Effects of slime toy poisoning in children and teenagers / Efeitos da intoxicação por slime em crianças e adolescentes

Abstract Objective: The aim of this study was to identify which types of skin reactions are associated with slime toys and which of their ingredients are most frequently involved in cases of poisoning. Data source: Between January and July 2021, articles were selected using PubMed, SciELO, and LILACS databases. The following descriptors were used: (dermatitis OR rash OR eczema OR inflammation) AND slime. Inclusion criteria were articles available in full, in either Portuguese, English, or Spanish, published between January 2000 and July 31, 2021, and articles reporting cases of contact dermatitis or eczema potentially or directly attributed to slime toys. Articles not meeting these criteria and duplicate texts in the databases were excluded. Data synthesis: In total, 65 publications were identified, of which 16 were included in this review. This resulted in a total of 22 children (2 males, 20 females), aged between 4 and 13 years, who were reportedly intoxicated by slime toys, most of these being linked to homemade preparations. Studies reported the occurrence of contact or allergic dermatitis on hands, fingers, nails, forearms, and cheeks. The most allergenic and/or irritant ingredients included liquid detergent and soap. Additionally, patch tests identified positive reactions to methylisothiazolinone and methylchloroisothiazolinone, the preservatives used by chemical industries on preparation of glue, soap, detergents, etc. Conclusions: Although slime toys might be important for improving motor development and parental relationships, homemade slime toy recipes include several allergenic and irritant ingredients which might be exposed to vulnerable children and cause intoxications. Therefore, homemade slime toys preparations should be used cautiously and under the supervision of adults.

Resumo Objetivo: Identificar quais tipos de reações de pele e ingredientes do brinquedo slime estão frequentemente envolvidos em relatos de intoxicação. Fontes de dados: Entre janeiro e julho de 2021, ocorreu a seleção dos artigos, utilizando-se as bases de dados: United States National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Foram utilizados os seguintes descritores: (dermatitis OR rash OR eczema OR inflammation) AND slime. Incluíram-se artigos disponíveis na íntegra, em português, inglês ou espanhol, publicados entre janeiro de 2000 e 31 julho de 2021, que relatassem casos de crianças e adolescentes que apresentaram reação cutânea após a manipulação do brinquedo slime. Foram excluídos artigos sem aderência ao tema e textos duplicados nas bases de dados. Síntese dos dados: Identificaram-se 65 publicações, sendo 16 utilizadas para a elaboração desta revisão. Isso resultou no total de 22 crianças (duas do sexo masculino, 20 do feminino), com idades entre quatro e 13 anos, que teriam sido intoxicadas por slime, a maioria dos casos ligado a preparações caseiras. Estudos relataram a ocorrência de dermatite de contato ou alérgica nas mãos, dedos, unhas, antebraços e bochechas. Os ingredientes mais alergênicos e/ou irritantes foram detergentes líquidos e sabão. Ademais, o patch test identificou reações positivas para metilisotiazolinona e metilcloroisotiazolinona, que são conservantes utilizados em produtos como cola, sabão, detergente, etc. Conclusões: Ainda que o brinquedo slime seja importante para o desenvolvimento motor e das relações parentais, receitas caseiras incluem vários ingredientes alergênicos e irritantes, que podem ser expostos a crianças vulneráveis e causar intoxicações. Sendo assim, as preparações do slime devem ser feitas com cautela e sob supervisão de adultos.

Pioglitazone Attenuates the Effects of Peripheral Inflammation in a Human In Vitro Blood-Brain Barrier Model.

Biological mediators secreted during peripheral chronic inflammation reach the bloodstream and may damage the blood-brain barrier (BBB), triggering central nervous system (CNS) disorders. Full-fledged human BBB models are efficient tools to investigate pharmacological pathways and mechanisms of injury at the BBB. We here employed a human in vitro BBB model to investigate the effects of either plasma from inflammatory bowel disease (IBD) patients or tumor necrosis factor α (TNFα), a cytokine commonly released in periphery during IBD, and the anti-inflammatory role of pioglitazone, a peroxisome proliferator-activated receptor γ agonist (PPARγ). The BBB model was treated with either 10% plasma from healthy and IBD donors or 5 ng/mL TNFα, following treatment with 10 µM pioglitazone. Patient plasma did not alter BBB parameters, but TNFα levels in plasma from all donors were associated with varying expression of claudin-5, claudin-3 and ICAM-1. TNFα treatment increased BBB permeability, claudin-5 disarrangement, VCAM-1 and ICAM-1 expression, MCP1 secretion and monocyte transmigration. These effects were attenuated by pioglitazone. Plasma from IBD patients, which evoked higher BBB permeability, also increased ICAM-1 expression, this effect being reversed by pioglitazone. Our findings evidence how pioglitazone controls periphery-elicited BBB inflammation and supports its repurposing for prevention/treating of such inflammatory conditions.

Effects of slime toy poisoning in children and teenagers.

OBJECTIVE: The aim of this study was to identify which types of skin reactions are associated with slime toys and which of their ingredients are most frequently involved in cases of poisoning. DATA SOURCE: Between January and July 2021, articles were selected using PubMed, SciELO, and LILACS databases. The following descriptors were used: (dermatitis OR rash OR eczema OR inflammation) AND slime. Inclusion criteria were articles available in full, in either Portuguese, English, or Spanish, published between January 2000 and July 31, 2021, and articles reporting cases of contact dermatitis or eczema potentially or directly attributed to slime toys. Articles not meeting these criteria and duplicate texts in the databases were excluded. DATA SYNTHESIS: In total, 65 publications were identified, of which 16 were included in this review. This resulted in a total of 22 children (2 males, 20 females), aged between 4 and 13 years, who were reportedly intoxicated by slime toys, most of these being linked to homemade preparations. Studies reported the occurrence of contact or allergic dermatitis on hands, fingers, nails, forearms, and cheeks. The most allergenic and/or irritant ingredients included liquid detergent and soap. Additionally, patch tests identified positive reactions to methylisothiazolinone and methylchloroisothiazolinone, the preservatives used by chemical industries on preparation of glue, soap, detergents, etc. CONCLUSIONS: Although slime toys might be important for improving motor development and parental relationships, homemade slime toy recipes include several allergenic and irritant ingredients which might be exposed to vulnerable children and cause intoxications. Therefore, homemade slime toys preparations should be used cautiously and under the supervision of adults.

Development of Annexin A1-surface-functionalized metal-complex multi-wall lipid core nanocapsules and effectiveness on experimental colitis.

Annexin A1 (AnxA1), a 37KDa protein, is secreted by inflammatory and epithelial cells and displays anti-inflammatory and wound healing activities in intestinal bowel diseases. Herein, we aimed to functionalize recombinant AnxA1 (AnxA1) on multi-wall lipid core nanocapsules (MLNC) and investigate its effectiveness on experimental colitis. MLNC were prepared by covering lipid core nanocapsules (LNC) with chitosan, which coordinates metals to specific protein chemisorption sites. Therefore, MLNC were linked to Zn2+ and AnxA1 was added to form MLNC-AnxA1. LNC, MLNC and MLNC-AnxA1 presented average size of 129, 152 and 163 nm, respectively, and similar polydispersity indexes (0.xx); incorporation of chitosan inverted the negative potential zeta; the coordination efficiency of AnxA1 was 92.22 %, and transmission electron microscope photomicrograph showed MLNC-AnxA1 had a spherical shape. The effectiveness of MLNC-AnxA1 was measured in Dextran Sulfate Sodium (DSS)-induced colitis in male C57BL/6 mice. DSS (2 % solution) was administered from days 1-6; saline, LNC, MLNC, MLNC-AnxA1 or AnxA1 were administered, once a day, by oral or intraperitoneal (i.p.) routes, from days 6-9. Clinical parameters of the disease were measured from day 0-10 and gut tissues were collected for histopathology, immunohistochemistry and flow cytometry analyses. Only i.p. treatment with MLNC-AnxA1 reduced weight loss, diarrhea and disease activity index, and prevented loss of colonic structure integrity; induced the switch of macrophages into M2 phenotype in the lamina propria; recovered the colonic histoarchitecture by decreasing dysplasia of crypts, inflammation and ulcerations; restored the expression of claudin-1 Zonna-occludens-1 tight junctions in the inflamed gut; and induced stem cell proliferation in intestinal crypts. Associated, data highlight the functionalization of MLNC with AnxA1 as a tool to improve the local actions of such protein in the inflamed gut by inducing resolution of inflammation and tissue repair.

Risk perception of automotive fuel poisoning among gas station attendants.

Introduction: Everyday, gas station attendants ate exposed to numerous toxic substances found in fuels. Benzene stands out among these toxic chemical agents; depending on its concentration, it can cause mucosal irritation or even pulmonary edema. A considerable number of gas station attendants is aware of the risks associated with benzene poisoning, but they are not aware of the risks associated with other automotive pollutants. Objectives: To evaluate and understand the risk perception of automotive fuel poisoning among gas station attendants in the Sorocaba region, state of São Paulo. Methods: Sixty gas station attendants were evaluated in the Sorocaba region. Data were collected between October 2019 and September 2020 using a semi-structured, individual, closed-ended questionnaire whose questions identified the participants' perception and aimed to analyze: the general profile of the studied population; practices for handling fuels and knowledge on their toxic effects, use and instructions of personal protective equipment, symptoms possibly associated with fuel exposure, the participants' perception of poisoning risks, and their participation in occupational medicine programs. Results: The obtained results demonstrated that most gas station attendants wore at least basic personal protective equipment, and some of them reported symptoms linked with benzene exposure. Still, a considerable number of employers does not provide adequate training to gas station attendants, which is possibly associated with inadequate use of personal protective equipment. Conclusions: Our data showed indications of non-compliance by gas station attendants as to the use of personal protective equipment at the workplace, and by employers as to the provision of adequate training.

Introdução: Todos os dias, trabalhadores frentistas são expostos a inúmeras substâncias tóxicas presentes nos combustíveis. Entre os agentes químicos tóxicos, destaca-se o benzeno que, dependendo da concentração, pode causar irritabilidade de mucosas e até edema pulmonar. Um número considerável de frentistas conhece os riscos associados à intoxicação por benzeno, porém desconhece os riscos causados pelos demais poluentes automotivos. Objetivos: Avaliar e compreender a percepção de risco de intoxicações por combustíveis automotivos em frentistas da região de Sorocaba, São Paulo. Métodos: Foram 60 frentistas avaliados na região de Sorocaba. A coleta de dados foi realizada de outubro de 2019 a setembro de 2020, a partir de um questionário semiestruturado, individual e fechado, cujas questões identificaram a percepção dos sujeitos envolvidos, buscando analisar: perfil geral da população estudada; práticas que envolvem o manuseio de combustíveis e o conhecimento sobre efeitos tóxicos; uso e instruções quanto aos equipamentos de proteção individual; sintomas possivelmente associados com exposição a combustíveis; percepção dos sujeitos quanto ao risco de intoxicações; participação em programas de medicina ocupacional. Resultados: Os resultados obtidos demonstraram que boa parte dos frentistas utiliza ao menos equipamentos de proteção individual básicos, e que alguns reportam sintomas ligados à exposição ao benzeno. Ainda, um número considerável de empregadores não fornece treinamento adequado aos frentistas, o que possivelmente se associa com uso inadequado de equipamentos de proteção individual. Conclusões: Os dados apresentados mostram que existe indícios de inobservância por parte dos frentistas quanto ao uso de equipamentos de proteção individual no local de trabalho e por parte de empregadores quanto à disponibilização de treinamento adequado.

Formyl Peptide Receptors and Annexin A1: Complementary Mechanisms to Infliximab in Murine Experimental Colitis and Crohn's Disease.

Non-responsiveness to anti-TNF-α therapies presents relevant rates in inflammatory bowel disease patients, presenting the need to find biomarkers involved in therapeutic efficacy. Herein, we demonstrate that higher levels of colonic formyl peptide receptor 1 and annexin A1 correlate with histological recovery in Crohn's disease patients under remission. Using the dextran sulfate sodium colitis model in mice, we suggest that infliximab induces annexin A1 expression and secretion in activated intestinal leukocytes. Conversely, this mechanism might stimulate epithelial formyl peptide receptors, inducing wound healing and consequent histological remission. Our data indicate that assessing intestinal expressions of formyl peptide receptors and annexin A1 might provide precious information on the disease activity and responsiveness to infliximab in inflammatory bowel disease patients.

Red light-emitting diode treatment improves tissue recovery in DSS-induced colitis in mice.

Inflammatory bowel diseases are debilitating illnesses characterized by severe inflammation of the gastrointestinal tract. Treatments currently available are expensive and ineffective. We here investigated the role of red-light emitting diode (LED) on dextran sodium sulfate (DSS)-induced colitis. DSS was added to the drinking water of male mice at days 0, 2, 4 and withdrawn at day 6. LED irradiation was performed daily for 90s from day 6 to 9 on the right and left sides of the ventral surface and beside the external anal region. LED treatment decreased the amount of crypt dysplasia/edema, inflammatory infiltrates and ulcers, attenuated apoptosis and increased proliferation of crypt cells. Also, LED treatment induced expression of annexin A1 in the damaged epithelium, preserved the organization of claudin-1 and skewed cytokine profiling towards a more anti-inflammatory status. Thus, LED treatment promotes structural protection and modulates the inflammatory response, constituting a potential non-invasive and low-cost combined therapy to help patients achieve disease remission.

Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages.

Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases (IBDs) which burden health systems worldwide; available pharmacological therapies are limited and cost-intensive. Use of peroxisome proliferator activated-receptor γ (PPARγ) ligands for IBD treatment, while promising, lacks solid evidences to ensure its efficacy. Annexin A1 (AnxA1), a glucocorticoid-modulated anti-inflammatory protein, plays a key role on IBD control and is a potential biomarker of IBD progression. We here investigated whether effects of pioglitazone, a PPARγ ligand, rely on AnxA1 actions to modulate IBD inflammation. Experimental colitis was evoked by 2% dextran sodium sulfate (DSS) in AnxA1 knockout (AnxA1-/-) or wild type (WT) C57BL/6 mice. Clinical and histological parameters were more severe for AnxA-/- than WT mice, and 10 mg/kg pioglitazone treatment attenuated disease parameters in WT mice only. AnxA1 expression was increased in tissue sections of diseased WT mice, correlating positively with presence of CD68+ macrophages. Metalloproteinase-9 (MMP-9) and inactive 33 kDa AnxA1 levels were increased in the colon of diseased WT mice, which were reduced by pioglitazone treatment. Cytokine secretion, reactive oxygen species generation and MMP-9 expression caused by lipopolysaccharide (LPS) treatment in AnxA1-expressing RAW 264.7 macrophages were reduced by pioglitazone treatment, effects not detected in AnxA1 knockdown macrophages. LPS-mediated increase of AnxA1 cleaving in RAW 264.7 macrophages was also attenuated by pioglitazone treatment. Finally, pioglitazone treatment increased extracellular signal-regulated kinase (ERK) phosphorylation in AnxA1-expressing RAW 264.7 macrophages, but not in AnxA1-knockdown macrophages. Thus, our data highlight AnxA1 as a crucial factor for the therapeutic actions of pioglitazone on IBDs.

Control of expression and activity of peroxisome proliferated-activated receptor γ by Annexin A1 on microglia during efferocytosis.

Annexin A1 (AnxA1) is a protein secreted by phagocytic cells which plays a pivotal role on the resolution of inflammation by enhancing phagocytosis carried out by phagocytes. Which factors and intracellular mechanisms are linked to such actions exerted by AnxA1 are yet to be completely understood. In order to investigate such, BV2 microglial cells were transfected with plasmids aimed at down-modulating AnxA1 expression and also treated with exogenous recombinant rAnxA1; gene and protein expression of proliferated-activated receptor γ (PPARγ) and CD36, STAT6 phosphorylation and phagocytosis of apoptotic neurons were investigated. Down-modulating AnxA1 in BV2 cells impaired gene and protein expression of PPARγ, effects reversed by treatment with recombinant AnxA1 (rAnxA1). Lower levels of CD36 were also verified in AnxA1 down-modulated BV2 cells. AnxA1-mediated phagocytosis of apoptotic cells was abrogated due to blockade of PPARγ activation, and in AnxA1 down-modulated cells exogenous AnxA1 failed to exert any effects on phagocytosis. Lower levels of STAT6/pSTAT6 in AnxA1 down-modulated BV2 cells suggest the involvement of this transcription factor with PPARγ and CD36 synthesis and actions. Data here shown suggest that there is a probable connection between AnxA1, PPARγ, and CD36, which must all act in association in order for efferocytosis to occur properly. AnxA1-mediated phosphorylation of STAT6 is probably involved with intracellular pathways involving PPARγ and CD36 actions. These data evidence that PPARγ/CD36 play a role on AnxA1-mediated efferocytosis in microglial cells. SIGNIFICANCE OF THE STUDY: The findings of this work provide evidence that the glucocorticoid-mediated protein annexin A1 modulates PPARγ expression and that PPARγ is important for annexin A1-mediated efferocytosis. Only recently the interaction between these two factors has begun to be explored, and knowledge on associated cell mechanisms are still scarce. Elucidating how annexin A1 and PPARγ interact with one another provides basis for further research aimed at understanding molecular pathways and cell signaling events involved with these factors, expanding existing knowledge on the anti-inflammatory effects of such factors.