Coupling Different Road Traffic Noise Models with a Multilinear Regressive Model: A Measurements-Independent Technique for Urban Road Traffic Noise Prediction.

Road traffic noise is a severe environmental hazard, to which a growing number of dwellers are exposed in urban areas. The possibility to accurately assess traffic noise levels in a given area is thus, nowadays, quite important and, on many occasions, compelled by law. Such a procedure can be performed by measurements or by applying predictive Road Traffic Noise Models (RTNMs). Although the first approach is generally preferred, on-field measurement cannot always be easily conducted. RTNMs, on the contrary, use input information (amount of passing vehicles, category, speed, among others), usually collected by sensors, to provide an estimation of noise levels in a specific area. Several RTNMs have been implemented by different national institutions, adapting them to the local traffic conditions. However, the employment of RTNMs proves challenging due to both the lack of input data and the inherent complexity of the models (often composed of a Noise Emission Model-NEM and a sound propagation model). Therefore, this work aims to propose a methodology that allows an easy application of RTNMs, despite the availability of measured data for calibration. Four different NEMs were coupled with a sound propagation model, allowing the computation of equivalent continuous sound pressure levels on a dataset (composed of traffic flows, speeds, and source-receiver distance) randomly generated. Then, a Multilinear Regressive technique was applied to obtain manageable formulas for the models' application. The goodness of the procedure was evaluated on a set of long-term traffic and noise data collected in a French site through several sensors, such as sound level meters, car counters, and speed detectors. Results show that the estimations provided by formulas coming from the Multilinear Regressions are quite close to field measurements (MAE between 1.60 and 2.64 dB(A)), confirming that the resulting models could be employed to forecast noise levels by integrating them into a network of traffic sensors.

The interplay between environmental exposures and COVID-19 risks in the health of children.

BACKGROUND: An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. OBJECTIVES: To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. METHODS: An international group of researchers interested in children's environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. DISCUSSION: Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a "dirty" environment in conveying protection - an example of the "hygiene hypothesis"; and what are the long term health effects of SARS-Cov-2 infection in early life. CONCLUSION: A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.

The actin-binding protein profilin 2 is a novel regulator of iron homeostasis.

Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis-regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA). We identified profilin 2 (Pfn2) mRNA, which encodes an actin-binding protein involved in endocytosis and neurotransmitter release, as a novel IRP-interacting transcript, and studied its role in iron metabolism. A combination of electrophoretic mobility shift assay experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3' untranslated region of Pfn2 mRNA. Pfn2 mRNA levels were significantly reduced in duodenal samples from mice with intestinal IRP ablation, suggesting that IRPs exert a positive effect on Pfn2 mRNA expression in vivo. Overexpression of Pfn2 in HeLa and Hepa1-6 cells reduced their metabolically active iron pool. Importantly, Pfn2-deficient mice showed iron accumulation in discrete areas of the brain (olfactory bulb, hippocampus, and midbrain) and reduction of the hepatic iron store without anemia. Despite low liver iron levels, hepatic hepcidin expression remained high, likely because of compensatory activation of hepcidin by mild inflammation. Splenic ferroportin was increased probably to sustain hematopoiesis. Overall, our results indicate that Pfn2 expression is controlled by the IRPs in vivo and that Pfn2 contributes to maintaining iron homeostasis in cell lines and mice.

Cysteine Prevents the Reduction in Keratin Synthesis Induced by Iron Deficiency in Human Keratinocytes.

L-cysteine is currently recognized as a conditionally essential sulphur amino acid. Besides contributing to many biological pathways, cysteine is a key component of the keratin protein by its ability to form disulfide bridges that confer strength and rigidity to the protein. In addition to cysteine, iron represents another critical factor in regulating keratins expression in epidermal tissues, as well as in hair follicle growth and maturation. By focusing on human keratinocytes, the aim of this study was to evaluate the effect of cysteine supplementation as nutraceutical on keratin biosynthesis, as well as to get an insight on the interplay of cysteine availability and cellular iron status in regulating keratins expression in vitro. Herein we demonstrate that cysteine promotes a significant up-regulation of keratins expression as a result of de novo protein synthesis, while the lack of iron impairs keratin expression. Interestingly, cysteine supplementation counteracts the adverse effect of iron deficiency on cellular keratin expression. This effect was likely mediated by the up-regulation of transferrin receptor and ferritin, the main cellular proteins involved in iron homeostasis, at last affecting the labile iron pool. In this manner, cysteine may also enhance the metabolic iron availability for DNA synthesis without creating a detrimental condition of iron overload. To the best of our knowledge, this is one of the first study in an in vitro keratinocyte model providing evidence that cysteine and iron cooperate for keratins expression, indicative of their central role in maintaining healthy epithelia.

2,3,7,8-Tetrachlorodibenzo-p-dioxin impairs iron homeostasis by modulating iron-related proteins expression and increasing the labile iron pool in mammalian cells.

Cellular iron metabolism is essentially controlled by the binding of cytosolic iron regulatory proteins (IRP1 or IRP2) to iron-responsive elements (IREs) located on mRNAs coding for proteins involved in iron acquisition, utilization and storage. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent toxins of current interest that occurs as poisonous chemical in the environment. TCDD exposure has been reported to induce a broad spectrum of toxic and biological responses, including significant changes in gene expression for heme and iron metabolism associated with liver injury. Here, we have investigated the molecular effects of TCDD on the iron metabolism providing the first evidence that administration of the toxin TCDD to mammalian cells affects the maintenance of iron homeostasis. We found that exposure of Madin-Darby Bovine Kidney cell to TCDD caused a divergent modulation of IRP1 and IRP2 RNA-binding capacity. Interestingly, we observed a concomitant IRP1 down-regulation and IRP2 up-regulation thus determining a marked enhancement of transferrin receptor 1 (TfR-1) expression and a biphasic response in ferritin content. The changed ferritin content coupled to TfR-1 induction after TCDD exposure impairs the cellular iron homeostasis, ultimately leading to significant changes in the labile iron pool (LIP) extent. Since important iron requirement changes occur during the regulation of cell growth, it is not surprising that the dioxin-dependent iron metabolism dysregulation herein described may be linked to cell-fate decision, supporting the hypothesis of a central connection among exposure to dioxins and the regulation of critical cellular processes. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Design, synthesis and characterisation of guanosine-based amphiphiles.

A small library of sugar-modified guanosine derivatives has been prepared, starting from a common intermediate, fully protected on the nucleobase. Insertion of myristoyl chains and of diverse hydrophilic groups, such as an oligoethylene glycol, an amino acid or a disaccharide chain, connected through in vivo reversible ester linkages, or of a charged functional group provided different examples of amphiphilic guanosine analogues, named G1-G7 herein. All of the sugar-modified derivatives were positive in the potassium picrate test, showing an ability to form G-tetrads. CD spectra demonstrated that, as dilute solutions in CHCl(3), distinctive G-quadruplex systems may be formed, with spatial organisations dependent upon the structural modifications. Two compounds, G1 and G2, proved to be good low-molecular-weight organogelators in polar organic solvents, such as methanol, ethanol and acetonitrile. Ion transportation experiments through phospholipid bilayers were carried out to evaluate their ability to mediate H(+) transportation, with G5 showing the highest activity within the investigated series. Moreover, G3 and G5 exhibited a significant cytotoxic profile against human MCF-7 cancer cells in in vitro bioassays.

[Cocaine base paste: experience from the Montevideo Poison Control Center]. / Pasta base de cocaína: experiencia del Centro de Información y Asesoramiento Toxicológico.

BACKGROUND: In Uruguay, cocaine base paste (CBP, pasta base) is a widely used form of cocaine. The aim of our study is to determine the main clinical characteristics of CBP abusers. METHODS: Retrospective, single-center study of consultations at the Montevideo Poison Control Center between January 1, 2004 and December 31, 2005. RESULTS: One hundred and thirteen consultations were included, with an average age of 22 years (+ - 0.5 years) and a female-male sex ratio of 1:4.3. The consultations were related to drug overdose (77%), suicide attempt (16.8%), and wanting to give up CBP use (6.2%). In 48.1% the time elapsed since inhalation of CBP was less than 6 hours. Doses varied between 0.5 gr. and 25 gr. Use of other drugs at the same time, such as alcohol, marijuana or benzodiazepines, was common (51 cases). The symptoms most frequently observed were neuropsychiatric and cardiovascular, followed by respiratory symptoms. In 16.8% of patients, reason for the consultation was intentional acute ingestion of drugs, considered as a suicide attempt, occurring within a few hours of drug consumption. DISCUSSION: CBP users are mostly young males. Although clinical findings are compatible with those for cocaine abuse, euphoria is a major clinical feature in CBP abusers. The presence of respiratory symptoms reflects the complications associated with the ingestion route. Suicide attempts occurring within a few hours of CBP confirm the high prevalence of suicidal ideation reported by other authors. cocaine base paste, clinical features, suicide attempts.

Impact of pesticide exposure in childhood.

Pesticides represent a wide variety of chemicals presented as different formulations and concentrations and used in different settings: agriculture, animal sanitary bath, domestic use, and vector control. Lack of awareness, poor agricultural practices, and inappropriate disposal of containers will increase the exposure and risk of health effects during childhood. The concern about children's exposure to pesticides is based on their toxic properties and the special vulnerability to the exposure, which may occur in different stages, from the prenatal period to infancy. Pesticide related diseases may manifest during the infancy, adolescence, or adulthood. Children may be exposed by multiple routes of exposure, in different scenarios. In domestic settings, insecticides and rodenticides are usually stored within the reach of children, or may be transferred to non-original containers, leading to acute non intentional ingestion. Exploratory behavior increases the risk for exposure to pesticides present on the ground. Gardens and playgrounds may have pesticides residues. Children may be in contact with domestic animals that have been treated with pesticides. In rural settings, children can be exposed to pesticide residues in areas where they have been applied, or by contamination of work equipment and parents clothing. Families dedicated to rural activity have higher levels of exposure, through ingesting contaminated fruits, vegetables, milk, eggs, and water. Several studies confirmed pesticide exposure in children by biomonitoring. Higher levels of organophosphate metabolites have been reported in children compared to adult populations. Toxic effects of pesticides depend on their intrinsic toxic properties as well as on the dose, duration, and life period of exposure. Acute poisonings are related to high doses exposure, while chronic, subtle and delayed effects are often related to low levels/doses exposure. Epidemiologic, animal, and clinical studies suggest an association between chronic, low-level exposures and alterations in growth and development (particularly impaired neurobehavioral development), cancer and increased susceptibility to infections. New research presents evidence that some pesticides are a risk factor of a wide range of acute and chronic diseases. Better practices and public health policies are needed to prevent and protect children from pesticides exposure.

Severe dioxin-like compound (DLC) contamination in e-waste recycling areas: An under-recognized threat to local health.

Electrical and electronic waste (e-waste) burning and recycling activities have become one of the main emission sources of dioxin-like compounds (DLCs). Workers involved in e-waste recycling operations and residents living near e-waste recycling sites (EWRS) are exposed to high levels of DLCs. Epidemiological and experimental in vivo studies have reported a range of interconnected responses in multiple systems with DLC exposure. However, due to the compositional complexity of DLCs and difficulties in assessing mixture effects of the complex mixture of e-waste-related contaminants, there are few studies concerning human health outcomes related to DLC exposure at informal EWRS. In this paper, we have reviewed the environmental levels and body burdens of DLCs at EWRS and compared them with the levels reported to be associated with observable adverse effects to assess the health risks of DLC exposure at EWRS. In general, DLC concentrations at EWRS of many countries have been decreasing in recent years due to stricter regulations on e-waste recycling activities, but the contamination status is still severe. Comparison with available data from industrial sites and well-known highly DLC contaminated areas shows that high levels of DLCs derived from crude e-waste recycling processes lead to elevated body burdens. The DLC levels in human blood and breast milk at EWRS are higher than those reported in some epidemiological studies that are related to various health impacts. The estimated total daily intakes of DLCs for people in EWRS far exceed the WHO recommended total daily intake limit. It can be inferred that people living in EWRS with high DLC contamination have higher health risks. Therefore, more well-designed epidemiological studies are urgently needed to focus on the health effects of DLC pollution in EWRS. Continuous monitoring of the temporal trends of DLC levels in EWRS after actions is of highest importance.

Prevention-intervention strategies to reduce exposure to e-waste.

As one of the largest waste streams, electronic waste (e-waste) production continues to grow in response to global demand for consumer electronics. This waste is often shipped to developing countries where it is disassembled and recycled. In many cases, e-waste recycling activities are conducted in informal settings with very few controls or protections in place for workers. These activities involve exposure to hazardous substances such as cadmium, lead, and brominated flame retardants and are frequently performed by women and children. Although recycling practices and exposures vary by scale and geographic region, we present case studies of e-waste recycling scenarios and intervention approaches to reduce or prevent exposures to the hazardous substances in e-waste that may be broadly applicable to diverse situations. Drawing on parallels identified in these cases, we discuss the future prevention and intervention strategies that recognize the difficult economic realities of informal e-waste recycling.

E-Waste Informal Recycling: An Emerging Source of Lead Exposure in South America.

BACKGROUND: Primitive electronic waste (e-waste) recycling creates exposures to several hazardous substances including lead. In Uruguay, primitive recycling procedures are a significant source of lead exposure. OBJECTIVES: The aim of this study was to examine lead exposure in blood lead levels (BLLs) in low-income children exposed to lead through burning cables. METHODS: A sample of children and adolescents exposed to lead through burning cable activities were assessed at the Department of Toxicology in Montevideo, Uruguay, between 2010 and 2014. Soil lead levels of residences were taken shortly after their assessment. FINDINGS: The final sample included 69 children and adolescents (mean age 7.89 years). More than 66% of participants had an additional source of lead exposure-manual gathering of metals-and <5% were exposed to lead through landfills or paint. Average BLLs at first consultation were 9.19 ug/dL and lower at the second measurement (5.86 µg/dL). Data from soil lead levels ranged from 650 to 19,000 mg of lead/kg of soil. The interventions conducted after the assessment included family education in the clinic and at home, indoor and outdoor remediation. We found a decrease in BLLs of 6.96 µg/dL. Older children had lower BLLs (r = -0.24; P = 0.05). Statistical analyses also showed that children living in areas with higher soil lead levels had significantly higher BLLs (r = 0.50; P < 0.01). Additionally, we found greater BLLs from burning cable activities when children had been exposed to lead-based paint (r = 0.23; P < 0.1). CONCLUSION: Among children exposed to e-waste recycling, the most common additional source of lead exposure was the manual gathering of metals. The average BLL among children and adolescents in this study is higher than the BLLs currently suggested in medical intervention. Future research should focus on exploring effective interventions to reduce lead exposure among this vulnerable group.

E-Waste and Harm to Vulnerable Populations: A Growing Global Problem.

BACKGROUND: Electronic waste (e-waste) is produced in staggering quantities, estimated globally to be 41.8 million tonnes in 2014. Informal e-waste recycling is a source of much-needed income in many low- to middle-income countries. However, its handling and disposal in underdeveloped countries is often unsafe and leads to contaminated environments. Rudimentary and uncontrolled processing methods often result in substantial harmful chemical exposures among vulnerable populations, including women and children. E-waste hazards have not yet received the attention they deserve in research and public health agendas. OBJECTIVES: We provide an overview of the scale and health risks. We review international efforts concerned with environmental hazards, especially affecting children, as a preface to presenting next steps in addressing health issues stemming from the global e-waste problem. DISCUSSION: The e-waste problem has been building for decades. Increased observation of adverse health effects from e-waste sites calls for protecting human health and the environment from e-waste contamination. Even if e-waste exposure intervention and prevention efforts are implemented, legacy contamination will remain, necessitating increased awareness of e-waste as a major environmental health threat. CONCLUSION: Global, national, and local levels efforts must aim to create safe recycling operations that consider broad security issues for people who rely on e-waste processing for survival. Paramount to these efforts is reducing pregnant women and children's e-waste exposures to mitigate harmful health effects. With human environmental health in mind, novel dismantling methods and remediation technologies and intervention practices are needed to protect communities. CITATION: Heacock M, Kelly CB, Asante KA, Birnbaum LS, Bergman AL, Bruné MN, Buka I, Carpenter DO, Chen A, Huo X, Kamel M, Landrigan PJ, Magalini F, Diaz-Barriga F, Neira M, Omar M, Pascale A, Ruchirawat M, Sly L, Sly PD, Van den Berg M, Suk WA. 2016. E-waste and harm to vulnerable populations: a growing global problem. Environ Health Perspect 124:550-555; http://dx.doi.org/10.1289/ehp.1509699.

Intoxicación aguda no intencional grave con alcohol isopropílico en el Departamento de Emergencia Pediátrica del Centro Hospitalario Pereira Rossell. A propósito de tres casos clínicos / Acute unintentional poisoning with isopropyl alcohol in the Pereira Rossell Pediatric Emergency Ward. Three clinical cases / Intoxicação aguda não intencional com álcool isopropílico na Emergência Pediátrica do Centro Hospitalar Pereira Rossell. Três relatos de caso

Resumen: Las intoxicaciones agudas en los servicios de emergencia pediátrica ocupan un lugar importante dentro de la patología pediátrica de urgencia por su potencial riesgo vital. El Centro de Información y Asesoramiento Toxicológico (CIAT) recibe anualmente un promedio de 10.000 consultas, el 45% corresponde a la edad pediátrica. La intoxicación aguda por isopropanol es poco frecuente, pero potencialmente grave. El CIAT ha registrado 34 casos en los últimos cinco años. El alcohol isopropílico se encuentra en muchos productos de limpieza y desinfectantes. La intoxicación aguda se caracteriza inicialmente por síntomas digestivos. En la evolución pueden agregarse manifestaciones neurológicas: depresión de conciencia, hipotonía e hiporreflexia, asociada a hipoglicemia, gap osmolar elevado, cetonemia y cetonuria. En casos graves puede ocasionar hipotermia, hipotensión y arritmias. La acidosis metabólica es poco frecuente, a diferencia de otros alcoholes. En este caso, la toxicidad aguda es dependiente en gran medida de la formación de metabolitos. En este trabajo son isopropanol y acetona los responsables de las manifestaciones clínicas y alteraciones en los estudios de laboratorio. Se analizaron tres casos clínicos en niños de 96, 18 y 15 meses. Los tres casos evolucionaron de forma favorable en 72-96 horas, y, como se refiere en la literatura, el pronóstico en general es bueno y sin secuelas. El abordaje de estos pacientes en la urgencia se basa en la aplicación del triángulo de evaluación pediátrica y la secuencia A, B, C, D, E con el propósito de identificar en forma precoz la necesidad de realizar correcciones metabólicas o soporte de funciones.

Summary: Acute poisoning in pediatric emergency services is an important part of the emergency pediatric pathology due to its potential risk. CIAT receives an average of 10,000 consultations annually, 45% of which are from children. Acute isopropanol poisoning is rare but potentially serious. CIAT has recorded 34 cases in the last 5 years. Isopropyl alcohol is found in many cleaning products and disinfectants. Acute poisoning is initially characterized by digestive symptoms. Some neurological manifestations may arise during the acute poisoning evolution, such as, depression of consciousness, hypotonia and hyporeflexia, associated with hypoglycemia, elevated osmolar gap, ketonemia and ketoneuria. In severe cases, it can cause hypothermia, hypotension and arrhythmia. Metabolic acidosis is rare, unlike what happens with other alcohols. In this case, acute toxicity largely depends on the formation of metabolites; in this case, isopropanol and acetone are responsible for clinical manifestations and alterations in laboratory studies. We hereby present three clinical cases of children aged 96, 18 and 15 months. The three cases evolved favorably in 72-96 hours and, as described in the literature, the prognosis in general is good and without sequelae. The approach to these patients in the emergency ward was the pediatric evaluation triangle and the A, B, C, D, E sequence in order to identify early the need to perform metabolic corrections and / or support functions.

Resumo: As intoxicações agudas nos serviços de emergência pediátrica ocupam um lugar importante na patologia pediátrica de emergência devido ao seu risco potencial para a vida. O CIAT recebe, em média, 10.000 consultas anualmente, 45% de pacientes pediátricos. A intoxicação aguda por isopropanol é rara, mas potencialmente grave. O CIAT registrou 34 casos nos últimos 5 anos. O álcool isopropílico encontra-se em vários produtos de limpeza e desinfetantes. O envenenamento agudo é inicialmente caracterizado por sintomas digestivos. Na evolução do envenamento, podem aparecer manifestações neurológicas: depressão da consciência, hipotonia e hiporreflexia, associadas à hipoglicemia, gap osmolar elevado, cetonemia e cetoneúria. Em casos graves, pode causar hipotermia, hipotensão e arritmias. A acidose metabólica é rara, diferentemente do que acontece com outros álcoois. Nesse caso, a toxicidade aguda depende em grande parte da formação de metabólitos; neste caso, isopropanol e acetona são responsáveis pelas manifestações clínicas e alterações em estudos laboratoriais. Analisaram-se três casos clínicos em crianças de 96, 18 e 15 meses. Os três casos evoluíram favoravelmente em 72-96 horas e, como relatamos na literatura, o prognóstico em geral é bom e sem sequelas. A abordagem desses pacientes na emergência foi a aplicação do triângulo de avaliação pediátrica na sequência A, B, C, D, E, a fim de identificar precocemente a necessidade de realizar correções metabólicas e / ou suporte de funções.

Isquemia miocárdica por consumo de dibutilona / Myocardial ischemia from dibutylone use / Isquemia miocárdica por uso de dibutilona

Resumen: Las catinonas sintéticas son drogas estimulantes de síntesis, comercializadas en el mercado ilegal por sus propiedades estimulantes y perturbadoras del sistema nervioso central, para su uso recreativo, solas, o como adulterantes de cocaína y derivados anfetamínicos. A nivel mundial existe un número creciente de reportes de intoxicaciones agudas y complicaciones por consumo de estas sustancias. En Uruguay fueron detectadas por primera vez en el año 2015, existiendo una información epidemiológica muy limitada. Las catinonas sintéticas no se detectan por las técnicas inmunocromatográficas disponibles en los laboratorios de los servicios de urgencias de nuestro país. Se describe el primer caso de intoxicación por una catinona sintética (dibutilona) en Uruguay, en un paciente de 45 años, por consumo de un polvo vendido como "éxtasis", presentando como complicación un síndrome coronario agudo, con una buena evolución posterior. La confirmación diagnóstica se realizó mediante su detección en orina por cromatografía de gases acoplada a espectrometría de masas. La estructura química de la dibutilona y su mecanismo de acción explican las manifestaciones clínicas y la complicación isquémica por vasoespasmo coronario. En ausencia de una noción clara de exposición y ante la situación epidemiológica actual, la presencia de un cuadro clínico compatible con una droga estimulante y resultado negativo para cocaína y anfetaminas en estudios inmunocromatográficos, debe hacer plantear la sospecha de otros estimulantes de síntesis como las catinonas, tal como ocurrió en este caso.

Summary: Synthetic cathinone are stimulating synthetic drugs used for recreational purposes on their own or as adulterants in cocaine and amphetamines derivatives that are traded in illegal markets given their stimulating and disturbing properties on the central nervous system. Globally, there is a growing number of acute intoxications and complications as a consequence of consumption of these substances. In Uruguay they were first detected in 2015, there being limited epidemiological data. Synthetic cathinone are not detected by the immunochromatographic tests available at the laboratories of the emergency services in our country. The study describes the first case of intoxication by a synthetic cathinone (dibutylone) in Uruugay, in a 45 year old patient as a result of powder sold as "ecstasy". The patient presented an acute coronary syndrome, subsequent evolution being good. Diagnostic confirmation was made in urine using gas chromatography coupled with mass spectrometry. The chemical structure of dibutylone and its action mechanism explain the clinical manifestations and the coronary vasospasm causing ischemia. When there is no clear sign of a patient having been exposed to this substance and upon the current epidemiological state, the presence of clinical symptoms that are compatible with a stimulating drug and a negative result for cocaine and amphetamines in immunochromatographic tests must lead us to be suspicious about the presence of synthetic stimulating substances as cathinone, as in the case studied.

Resumo: Catinonas sintéticas são drogas estimulantes sintéticas, comercializadas no mercado ilegal por suas propriedades estimulantes e perturbadoras do sistema nervoso central, para uso recreativo isoladamente ou como adulterantes da cocaína e derivados de anfetaminas. Em todo o mundo cresce o número de relatos de intoxicações agudas e complicações decorrentes do uso dessas substâncias. No Uruguai, foram detectados pela primeira vez em 2015 com informações epidemiológicas muito limitadas. As catinonas sintéticas não são detectadas pelas técnicas imunocromatográficas disponíveis nos laboratórios de pronto-socorro de nosso país. Descreve-se o primeiro caso de intoxicação por catinona sintética (dibutilona) em nosso país, em um paciente de 45 anos, devido ao consumo de um pó vendido como "ecstasy", apresentando como complicação uma síndrome coronariana aguda, com boa evolução posterior. A confirmação diagnóstica foi feita por sua detecção na urina por cromatografia gasosa acoplada à espectrometria de massa. A estrutura química da dibutilona e seu mecanismo de ação explicam as manifestações clínicas e complicações isquêmicas devido ao vasoespasmo coronariano. Na ausência de uma noção clara de exposição e dada a situação epidemiológica atual, a presença de quadro clínico compatível com droga estimulante e resultado negativo para cocaína e anfetaminas em estudos imunocromatográficos, deve levantar a suspeita de outros estimulantes sintéticos como as catinonas, como aconteceu neste caso.

Efectos del consumo de cannabis durante el embarazo y la lactancia / Effects of cannabis consumption during pregnancy and lactation / Efeitos do consumo de cannabis durante a gravidez e a amamentação

Resumen: La marihuana se consume en menor proporción que el alcohol y el tabaco. La edad de mayor frecuencia de consumo coincide con la edad reproductiva. Los cannabinoides tienen características cinéticas y mecanismos de acción que suponen riesgo de exposición fetal y en la lactancia. El embarazo presenta cambios fisiológicos que facilitan la exposición fetal. La vulnerabilidad del sistema endocanabinoide en la etapa de desarrollo neurológico plantea la sospecha de efectos adversos asociados a la exposición a cannabis y derivados. Este trabajo tiene como objetivo actualizar la información científica sobre los efectos del consumo de cannabis y derivados durante el embarazo y la lactancia. Se realizó una revisión descriptiva de artículos publicados en revistas científicas arbitradas entre enero de 2010 y diciembre de 2018. Se incluyó el análisis de bases de datos utilizando combinaciones de términos en idioma inglés y español: "marihuana", "cannabis", "cannabinoides", "embarazo", "lactancia". Los efectos asociados con el consumo de marihuana en el embarazo no son concluyentes, aunque hay creciente evidencia de su asociación con alteraciones en el nacimiento, como bajo peso al nacer y daños en el neurodesarrollo que impactan en el niño y se mantienen en la infancia tardía y la adolescencia. No se encontró asociación con otros indicadores como mortalidad perinatal y prematurez. Entre las debilidades de los estudios revisados, la mayoría están basados en el autorreporte y plantean dificultades e incertidumbres respecto al consumo de otras sustancias como factor de confusión. Hasta el momento la evidencia es suficiente para adoptar el principio de precaución y recomendación de evitar su consumo durante el embarazo y la lactancia.

Summary: Marijuana consumption is lower than that of alcohol and tobacco. The highest consumption frequency takes place during reproductive age. Cannabinoids have kinetic characteristics and action mechanisms that pose a risk during pregnancy and lactation. Pregnancy involves physiological changes that facilitate fetal exposure to cannabis. The fetus vulnerability to the endocannabinoid system during the stage of neurological development raises the suspicion of adverse effects linked to the exposure to cannabis and derivatives. The objective of this paper is to update the scientific data regarding the effects of the use of cannabis and derivatives during pregnancy and lactation. We carried out a descriptive review of scientific articles published in peer-reviewed journals between January 2010 and December 2018. We included a database analysis and used combinations of terms in English and Spanish: "marijuana", "cannabis", "cannabinoids", "pregnancy", "lactation". The effects of marijuana consumption during pregnancy are not conclusive, although there is growing evidence that it might be linked to birth alterations, such as low birth weight and neurodevelopmental damage remaining until late childhood and adolescence. No link was found to other indicators, such as perinatal mortality and pre-term births. The self-reported studies analyzed posed various weaknesses, mainly uncertainties and confusion regarding the consumption of other substances. So far, we have enough evidence to adopt a precautionary principle and to recommend against the use of cannabis during pregnancy and lactation.

Resumo: O consumo de cannabis é menor do que o do álcool e do tabaco. A maior frequência de consumo ocorre durante a idade reprodutiva das pessoas. Os canabinóides têm características cinéticas e mecanismos de ação que representam um risco durante a gravidez e amamentação. A gravidez envolve alterações fisiológicas que facilitam a exposição fetal à cannabis. A vulnerabilidade do feto ao sistema endocanabinóide durante o estágio de desenvolvimento neurológico levanta a suspeita de efeitos adversos ligados à exposição à cannabis e seus derivados. O objetivo deste paper é atualizar os dados científicos sobre os efeitos do uso de cannabis e derivados durante a gestação e amamentação. Realizamos uma revisão descritiva de artigos científicos publicados em periódicos revisados por pares entre janeiro de 2010 e dezembro de 2018. Incluímos uma análise de banco de dados e utilizamos combinações de termos em inglês e espanhol: "maconha", "cannabis", "canabinóides", " gravidez "," amamentação". Os efeitos do consumo de cannabis durante a gravidez não são conclusivos, embora haja evidências crescentes de que o consumo possa estar relacionado a alterações no nascimento, como baixo peso ao nascer e dano ao desenvolvimento neurológico até os estágios da infância e adolescência tardias. Não foi encontrada relação com outros indicadores, como mortalidade perinatal e nascimentos pré-termo. Os estudos analisados apresentaram várias fragilidades, principalmente autorrelato e incertezas e confusão em relação ao consumo de outras substâncias. Até agora, temos evidências suficientes para adotar um princípio de precaução e recomendar contra o uso de cannabis durante a gravidez e a lactação.

Intoxicación aguda intencional por metformina en una adolescente: a propósito de un caso clínico / Intentional acute metformin overdose in an adolescent. Case report / Intoxicação intencional aguda com metformina num adolescente. Relato de caso

Resumen: Las intoxicaciones agudas en los servicios de emergencia pediátrica ocupan un lugar importante dentro de la patología de urgencia por su potencial riesgo vital. El Centro de Información y Asesoramiento Toxicológico (CIAT) recibe anualmente un promedio de 10.000 consultas, el 45% corresponde a pacientes menores de 15 años. Del total de consultas (41.465) en el período 2003-2006, el 5,4% correspondieron a circunstancias voluntarias suicidas en el grupo etario de 10-15 años. Los medicamentos fueron los agentes más frecuentemente involucrados. Describimos el caso de una adolescente con una intoxicación aguda grave intencional suicida con metformina. Las manifestaciones clínicas más importantes fueron náuseas, vómitos, dolor abdominal, hipotensión mantenida, bradicardia transitoria, acidosis metabólica, hiperlactacidemia e hipoglicemia sintomática. No se evidenció la presencia de hipoglicemiantes orales, ni fármacos cardiovasculares en el escenario. La ingesta de metformina presenta habitualmente al inicio síntomas poco específicos, desarrollando acidosis láctica hasta 8 horas posingesta. Los síntomas graves en la intoxicación con metformina no son frecuentes. La presencia de síntomas digestivos con acidosis metabólica y lactato elevado debe hacer sospechar una intoxicación por metformina. La hipotensión es un signo ominoso que requiere soporte hemodinámico urgente y mantenido, siendo de mal pronóstico. Otra preocupación después de una sobredosis de metformina es la progresión a la acidosis láctica. Esta situación metabólica determinará el pronóstico, dado que es conocido el efecto deletéreo en la función cardiovascular. La muerte después de la aparición de acidosis láctica puede ser rápida en ausencia de hemodiálisis.

Summary: Acute intoxications have a key role in pediatric emergency services, due to its potential life threat. The Montevideo Poison Control Center annually receives an average of 10,000 consultations per year, 45% from patients under 15 years of age. Of the total number of consultations (41,465) in 2003-2006, 5.4% accounted for voluntary suicidal circumstances in the 10 -15 year-old age group. Medications were the most frequent agents used. We hereby describe the case of a teenager who used Metformin to intend am intentional severe acute poisoning suicide. The main clinical manifestations were nausea, vomiting, abdominal pain, maintained hypotension, transient bradycardia, metabolic acidosis, hyperlactatemia and symptomatic hypoglycemia. There was no evidence of oral hypoglycemic agents or cardiovascular drugs at stake. Metformin intake usually shows symptoms that are not very specific at first, and lactic acidosis usually occurs up to 8 hours after the intake. Metformin poisoning symptoms are rarely severe. The presence of digestive symptoms, metabolic acidosis and elevated lactate should suggest Metformin poisoning. Hypotension is an ominous sign that requires urgent and continuous hemodynamic support and it is often poorly diagnosed. Another concern after Meformin overdose is the progression to lactic acidosis. This metabolic situation will determine the prognosis to be adopted, due to the deleterious effect on cardiovascular function. In absence of hemodialysis, death after the onset of lactic acidosis can be rapid.

Resumo: As intoxicações agudas têm um papel fundamental nos serviços de emergência pediátrica, devido a seu potencial de ameaça à vida. O Centro de Controle de Intoxicações de Montevidéu recebe anualmente uma média de 10.000 consultas por ano, 45% de pacientes com menos de 15 anos de idade. Do total de consultas (41.465) em 2003-2006, 5,4% aconteceram por circunstâncias de suicídio voluntário nas idades de 10 a 15 anos. Os agentes mais frequentemente utilizados foram os medicamentos. Descrevemos aqui o caso de um adolescente que usou Metformina para intentar um suicídio intencional por intoxicação aguda grave. As principais manifestações clínicas foram náuseas, vómitos, dor abdominal, hipotensão mantida, bradicardia transitória, acidose metabólica, hiperlactatemia e hipoglicemia sintomática. Não houve evidência de hipoglicemiantes orais ou drogas cardiovasculares. A ingestão de Metformina geralmente apresenta sintomas que não são específicos no início, e a acidose láctica geralmente ocorre até 8 horas após a ingestão. Os sintomas de envenenamento por Metformina raramente são graves. A presença de sintomas digestivos, acidose metabólica e lactato elevado pode sugerir intoxicação por Metformina. A hipotensão é uma sinal de risco que requer suporte hemodinâmico urgente e contínuo e, muitas vezes, é pouco diagnosticado. Outra preocupação após a overdose de Meformina é a progressão para a acidose láctica. Essa situação metabólica determinará o prognóstico a ser adotado, devido ao efeito deletério sobre a função cardiovascular. No caso de ausência de hemodiálise, a morte após o início da acidose láctica pode ser rápida.

2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes BHV-1 infection in mammalian cells by interfering with iron homeostasis regulation.

Mammalian cells require iron to satisfy metabolic needs or to accomplish specialized functions, and DNA viruses, like bovine herpesvirus 1 (BHV-1), require an iron-replete host to efficiently replicate, so that iron bioavailability is an important component of viral virulence. Cellular iron metabolism is coordinately controlled by the Iron Regulatory Proteins (IRP1 and IRP2), whose activity is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a current and persistent environmental contaminant. Considering that TCDD enhances BHV-1 replication, herein we analyzed the effects of TCDD on iron metabolism during BHV-1 infection in MDBK cells, and presented evidences of a divergent modulation of IRP1 and IRP2 RNA-binding capacity. Moreover, an up-regulation of transferrin receptor 1 (TfR1) and a concomitant down-regulation of ferritin were observed. This scenario led to an expansion of the labile iron pool (LIP) and induces a significant enhance of viral titer, as confirmed by increased levels of BHV-1 infected cell protein 0 (bICP0), the major transcriptional regulatory protein of BHV-1. Taken together, our data suggest that TCDD increases the free intracellular iron availability thereby promoting the onset of BHV-1 infection and rendering bovine cells more vulnerable to the virus.

High Fat Diet Induces Liver Steatosis and Early Dysregulation of Iron Metabolism in Rats.

This paper is dedicated to the memory of our wonderful colleague Professor Alfredo Colonna, who passed away the same day of its acceptance. Fatty liver accumulation, inflammatory process and insulin resistance appear to be crucial in non-alcoholic fatty liver disease (NAFLD), nevertheless emerging findings pointed an important role also for iron overload. Here, we investigate the molecular mechanisms of hepatic iron metabolism in the onset of steatosis to understand whether its impairment could be an early event of liver inflammatory injury. Rats were fed with control diet or high fat diet (HFD) for 5 or 8 weeks, after which liver morphology, serum lipid profile, transaminases levels and hepatic iron content (HIC), were evaluated. In liver of HFD fed animals an increased time-dependent activity of iron regulatory protein 1 (IRP1) was evidenced, associated with the increase in transferrin receptor-1 (TfR1) expression and ferritin down-regulation. Moreover, ferroportin (FPN-1), the main protein involved in iron export, was down-regulated accordingly with hepcidin increase. These findings were indicative of an increased iron content into hepatocytes, which leads to an increase of harmful free-iron also related to the reduction of hepatic ferritin content. The progressive inflammatory damage was evidenced by the increase of hepatic TNF-α, IL-6 and leptin, in parallel to increased iron content and oxidative stress. The major finding that emerged of this study is the impairment of iron homeostasis in the ongoing and sustaining of liver steatosis, suggesting a strong link between iron metabolism unbalance, inflammatory damage and progression of disease.

Exposición no intencional a cannabis en niños en el marco de la regulación del mercado en Uruguay. Reporte de casos asistidos en el Departamento de Emergencia del Centro Hospitalario Pereira Rossell entre marzo y junio de 2017 / Children unintentionally exposed to cannabis within the framework of the Uruguayan Cannabis Sale Regulation. Cases assisted at the Emergency Department of the Pereira Rossell Hospital between March and June 2017 / Exposição não intencional à cânabis em crianças no âmbito do regulamento das vendas do cânabis no Uruguai. Relatório de casos atendidos no Serviço de Emergência do Hospital Pereira Rossell entre março e junho de 2017

Resumen: Introducción: la marihuana es la sustancia de abuso más consumida en América y Europa después del alcohol. En Uruguay la prevalencia es cercana a 23%. El principio activo delta 9-tetrahidrocannabinol es responsable de los efectos psicoactivos. La principal fuente en un niño es una parte de la planta, cigarrillo o comestible con cannabis proveniente de un familiar o vecino. La intoxicación puede ser más severa en niños que en adultos. En Uruguay, en 2013, se aprobó la ley 19.172 que regula el mercado de cannabis, generando un nuevo escenario con potencial riesgo para la población pediátrica. Objetivo: comunicar casos clínicos de intoxicación aguda no intencional por cannabis asistidos entre marzo y junio de 2017, analizar circunstancias de exposición, manifestaciones clínicas, severidad y evolución. Observación clínica: cuatro niños (9 meses, 1, 2 y 8 años) fueron asistidos. En todos ellos la vía de ingreso fue oral en ambiente doméstico. Presentaron síntomas neurológicos agudos: depresión de conciencia, convulsiones, distonías, ataxia, irritabilidad. Requirieron medidas de sostén, descontaminación digestiva y exámenes de laboratorio ampliado. El screening en orina fue positivo en cuatro casos. En dos se realizó la técnica confirmatoria. Aplicando el Poisoning Severity Score, todos sufrieron intoxicación moderada. Se asistieron en conjunto con toxicólogo clínico. Conclusiones: los niños que presentan síntomas predominantemente neurológicos de instalación aguda sin una causa evidente, pueden presentar intoxicación aguda por cannabis, sobre todo cuando en el entorno doméstico hay consumo, cultivo o ambos. Debemos mantener una vigilancia activa. Seguramente futuras investigaciones contribuirán a definir la necesidad de establecer estrategias de prevención destinadas a la población infantil con el objetivo de disminuir el potencial efecto no deseado de este nuevo escenario.

Summary: Introduction: marijuana is most highly consumed abuse substance in America and Europe after alcohol. In Uruguay, the prevalence is close to 23%. The active ingredient, delta 9-tetrahydrocannabinol, is responsible for its psychoactive effects. The main source of access for a child involves a relative and/or neighbor. Intoxication may be more severe in children, In 2013,.cannabis-sale regulating Act 19.172 was approved in Uruguay, and it generated a new potentially risky scenario for children. Objective: report clinical cases of severe unintentional intoxication from cannabis between March and June 2017, and analyze circumstances that led to exposure, clinical manifestations, severity and evolution. Clinical observation: 4 children (9 months, 1, 2 and 8 years of age) were assisted. In all cases, they had ingested cannabis in their home environment. They presented severe neurological symptoms: depressed level of consciousness, convulsive seizures, dystonia, ataxia, irritability. They required supportive measures, digestive decontamination and additional laboratory tests. Urine screening was positive in 4 cases. In 2, we performed confirmatory technique. As per the Poisoning Severity Score, all children suffered moderate intoxication. They were assisted jointly by a clinical toxicologist. Conclusions: children showing predominantly acute neurological symptoms with no apparent cause can be the subject of severe cannabis intoxication, especially when cannabis consumption takes place in their household environments. Surveillance is needed and future research will certainly contribute to the creation of prevention strategies with the purpose of reducing the potential unwanted consequences of this new scenario for children.

Resumo: Introdução: a maconha é a substância do abuso mais consumida na América e na Europa depois do álcool. No Uruguai, a prevalência é próxima de 23%. O ingrediente ativo delta 9-tetrahydrocannabinol é responsável pelos efeitos psicoativos. A principal fonte de acesso à marijuana por parte duma criança é ingerir uma parte da planta, cigarro ou comestível com cânabis de um parente e / ou vizinho. A intoxicação pode ser mais grave em crianças do que em adultos. No Uruguai, em 2013, a Lei 19.172 foi aprovada e regulou a venda de cânabis, gerando um novo cenário com risco potencial para as crianças. Objetivo: relatar casos clínicos de intoxicação aguda não intencional por cânabis atendidos entre março e junho de 2017, analisar as circunstâncias de exposição, manifestações clínicas, gravidade e evolução. Observação clínica: 4 crianças (9 meses, 1, 2 e 8 anos de idade) foram atendidas. Todos eles ingeriram cânabis num ambiente doméstico. Apresentaram sintomas neurológicos agudos: depressão da consciência, convulsões, distonia, ataxia, irritabilidade. Eles precisaram de medidas de suporte, descontaminação digestiva e testes de laboratório adicionais. O screening de urina foi positivo em 4 casos. Em 2, a técnica confirmatória foi realizada. Utilizando o Poisoning Severity Score, todos sofreram intoxicação moderada. Eles foram assistidos conjuntamente pelo toxicologista clínico. Conclusões: é possível que crianças que apresentam sintomas neurológicos predominantemente de instalação aguda sem causa evidente, apresentem intoxicação aguda por cânabis, especialmente quando existe consumo no ambiente ou na cultura domésticos. Nós devemos manter uma vigilância ativa. Com certeza, futuras pesquisas contribuirão para definir estratégias de prevenção para crianças, com o objetivo de reduzir o potencial efeito indesejado desse novo cenário.

Exposición a cocaína en niños menores de 5 años: serie de casos / Cases of exposure to cocaine in children under 5 years of age / Casos de exposição à cocaína em crianças menores de 5 anos

Resumen: Los hijos de madres consumidoras de cocaína están expuestos en la etapa prenatal y durante la lactancia. Asimismo, están en riesgo de ingesta no intencional o contacto mucoso de restos de la sustancia a su alcance y de inhalación pasiva del humo de cocaínas fumables en ambientes cerrados. Objetivo: describir el perfil epidemiológico de la exposición a cocaína en los niños menores a 5 años en nuestro país analizando circunstancias de exposición, manifestaciones clínicas y complicaciones agudas. Material y método: estudio observacional, descriptivo, retrospectivo de las consultas reportadas a un centro de toxicología en el período 2010-2016 de niños de hasta 5 años de edad con screening positivo para cocaína en orina. Resultados: se incluyeron 18 casos, se analizaron 17 por insuficiencia de datos. Todos fueron menores de 2 años. Predominaron manifestaciones neurológicas (12/17): convulsiones (7/12). Otras manifestaciones incluyeron: taquicardia (2/17), hipertensión (3/17), elevación de creatinfosfokinasa total (4/17) y rabdomiólisis (2/17). Catorce pacientes se encontraban en lactancia pero solo siete madres presentaron screening positivo. El screening de cocaína fue el criterio de selección por su baja tasa de falsos positivos. Esta serie coincide con la literatura en edad de riesgo para exposición a cocaína, planteándose la lactancia como principal vía de ingreso. Sin embargo, los resultados muestran que otras vías de ingreso son posibles. Las convulsiones fueron la forma de presentación más frecuente. Conclusiones: los casos reportados evidencian la necesidad de mantener un alto índice de sospecha ante síntomas neurológicos o cardiovasculares, evidencian el valor de los tests de screening y expanden las circunstancias de riesgo.

Summary: Children born of cocaine-using mothers are exposed to the substance during the prenatal and breastfeeding periods. They are also at risk of cocaine unintentional ingestion or mucosal contact when the substance remains within their reach or at risk of passive inhalation of smoke from cocaine smoked in confined environments. Objective: describe the cocaine exposure epidemiological profile in children under 5 years of age in our country, analyze circumstances of exposure, clinical manifestations and acute complications. Material and methods: observational, descriptive and retrospective study of the consultations reported to a Toxicological Center during 2010-2016 of children up to 5 years of age with positive urine cocaine screening. Results: we included 18 cases, but only 17 were analyzed, due to insufficient data. All children were under 2 years of age. Neurological manifestations were predominant (12/17): seizures (7/12). Other manifestations included tachycardia (2/17), hypertension (3/17), total creatinine phosphokinase increase (4/17) and rhabdomyolysis (2/17). Fourteen patients have been breastfed, but only seven mothers showed positive screening. Cocaine positive screening was the selection criteria because of its low false positive rate. This series matches the literature regarding the main age risk regarding cocaine exposure; breastfeeding was considered the main source of exposure. However, the results show that other sources are possible. Seizures were the most frequent form of presentation. Conclusions: reported cases show that we should be cautious regarding neurological or cardiovascular symptoms, support the implementation of screening tests and expand risk circumstances.

Resumo: Os filhos de mães que usam cocaína estão expostos durante a fase pré-natal e durante a lactação. Da mesma forma, correm o risco de ingestão não intencional ou contato mucoso de restos da substância ao seu alcance e de inalação passiva de fumaça de cocaína fumável em ambientes fechados. Objetivo: descrever o perfil epidemiológico da exposição à cocaína em crianças menores de cinco anos de idade em Uruguai, analisar as circunstâncias de exposição, as manifestações clínicas e as complicações agudas. Material e métodos: estudo observacional, descritivo retrospectivo das consultas reportadas a um Centro de Toxicologia no período 2010-2016, realizado a crianças de até 5 anos de idade com triagem positiva para cocaína na urina. Resultados: nós incluímos 18 casos e analisamos 17 devido a dados insuficientes. Todos tinham menos de 2 anos de idade. As principais manifestações neurológicas (12/17) foram: convulsões (7/12). Outras manifestações incluíram: taquicardia (2/17), hipertensão (3/17), elevação total da creatinofosfoquinase (4/17) e rabdomiólise (2/17). 14 pacientes eram lactantes, mas apenas 7 mães tiveram triagem positiva. O rastreamento de cocaína foi o critério de seleção devido à baixa taxa de falsos positivos. Esta série coincide com a literatura sobre a idade de risco para a exposição à cocaína, considerando a amamentação como a principal via de entrada da substância no organismo. No entanto, os resultados mostram que existem outras vias de entrada da substancia no organismo. A forma de apresentação mais frequente foram as convulsões. Conclusões: os casos relatados mostram que devemos ser cautelosos quanto aos sintomas neurológicos ou cardiovasculares, apoiar a implementação de testes de triagem e expandir as circunstâncias de risco.