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Occupational dermatoses impose a significant socioeconomic burden. Allergic contact dermatitis related to occupation is prevalent among healthcare workers, cleaning service personnel, individuals in the beauty industry and industrial workers. Among risk factors, the exposure to preservatives is frequent, since they are extensively added in products for occupational use. The goal of this study is to investigate the contact allergy patterns in order to understand the linkage among hypersensitivity to preservatives, occupational profiles, patients' clinical and demographic characteristics. Patch test results were collected from monosensitized patients to Formaldehyde 2%, KATHON 0.02%, thimerosal 0.1%, and MDBGN 0.5%; information was also collected for an extended MOAHLFA (Male-Occupational-Atopic-Hand-Leg-Face-Age) index. To assess the relationship between allergen group and occupational-related ACD, the chi-square test for independence was utilized. To uncover underlying relationships in the data, multiple correspondence analysis (MCA) and categorical principal components analysis (CATPCA), which are machine learning approaches, were applied. Significant relationships were found between allergen group and: occupation class, atopy, hand, leg, facial, trunk, neck, head dermatitis, clinical characteristics, ICDRG 48 h and ICDRG 72 h clinical evaluation. MCA and CATPCA findings revealed a link among allergen group, occupation class, patients' demographic and clinical characteristics, the MOAHLFA index, and the ICDRG scores. Significant relationships were identified between the allergen group and various manifestations of dermatitis. The utilization of machine learning techniques facilitated the discernment of meaningful patterns in the data. [ABSTRACT FROM AUTHOR]

Thimerosal (THI) has become a significant source of organic mercury pollutants in aquatic ecosystems, but there is limited information regarding its adverse effects on fish. In this study, zebrafish embryos were exposed to THI at 0 (control), 5.0, and 50 ng/L from 0–5 days post fertilization (dpf), and variations in their survival, development, behavior, free amino acid contents, and the biochemical responses involved in monoaminergic systems were examined. Although THI exposure did not significantly affect the survival, heart rate, or hatching time of zebrafish embryos, it substantially increased swimming velocity (136–154 % of the control) and reduced exploratory behavior (141–142 % of the control) in zebrafish larvae at 5 dpf. Exposure also significantly altered the amino acid contents (51–209 % of the control) and monoamine levels (70–154 % of the control) in zebrafish larvae, some of which displayed significant correlations with behavioral traits. THI significantly elevated dopamine receptor gene expression and monoamine oxidase activity in zebrafish larvae. Adding extra phenylalanine or tryptophan to the E3 medium facilitates the recovery of zebrafish larvae from the abnormal behaviors induced by THI. These findings reveal for the first time that THI exposure at the level of ng/L is sufficient to induce neurobehavioral toxic effects in the early life stages of zebrafish, and disrupting amino acid homeostasis is a critical underlying mechanism. This study provides valuable insights into the toxicity of THI to fish and highlights the importance of assessing its potential risks to aquatic ecosystems. [Display omitted] • Thimerosal (THI) at 5 and 50 ng/L has no lethal effects on the zebrafish embryos. • THI could induce hyperactivity and anxiety-related behavior in zebrafish larvae • THI disturbs amino acid contents and monoamine metabolism in zebrafish larvae • Behavioral variations associated with the contents of amino acids and monoamines • THI may alter behavior in zebrafish by disrupting their amino acid homeostasis [ABSTRACT FROM AUTHOR]

• Thimerosal (THI) reduced activity and anxiety in male zebrafish but not in females. • THI increased social interaction in males but decreased it in females. • THI decreased the 5-HT, 5-HIAA, DA, and DOPAC contents in the brain of males. • THI only decreased the DA contents in the brains of females. • THI may alter the behavioral traits of zebrafish by altering their brain monoamines. Thimerosal (THI) is the most widely used form of organic mercury in pharmaceutical and personal care products, and has become a major source of ethylmercury pollution in aquatic ecosystems. However, knowledge about its potential risk to aquatic species is limited. In this study, zebrafish were exposed to THI for 7 days, and variations in their behavioral traits, brain monoaminergic neurotransmitter contents, and related gene expression were investigated. After the 7-day exposure, THI reduced locomotor activity and thigmotaxis in males but not females. Exposure to THI increased the social interaction between females but decreased that between males. The THI exposure also significantly reduced the serotonin (5-HT), 5-hydroxyindoleacetic acid, dopamine (DA), and 3,4-dihydroxyphenylacetic acid contents in the brain of males, but only significantly decreased the DA content in females. Correlation analysis revealed that the neurochemical alterations in the brain of zebrafish play critical roles in the behavioral abnormalities induced by THI exposure. Moreover, THI also significantly altered the expression of some genes associated with the synthesis, metabolism, and receptor binding of 5-HT and DA in the brain of zebrafish. The differences in these gene expressions between female and male zebrafish exposed to THI seem to be an important mechanism underlying their sex-specific responses to this chemical. This is the first report on the sex-specific effects of THI on behaviors and brain monoaminergic neurotransmitter contents in zebrafish, which can further improve our understanding of its toxic effects on teleost. [ABSTRACT FROM AUTHOR]

• α7nAChRs pathway is crucial for the efficacy of citicoline in treating ASD in mice. • Citicoline increases the expressions and concentrations of brain α7nAChRs and Akt. • Citicoline increases brain content of Nrf2 and hippocampus contents of acetylcholine. • Citicoline decreases the brain levels of some oxidative stress markers. • Citicoline decreases the apoptotic marker and pro-inflammatory markers. Autism spectrum disorder (ASD) is a global concern, affecting around 75 million individuals. Various factors contribute to ASD, including mercury-containing preservatives like thimerosal (Thim) found in some vaccines. This study explored whether citicoline could be a therapeutic option for Thim-induced neuronal damage in a mouse model of ASD. Additionally, the study investigated the effects of citicoline on the α7nAChRs/Akt/Nrf2/caspase-3 pathway, which may be involved in the development of ASD. The study separated newborn mice into four groups. The control group received saline injections, while the Thim group received intramuscular injections of 3000 μg Hg/kg Thim on days 7, 9, 11, and 15 after birth. The two citicoline groups were administered Thim followed by intraperitoneal injections of 250 mg/kg or 500 mg/kg citicoline for three weeks. Afterward, various parameters were assessed, including growth, behavior, brain histopathology, oxidative stress, apoptotic, and inflammatory markers. Untreated Thim-exposed mice exhibited significant brain damage, which was substantially alleviated by citicoline treatment. This beneficial effect was associated with increased expressions and concentrations of brain α7nAChRs and Akt, increased brain content of Nrf2, and the hippocampus contents of acetylcholine. Citicoline treatment decreased the brain levels of oxidative stress markers (MDA and NO), the apoptotic marker caspase-3, and pro-inflammatory markers (NF-κB, TNF-α, and IL-1β). The drug also increased the brain GPx activity. Based on the results of this study, the α7nAChRs pathway appears to be essential for the therapeutic effectiveness of citicoline in treating Thim-induced ASD in mice. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common, aggressive, and fatal primary malignant brain tumor in adults. The therapeutic efficacy of temozolomide (TMZ) is limited owing to frequent treatment resistance. The latter is in part related to the overexpression of redox systems such as the thioredoxin system. This system is fundamental for cell survival and proliferation, regulating hypoxia inducible factor-1alpha (HIF-1α) activity, in turn controlling vascular endothelial growth factor (VEGF), which is indispensable for tumor invasiveness, angiogenesis and microenvironment maintenance. HIF-1α can also be regulated by the signal transducer and activator of transcription 3 (STAT3), an oncogene stimulated by pro-inflammatory cytokines and growth factors. The thioredoxin system has several known inhibitors including mercury compounds such as Thimerosal (TmHg) which readily crosses the blood-brain barrier (BBB) and accumulates in the brain. Though previously used in various applications epidemiological evidence on TmHg's neurotoxicity is lacking. The objective of this study was to verify whether thimerosal is a suitable candidate for hard repurposing to control glioblastoma; therefore, the effects of this molecule were evaluated in human GBM (U87) cells. Our novel results show that TmHg decreased cellular viability (>50%) and migration (up to 90% decrease in wound closure), reduced thioredoxin reductase (TrxR/TXNRD1) and thioredoxin (Trx) activity, and increased reactive oxygen species (ROS) generation. Moreover, TmHg reduced HIF-1α expression (35%) as observed by immunofluorescence. Co-exposure of U87 cells to TmHg and TMZ reduced HIF-1α, VEGF, and phosphorylated STAT3. Consequently, TmHg alone or combined with chemotherapeutic drugs can reduce neoangiogenesis and ameliorate glioblastoma progression and treatment. [Display omitted] • Thioredoxin system inhibition by thimerosal increases ROS and cancer cell death; • Thimerosal strongly affects glioblastoma (U87) cells viability and migration; • Thimerosal hinders HIF-1α expression and angiogenesis signaling pathways; • Co-exposure of U87 cells to thimerosal and temozolamide reduces HIF-1α, VEGF, and pSTAT3; • Thimerosal kills human resistant glioblastoma cells and reduces treatment resistance. [ABSTRACT FROM AUTHOR]

Introduction: Potentially harmful excipients (PHEs) for children have been reported and the need for information collection has been advocated. However, studies on the actual occurrence of adverse events are limited. This study investigated the quantitative exposure of PHEs via injection and their association with adverse events in children under 2 years of age., Materials and Methods: As a single-center observational study, children aged 0-23 months received injectable drugs from April 1, 2018, to March 31, 2023 were included. Information on PHE exposure and adverse events after administration were extracted from medical records. Sodium benzoate, benzyl alcohol, ethanol, glycerol, lactose, polyethylene glycol paraben, polysorbate, propylene glycol, sorbitol, sucrose, sulfite, and thimerosal were selected as PHEs., Results and Discussion: 6265 cases, 333,694 prescriptions, and 368 drugs (264 ingredients) were analyzed. The median age was 0.63 years (interquartile range [IQR] 0.1-1.1). 72,133 prescriptions, 132 drugs and 99 ingredients contained PHE; 2,961 cases exposed to PHE and 1825 cases exceeding permitted daily exposure. The drug with the highest number of exposure cases was hydroxyzine, and the highest number of prescriptions was heparin (both drugs contain benzyl alcohol). In association between adverse events and PHE exposure, higher doses in cases of adverse event occurrence were found in benzyl alcohol, glycerol, polyethylene glycol, and polysorbate exposed cases. Among thimerosal-exposed cases, "developmental delay" was more frequent in exposed cases, but the causal relationship was unknown. Further investigation is needed to clarify the relationship between adverse events and PHE exposure. Additionally, more precise information on PDE for pediatrics including neonates is necessary., (© 2023. The Author(s), under exclusive licence to The Drug Information Association, Inc.)