose-ranging study in hookworm-infected school-aged children in Côte d'Ivoire, children were treated with either 100, 200, or 400 mg tribendimidine. Dried blood spot samples were collected up to 22 h after treatment. The active metabolite, deacetylated amidantel (dADT) and its metabolite acylated dADT (adADT) were quantified using liquid chromatography tandem mass spectrometry. PK parameters were calculated using a noncompartmental model, and univariate logistic regression was applied using maximal blood concentrations (
) and area under the blood concentration-time curve for 0 to 22 h (AUC
) as predictors of drug efficacy. Dried blood spot samples of 101 children were analyzed. We observed a less than proportional and proportional exposure in dADT's median
and AUC
, respectively, following administration of 100 mg (
= 853 ng/ml; AUC
= 3,019 h · ng/ml) and 400 mg (
= 2,275 ng/ml; AUC
= 12,530 h · ng/ml) tribendimidine. There were large, dose-independent variations in the time to
(
) and ratios of dADT to adADT. We did not detect an influence of
or AUC
of dADT or adADT on drug efficacy or adverse events. Since our study population was bearing hookworm infection of mainly low intensity, additional studies with heavy intensity infections might be required to confirm this observation.
Tire wear particles are not only the type of polymer particles most prevalent in the environment but also act as source of various organic micropollutants, many of which are likely still unknown. We ...extracted particles prepared from nine tires in artificial freshwater (28 d) with the goal to characterize leachables (max intensity >105 in artificial freshwater), which are tire-borne water contaminants. A subsequent extraction of these particles with acetone (3 h) was used to assess the long-term leaching potential. A suspect and nontarget screening in aliquots of each extract led to the detection of 214 organic substances of which 145 were classified as leachables. The intrinsic polarity of some leachables (mean log D (pH 7.4) 3.9), which facilitates an increased aquatic mobility, highlights their potential as environmental water contaminants. With N,N′-diphenylguanidine (DPG) and benzothiazole, two of the ten unequivocally identified leachables, are classified as potential persistent, mobile and toxic substance by the German Environment Agency. Of the identified chemicals DPG showed the highest intensities in aqueous extracts and N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6-PPD), the precursor of 6-PPD-quinone, in acetone extracts. A comparison between the 69 detected suspects and 174 high-intensity signals (>106) detected in the nontarget screening led to an overlap of only 29 features. A detailed investigation of the remaining high-intensity suspects revealed the presence of 13 proposed DPG reaction products, further highlighting the chemical complexity of tires. Consequently, we conclude that there are many, often still unrecognized chemicals entering the aquatic environment through leaching from tire wear particles.
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•214 organic substances were detected of which 145 were classified as leachables.•Ten features were identified unequivocally, for 58 a structure was proposed.•58% of leachables is within the polarity range expected for mobile chemicals.•45.8% of chemicals leaches less than 10% of their theoretical potential within 28 d.•13 potential reaction products of N,N′-diphenylguanidine were detected
N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) is a widely used additive for protecting various rubber products, and its product of oxidation ...N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPDQ) has attracted extensive attention in aquatic toxicity. However, the toxicity of 6PPD and 6PPDQ in mammals has not been reported yet. In this study, the effects of 6PPD and 6PPDQ on the liver of C57BL/6 mice were assessed by orally administering different doses of 6PPD and 6PPDQ (10, 30, and 100 mg/kg) in mice for 6 weeks. 6PPD and 6PPDQ were found to bioaccumulate in the liver in a dose-dependent manner. Moreover, a high dose of 6PPD and 6PPDQ exposure increased not only the liver weights but also liver triglyceride levels, indicating that 6PPD and 6PPDQ exposure induced hepatotoxicity in mice. Furthermore, transcriptomic analysis revealed that 6PPD and 6PPDQ induced differential expression of genes mainly enriched in glycolipid metabolism, immune-related, and glutathione metabolism pathways. Therefore, 6PPD and 6PPDQ altered hepatic metabolism in mice. Furthermore, 6PPDQ could induce an immune response by upregulating the transcription of immune-related genes and promoting macrophage infiltration in the liver. In conclusion, our study revealed the toxic effects of 6PPD and 6PPDQ exposure on multi-endpoints in the liver of mice and improve our understanding of the health risks of 6PPD and 6PPDQ to mammals. The findings of our study may help formulate better safety regulations for the use and disposal of rubber products.
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•6PPD and 6PPDQ could be bioaccumulated in liver of mice.•6PPD and 6PPDQ could induce lipid metabolism disorder in mice.•6PPD and 6PPDQ could lead to an inflammatory reaction.•6PPD and 6PPDQ could change different endpoints in the liver at biochemical and transcriptomic levels.
Visual detection of the methylglyoxal (MGO) level in the brain is critical for understanding its role in the onset and progression of AD. Herein, we disclosed a NIR fluorescent probe, DBTPP, for ...detecting MGO by utilizing a thiadiazole-fused o-phenylenediamine moiety as a MGO-specific sensing unit. DBTPP exhibits a series of distinct advantages, such as NIR emission, high selectivity and sensitivity, excellent acid-stability, and a huge off-on ratio. The probe could accurately monitor both exogenous and endogenous MGO variations in SH-SY5Y cells. Besides, it was able to image the endogenous MGO in a transgenic AD mouse model successfully, suggesting the great potential of MGO as a biomarker for early AD diagnosis.
Para-phenylenediamine (PPD) is one of the most used chemicals in oxidative hair dyes. However, its use has been associated with adverse effects on health, including contact dermatitis and other ...systemic toxicities. Novel PPD derivatives have been proposed as a safer replacement for PPD. This can be achieved if these molecules minimally permeate the skin and/or are easily metabolised by enzymes in the skin (e.g.,
N
-acetyltransferase-1 (NAT-1)) into innocuous compounds before gaining systemic entry. This study investigated the detoxification pathway mediated by NAT-1 enzymes on 6 synthesized PPD analogues (namely, P1–P6) with different chemical properties, to study the role of functional groups on detoxification mechanisms in HaCaT skin cells. These compounds were carefully designed with different chemical properties (whereby the
ortho
position of PPD was substituted by nucleophile and electrophile groups to promote
N
-acetylation reactions, metabolism and clearance). Compounds P2–P4
N
-acetylated at 54–49 nmol/mg/min, which is 1.6 times higher than
N
-acetylation of PPD, upregulated NAT-1 activity from 8–7% at 50 μM to 22–11% at 100 μM and showed 4 times higher rate of elimination (k equal to 0.141 ± 0.016–0.124 ± 0.01 h
−1
) and 3 times faster rate of clearance (0.172 ± 0.007–0.158 ± 0.005 h
−1
mgprotein
−1
) than PPD (0.0316 ± 0.0019 h
−1
, 0.0576 ± 0.003 h
−1
mg protein
−1
, respectively). The data suggest that nucleophile substituted compounds detoxify at a faster rate than PPD. Our metabolic and detoxification mechanistic studies revealed significantly higher rates of
N
-acetylation, NAT-1 activity and higher detoxification of P2–P4 in keratinocytes, suggesting the importance of nucleophilic groups at the
ortho
position in PPD to reduce toxicity of aniline-based dyes on human skin cells.
To assess the contamination and potential risk of snow melt with polar compounds, road and background snow was sampled during a melting event at 23 sites at the city of Leipzig and screened for 489 ...chemicals using liquid chromatography high-resolution mass spectrometry with target screening. Additionally, six 24 h composite samples were taken from the influent and effluent of the Leipzig wastewater treatment plant (WWTP) during the snow melt event. 207 compounds were at least detected once (concentrations between 0.80 ng/L and 75 μg/L). Consistent patterns of traffic-related compounds dominated the chemical profile (58 compounds in concentrations from 1.3 ng/L to 75 μg/L) and among them were 2-benzothiazole sulfonic acid and 1-cyclohexyl-3-phenylurea from tire wear and denatonium used as a bittern in vehicle fluids. Besides, the analysis unveiled the presence of the rubber additive 6-PPD and its transformation product N-(1.3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6-PPDQ) at concentrations known to cause acute toxicity in sensitive fish species. The analysis also detected 149 other compounds such as food additives, pharmaceuticals, and pesticides. Several biocides were identified as major risk contributors, with a more site-specific occurrence, to acute toxic risks to algae (five samples) and invertebrates (six samples). Ametryn, flumioxazin, and 1,2-cyclohexane dicarboxylic acid diisononyl ester are the main compounds contributing to toxic risk for algae, while etofenprox and bendiocarb are found as the main contributors for crustacean risk. Correlations between concentrations in the WWTP influent and flow rate allowed us to discriminate compounds with snow melt and urban runoff as major sources from other compounds with other dominant sources. Removal rates in the WWTP showed that some traffic-related compounds were largely eliminated (removal rate higher than 80%) during wastewater treatment and among them was 6-PPDQ, while others persisted in the WWTP.
To evaluate the efficacy and safety of ezogabine (United States adopted name)/retigabine (international nonproprietary name) (EZGRTG) 1,200 mg/day as adjunctive treatment in adults with ...drug-resistant epilepsy with partial-onset seizures with or without secondary generalization.
RESTORE 1 was a multicenter, randomized, double-blind, parallel-group trial. Following a prospective 8-week baseline phase, patients entered an 18-week double-blind treatment period (6-week forced dose titration to EZGRTG 1,200 mg/day in 3 equally divided doses or placebo, followed by a 12-week maintenance phase). Results were analyzed on an intent-to-treat basis for the entire 18-week period and for patients reaching the maintenance phase.
In 306 patients randomized, 305 received EZG(RTG) 1,200 mg/day (n = 153) or placebo (n = 152). Median percent reduction in total partial-seizure frequency was 44.3% vs 17.5% (p < 0.001) for EZG(RTG) and placebo, respectively, during the 18-week double-blind period; responder rates (≥50% reduction in total partial-seizure frequency from baseline) were 44.4% vs 17.8% (p < 0.001). In 256 patients (EZGRTG, 119; placebo, 137) entering the 12-week maintenance phase, median percent reduction in seizure frequency for EZG(RTG) vs placebo was 54.5% and 18.9% (p < 0.001), respectively; responder rates were 55.5% vs 22.6% (p < 0.001). The proportion of patients discontinuing due to treatment-emergent adverse events (TEAEs) was 26.8% (EZGRTG) vs 8.6% (placebo). Dizziness, somnolence, fatigue, confusion, dysarthria, urinary tract infection, ataxia, and blurred vision were the most common TEAEs reported by more patients treated with EZG(RTG) than placebo.
This study demonstrates that EZG(RTG) is effective as add-on therapy for reducing seizure frequency in patients with drug-resistant partial-onset seizures.
This study provides Class II evidence that EZG(RTG) 1,200 mg/day is effective as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.
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