RESUMEN
Vasoreactive pulmonary arterial hypertension (PAH) in children is a form of idiopathic PAH that responds to vasoreactive testing with nitric oxide (NO) by a significant decrease of pulmonary vascular resistances and pressure. Oral calcium channel antagonists (CCA) that allow pulmonary arterial vasodilation are the treatment of choice. The therapeutic effect is strongly depending on adequate drug intake. In growing children, drug dose must be adapted to weight. In case of unavailability of low-dose pharmaceutical preparations, officinal formulations become mandatory. Officinal formulations may be related to a multitude of errors at different steps including prescription, transcription, preparation and administration. This may have life-threatening consequences for the child.To illustrate this, we report a case of a compounding error with underdosage of CCA, leading to acute cardiovascular failure in an adolescent with vasoreactive PAH.
L'hypertension artérielle pulmonaire (HTAP) vasoréactive chez l'enfant est une forme d'HTAP idiopathique qui répond au test de vasoréactivité au monoxyde d'azote (NO) par une diminution significative des pressions et résistances vasculaires pulmonaires. Le traitement de choix de cette forme d'HTAP est l'administration d'antagonistes des canaux calciques (ACC) par voie orale. Ce traitement entraîne une vasodilatation artérielle pulmonaire, elle-même étroitement dépendante de la prise adéquate du médicament. Chez les enfants en croissance, la dose du médicament doit être adaptée au poids. De façon générale, en l'absence de préparation à faible dose disponible dans les laboratoires pharmaceutiques, l'utilisation de formulations officinales devient obligatoire. De la prescription à l'administration, en passant par la transcription et la préparation, de nombreuses erreurs humaines et techniques peuvent survenir qui peuvent impacter la morbi-mortalité de l'enfant. Nous rapportons le cas d'une adolescente avec HTAP vasoréactive chez qui une erreur de préparation magistrale avec sous-dosage de l'ACC a conduit à une décompensation cardio-vasculaire aiguë et discutons de mesures préventives potentielles.
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Hipertensión Pulmonar , Adolescente , Humanos , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Óxido Nítrico/uso terapéuticoRESUMEN
PURPOSE: Humans are daily exposed to many environmental pollutants, some of which being suspected to be thyroid disruptors. Some populations could be particularly susceptible to thyroid disruption, such like diabetics due to the well-known relation between the thyroid function and the control of carbohydrate homeostasis by pancreas. Therefore, the aim of this study was to investigate the associations between the exposure to several persistent and non-persistent chemicals and thyroid hormones levels in children with type 1 diabetes. METHODS: Blood and urine sample were collected from 54 children diagnosed for type 1 diabetes mellitus. The concentrations of 7 phthalate metabolites, 4 parabens, 7 bisphenols, benzophenone 3 and triclosan were measured in urine, while 15 organochlorine pesticides, 4 polychlorinated biphenyls (PCBs) and 7 perfluoroalkyl substances were analyzed in serum samples. In the same time, the blood levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and glycated hemoglobin (Hb1Ac) were determined. RESULTS: We highlighted positive associations between serum perfluorohexane sulfonate and urinary monoethylphthalate levels, and TSH level in blood. We also found that PCB 138 was positively associated to fT4 while urinary levels of bisphenol F were negatively correlated to this hormone. Finally, we observed positive associations between Hb1Ac levels and the contamination by PCB 153 and two urinary phthalate metabolites: mono-2-ethyl-5-hydroxyhexyl phthalate and mono-2-ethyl-5-oxoxyhexyl phthalate. CONCLUSION: Our results showed that our small cohort of children with type 1 diabetes mellitus is potentially susceptible to thyroid disruptions by some pollutants. Moreover, for these children, both di-(2-ethylhexyl) phthalate metabolites would potentially hamper the glucose homeostasis. Nevertheless, additional studies are mandatory to further explore these findings.
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Diabetes Mellitus Tipo 1 , Dietilhexil Ftalato , Disruptores Endocrinos , Contaminantes Ambientales , Ácidos Ftálicos , Humanos , Niño , Disruptores Endocrinos/orina , Bélgica , Ácidos Ftálicos/metabolismo , Hormonas Tiroideas , Dietilhexil Ftalato/orina , Tirotropina , Homeostasis , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
OBJECTIVES: Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. METHODS: Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. RESULTS: A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. CONCLUSIONS: The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability.
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Pruebas de Enzimas , Etanol , Bélgica , HumanosRESUMEN
A human biomonitoring study was carried out in 2015 within an adult population living in Liege (Belgium). Some phthalate metabolites and parabens were measured in the urine of 252 participants, and information were collected about their food habits, life styles and home environment to identify some predictors of exposure. Concomitantly, an awareness campaign was initiated by the Provincial Authorities of Liege and spread over 2 years. Three years later (2018), 92 of the initial participants provided again urine samples, and the levels of phthalate metabolites, phthalate substitute (DINCH), parabens, bisphenol-A and bisphenol alternatives (bisphenol-S, -F, -Z, -P) were determined and compared to those obtained in 2015 to assess time trends. In 2015, methyl- and ethylparaben were the most abundant parabens (P50 = 9.12 µg/L and 1.1 µg/L respectively), while propyl- and butylparaben were sparsely detected. Except for mono-2-ethylhexyl phthalate and 6-OH-mono-propyl-heptyl phthalate, all other targeted phthalate metabolites were positively quantified in most of the urine samples (between 89 and 98%) with median concentrations ranging between 2.7 µg/L and 21.3 µg/L depending on the metabolite. The multivariate regression models highlighted some significant associations between urinary phthalate metabolite or paraben levels and age, rural or urban character of the residence place, and the use of some personal care products. However, all determination coefficients were weak meaning that the usual covariates included in the models only explained a small part of the variance. Between 2015 and 2018, levels of parabens and phthalate metabolites significantly decreased (from 1.3 to 2.5 fold) except for monoethyl phthalate which seemed to remain quite constant. Contrariwise, all bisphenol alternatives and DINCH metabolites were measured in higher concentrations in 2018 vs 2015 while BPA levels did not differ significantly. However, it was not feasible to unequivocally highlight an impact of the awareness campaign on the exposure levels of the population.
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Contaminantes Ambientales , Ácidos Ftálicos , Adulto , Bélgica , Compuestos de Bencidrilo/orina , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Humanos , Parabenos/análisis , Fenoles , Ácidos Ftálicos/orina , PlastificantesRESUMEN
BACKGROUND: Intra-partum cefazolin is used to prevent group B Streptococcus (GBS) vertical transmission in mothers allergic to penicillin without a history of anaphylaxis. OBJECTIVES: To investigate the maternal cefazolin dose-exposure relationship and subsequent maternal and neonatal target attainment at delivery. METHODS: Data were obtained from 24 healthy, GBS-colonized pregnant women (20-41 years), undergoing vaginal delivery (gestational age ≥37 weeks). During labour, all women received a 2 g cefazolin IV infusion. Eight hours later, eight women received another 1 g in the event of delayed (>8 h) delivery. Next to maternal plasma concentrations (up to 10 per dosing interval, until delivery), venous and arterial umbilical cord concentrations were determined at delivery. Target attainment in maternal/neonatal plasma was set at 1 mg/L for 60% of the dosing interval (unbound cefazolin, worst-case clinical breakpoint). A population pharmacokinetic (popPK) model was built (NONMEM 7.4). ClinicalTrials.gov Identifier: NCT01295606. RESULTS: At delivery, maternal blood and arterial umbilical cord unbound cefazolin concentrations were >1 mg/L in 23/24 (95.8%) and 11/12 (91.7%), respectively. The popPK of cefazolin in pregnant women was described by a two-compartment model with first-order elimination. Two additional compartments described the venous and arterial umbilical cord concentration data. Cefazolin target attainment was adequate in the studied cohort, where delivery occurred no later than 6.5 h after either the first or the second dose. PopPK simulations showed adequate maternal and umbilical cord exposure for 12 h following the first dose. CONCLUSIONS: PopPK simulations showed that standard pre-delivery maternal cefazolin dosing provided adequate target attainment up to the time of delivery.
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Antibacterianos , Cefazolina , Adulto , Femenino , Humanos , Recién Nacido , Plasma , Embarazo , Streptococcus agalactiae , Cordón Umbilical , Adulto JovenRESUMEN
Previous years, the incidence of autoimmune thyroid diseases has increased worldwide. The presence of many pollutants in the environment suspected to be thyroid disruptors may have contributed to the observed increase. Unfortunately, the results from epidemiological studies assessing the association between pollution and thyroid disorders remain inconsistent, maybe due to a nearly complete neglect of the mixture effect. The blood levels of 12 brominated flame retardants, 3 polychlorinated biphenyls, 16 organochlorine pesticides, 7 perfluoroalkyl substances and 16 phenolic organohalogens were measured in 35 hypothyroid and 44 hyperthyroid volunteers and in 160 individuals from the general population designed as controls. Weighted quantile sum (WQS) regressions were performed to compute indexes representing the mixture of POPs, and we assessed the relations with thyroid disorders. Nineteen pollutants were detected in more than 40% of the individuals and were thus included in the WQS indexes. The WQS index was statistically significantly associated with an increased odds of hypothyroidism (odds ratio (OR) = 98.1; 95% CI: 5.51-1747) with the highest weights attributed to PCB 138 (w = 0.210), 3-OH-CB 180 (w = 0.197), 4-OH-CB 146 (w = 0.188), 4',4-DDE (w = 0.156) while there were no evidence of a relation with increased odds of hyperthyroidism. Given the relative low number of individuals included in the present investigation, standard WQS methodology could not be used, this study should thus be considered as a preliminary, hypothesis-generating study. Nevertheless, these results highlighted the importance of considering the potential effect of chemical mixture when studying endocrine disruptors.
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Exposición a Riesgos Ambientales , Contaminantes Ambientales , Glándula Tiroides , Bélgica , Humanos , Hidrocarburos Clorados , Plaguicidas , Bifenilos PolicloradosRESUMEN
OBJECTIVES: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia. PATIENTS AND METHODS: Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method. RESULTS: Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma. CONCLUSIONS: The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.
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Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Infección Hospitalaria/tratamiento farmacológico , Neumonía Bacteriana/tratamiento farmacológico , Tienamicinas/administración & dosificación , Tienamicinas/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Femenino , Humanos , Infusiones Intravenosas , Masculino , Meropenem , Persona de Mediana Edad , Plasma/química , Estudios Prospectivos , Mucosa Respiratoria/química , Adulto JovenRESUMEN
In the present study, we investigated the temporal within-person variability of the exposure biomarker for phthalates, parabens and benzophenone-3 (BP3) in 32 Belgian adults, each providing 11 urine spots during 4 months. We calculated the intraclass coefficient correlation (ICC), the sensitivity and the specificity to assess the temporal reproducibility and to investigate the predictive ability of the spot measurements for these classes of chemicals. Additionally, we explored the temporal variability of the estimation of the cumulative risk of exposure to phthalates (hazard index; HI). We observed fair ICC ranging from 0.55 to 0.68 for parabens, monoethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and BP3, but lower ICC, from 0.20 to 0.49, for monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxo-hexyl phthalate (5-oxo-MEHP) and mono-2-ethyl-5-hydroxy-hexyl phthalate (5-OH-MEHP). The ICC estimated for HI (0.49) reflected a moderate reproducibility. The measurements in spot samples were moderate to good predictor of the 4-month level of exposure for parabens, MEP, MnBP, MiBP, BP3 and HI (sensitivity ranging from 0.67 to 0.77), but lower predictor for MEHP, 5-oxo-MEHP, 5-OH-MEHP and MBzP (sensitivity ranging from 0.58 to 0.63). The sensitivity could be increased when several spot urinary levels were averaged to predict the long-term level of exposure. Globally, our results indicate that a single spot measurement seems to correctly represent the long-term exposure for parabens, BP3, MEP, MiBP and HI. Additional spot samples seemed to be needed for the proper exposure assessment of the other target compounds.
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Benzofenonas/orina , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Parabenos/farmacocinética , Ácidos Ftálicos/orina , Adulto , Bélgica , Benzofenonas/metabolismo , Biomarcadores/orina , Humanos , Parabenos/metabolismo , Ácidos Ftálicos/metabolismo , Reproducibilidad de los Resultados , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.
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Monitoreo del Ambiente/métodos , Contaminación de Alimentos/análisis , Preferencias Alimentarias , Cabello/química , Compuestos de Metilmercurio/análisis , Alimentos Marinos , Contaminantes Químicos del Agua/análisis , Adulto , Niño , Interpretación Estadística de Datos , Europa (Continente) , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Madres , Proyectos Piloto , Población Rural , Encuestas y Cuestionarios , Población UrbanaRESUMEN
BACKGROUND/AIMS: Heroin-assisted treatment (HAT) can improve the condition of heroin addicts still using street heroin after a methadone treatment. In Belgium, a new trial compared the efficacy of a HAT to existing methadone maintenance treatment. METHODS: In this randomised controlled trial, HAT was limited to 12 months. Participants were assessed every 3 months. They were responders if they showed improvement on the level of street heroin use, health or criminal involvement. RESULTS: 74 participants were randomised in the trial. The experimental group (n = 36) counted 30% of responders more than the control group (n = 38) at each assessment point (p < 0.05), except at 12 months where the difference (11%) was no longer significant (p = 0.35). Still, after 12 months, participants in the experimental group reported significantly greater improvements (p < 0.05) than the control group on the level of street heroin use and on the level of physical and mental health. Both groups reported significantly less criminal acts after 12 months (p < 0.001), but with no significant difference between the groups. CONCLUSIONS: This trial confirms the short-term efficacy of HAT for severe heroin addicts, who already failed methadone treatment.
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Dependencia de Heroína/tratamiento farmacológico , Heroína/uso terapéutico , Narcóticos/uso terapéutico , Tratamiento de Sustitución de Opiáceos/métodos , Adulto , Bélgica , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: Strong experimental evidence exists that several endocrine disrupting chemicals (EDCs) have neurobehavioral toxicity. However, evidence of associations between prenatal exposure and child's cognitive development is inconsistent. Moreover, toxicants are generally analyzed one by one without considering aggregate effects. We examined here the impact of a prenatal exposure to a mixture of persistent organic pollutants (POPs) on intellectual abilities in preschool children, and compared their effects to those described in the literature. METHODS: Sixty-two children were included in a longitudinal cohort. Four organochlorine pesticides, four polychlorinated biphenyls (PCBs) and seven perfluorinated compounds (PFCs) were measured in cord blood. Intellectual abilities were assessed at 6 years of age using the Wechsler Preschool and Primary Scale of Intelligence 4th ed. (WPPSI-IV). We examined the associations between a mixture of POPs and cognitive performances using principal components approach (PCA) and weighted quantile sum (WQS) regression taking sex difference into account. RESULTS: No negative correlation was found when analyses were performed on boys and girls together. In sex-stratified analyses, lower scores in full scale intelligence quotient (FSIQ) and fluid reasoning index (FRI) were observed in boys most exposed to a mixture of POPs. Increase of the WQS index was also associated with lower verbal comprehension index (VCI) scores in girls only. No other negative correlation was found using both WQS and PCA models. CONCLUSION: Our study suggests deleterious associations between antenatal exposure to a mixture of POPs and sex-specific cognitive level, clarifying some trends described in the literature.
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Inteligencia , Contaminantes Orgánicos Persistentes , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Masculino , Niño , Inteligencia/efectos de los fármacos , Bifenilos Policlorados/sangre , Bifenilos Policlorados/toxicidad , Plaguicidas/toxicidad , Preescolar , Hidrocarburos Clorados/toxicidad , Hidrocarburos Clorados/sangre , Desarrollo Infantil/efectos de los fármacos , Fluorocarburos/toxicidad , Fluorocarburos/sangre , Estudios Longitudinales , Sangre Fetal/química , Disruptores Endocrinos/toxicidad , Cognición/efectos de los fármacos , Pruebas de Inteligencia , AdultoRESUMEN
Cannabidiol (CBD) has multiple therapeutic benefits that need to be maximized by optimizing its bioavailability. Numerous formulations are therefore being developed and their pharmacokinetics need to be studied, requiring analytical methods and data from intravenous administration. As CBD is susceptible to hepatic metabolism, the requirement of any method is to quantify metabolites such as 7-COOH-CBD. We demonstrated that CBD and 7-COOH-CBD could be simultaneously and correctly quantified in piglet plasma by using an UHPLC-MS/MS technique. The validated method allowed for an accurate bioanalysis of an intravenously injected solution consisting of CBD-HPßCD complexes. The experimental pharmacokinetic profile of CBD showed multi-exponential decay characterized by a fast apparent distribution half-life (0.25 h) and an elimination half-life of two hours. The profile of 7-COOH-CBD was not linked with the first-pass metabolism, since 80% of the maximum metabolite concentration was reached at the first sampling time point, without any decrease during the period of study. A two-compartment model was optimal to describe the experimental CBD profile. This model allowed us to calculate macro-micro constants and volumes of distribution (Vss = 3260.35 ± 2286.66 mL) and clearance (1514.5 ± 261.16 mL·h-1), showing that CBD is rapidly distributed to peripheral tissues once injected and slowly released into the bloodstream.
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Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.
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Ácidos Alcanesulfónicos , Disruptores Endocrinos , Fluorocarburos , Contaminantes Orgánicos Persistentes , Bifenilos Policlorados , Neoplasias de la Tiroides , Humanos , Estudios de Casos y Controles , Fluorocarburos/sangre , Fluorocarburos/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Disruptores Endocrinos/sangre , Disruptores Endocrinos/efectos adversos , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/inducido químicamente , Neoplasias de la Tiroides/genética , Bifenilos Policlorados/sangre , Bifenilos Policlorados/efectos adversos , Ácidos Alcanesulfónicos/sangre , Adulto , Contaminantes Orgánicos Persistentes/efectos adversos , Contaminantes Orgánicos Persistentes/sangre , Anciano , Diclorodifenil Dicloroetileno/sangre , Ácidos Decanoicos/sangre , Ácidos Decanoicos/efectos adversos , DDT/sangre , DDT/efectos adversos , Italia/epidemiología , Caprilatos/sangre , Caprilatos/efectos adversos , Proteínas Proto-Oncogénicas B-raf/genética , Ácidos Grasos/sangre , Ácidos Sulfónicos/sangre , Mutación , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
Our study provides the most comprehensive dataset for high-precision radiogenic isotopes of lead (Pb) in blood for the western European population. It investigates their potential for elucidating the contribution of soil Pb to blood Pb using a human biomonitoring survey involving 81 adults and 4 children living in the urban area of Liège (Belgium). Soils in the area show moderate (median of 360 mg/kg) to high (95th percentile of 1000 mg/kg) Pb concentrations, due to former metal processing activities. Blood lead levels (BLL) measured in the study population are, on average, quantitatively consistent with a â¼ 20 % increase due to the exposure to Pb from soils, as estimated by a single-compartment biokinetic model. Consistently, its isotopic composition does not represent an endmember that fully accounts for the variability of Blood lead isotope (BLI) compositions measured in the study population. While some individuals show more thorogenic BLI ratios (relatively more enriched in 208Pb), which could be consistent with a greater exposure to local soils and/or by their country of birth, the BLI data mostly follow a trend roughly parallel to the European Standard Lead Pollution (ESLP) line, within the European leaded gasoline field, even two decades after the withdrawal of this source. Differences in BLI are probably associated with factors related to the presence of Pb in dwellings (pipes, paint) and drinking water distribution system, suggesting that the anthropogenic Pb in use, relevant to human exposure, may contain ore components of different origins, including the Australian Pb ore signature.
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Exposición a Riesgos Ambientales , Plomo , Contaminantes del Suelo , Plomo/sangre , Contaminantes del Suelo/análisis , Contaminantes del Suelo/sangre , Humanos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a Riesgos Ambientales/análisis , Bélgica , Niño , Adulto , Radioisótopos de Plomo/análisis , Monitoreo del Ambiente/métodos , Suelo/química , Monitoreo Biológico/métodosRESUMEN
OBJECTIVE: To determine and compare the concentration of gentamicin in the lower airways and serum of healthy spontaneously breathing dogs after nebulization with 5% undiluted gentamicin during 3 versus 10 minutes. ANIMALS: 10 healthy experimental Beagles. METHODS: This was a prospective crossover study. A standardized bronchoalveolar lavage (BAL) procedure was performed in each dog after 1 week of administration of each of 2 different gentamicin nebulization protocols separated by a 1-week washout period. The 2 protocols consisted of nebulization of 5% undiluted gentamicin (50 mg/mL) twice daily either during 10 minutes per session (± 95 mg; 10-minute protocol) or 3 minutes per session (± 28 mg; 3-minute protocol). BAL fluid (BALF) was obtained under general anesthesia using a bronchoscope within 15 minutes after administration of the last nebulization. Blood was collected within 5 minutes after BALF collection. BALF and serum gentamicin concentrations were determined by particle-enhanced turbidimetric inhibition immunoassay. Concentrations between protocols were compared using a paired t test. RESULTS: Both BALF and serum gentamicin concentrations were higher after the 10-minute protocol compared with the 3-minute protocol (mean ± SD: 2.41 ± 0.87 mg/L vs 1.25 ± 0.31 mg/L, P = .001; and 1.02 ± 0.59 mg/L vs 0.31 ± 0.24 mg/L, P < .0001 in BALF and serum, respectively), while the BALF-to-serum ratio did not differ between the protocols (3.75 [1.37 to 5.75] (median [IQR]) in the 3-minute protocol vs 2.48 [2.02 to 2.67] in the 10-minute protocol; P = .754). CLINICAL RELEVANCE: A 3-minute nebulization of gentamicin seems to achieve sufficient concentrations of gentamicin in the BALF to have good efficacy against aminoglycoside-sensitive bacteria while remaining below the toxic range values in blood.
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Antibacterianos , Gentamicinas , Perros , Animales , Líquido del Lavado Bronquioalveolar , Estudios Cruzados , Estudios Prospectivos , Antibacterianos/uso terapéutico , Lavado Broncoalveolar/veterinaria , Lavado Broncoalveolar/métodosRESUMEN
PURPOSE: Cannabidiol (CBD) has been gaining popularity in recent years. Knowing that CBD products can contain more tetrahydrocannabinol (THC) than expected, interpretation of cannabinoids concentration in urine can be tricky, especially when low amounts of THC and CBD are found. Moreover, interpretation can also be difficult due to interindividual variation in pharmacokinetics. The objective of this work was to take a critical look at the data from our daily practice as a toxicology laboratory. METHODS: We have collected results obtained in a first batch of 1074 urine samples submitted to cannabinoids analysis, and results of cannabinoids content of a second batch of 719 seized materials. RESULTS: CBD was detected in 163 urine specimens (15%). Its concentration was higher than the limit of quantification of 5 ng/mL in 108 samples only (10% of the sampling population). Most of CBD-positive samples were associated with a high THC-COOH concentration (> 500 ng/mL in 63.8% of CBD-positive samples) suggesting only a few CBD consumers in our population. Cannabinoids composition of seized plant materials (drug type at first glance) revealed CBD in 110 of them (15% of the sampling population), with a concentration mostly below 1%. All of the resin samples were CBD positive, and contained more THC compared to flowers. CONCLUSIONS: We can conclude that urine samples from drug-type cannabis users contained a low amount of CBD, what was not described previously. These findings are useful for the interpretation of cannabinoids results in daily practice.
Asunto(s)
Cannabidiol , Cannabinoides , Cannabis , Consumidores de Drogas , Humanos , Cannabidiol/análisis , Cannabinoides/análisis , Extractos Vegetales/farmacocinéticaRESUMEN
BACKGROUND AND AIM: Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life. METHODS: In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quantitation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms. RESULTS: Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) µg/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (ß = 1.23, p = 0.039) and PrP with the retinal tortuosity index (x103)(ß = 1.75, p = 0.0044). Furthermore, we identified inverse associations between MeP and ∑parabens with BMI z-scores (ß = -0.067, p = 0.015 and ß = -0.070, p = 0.014 respectively), and EtP with mean arterial pressure (ß = -0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (ß = 0.10, p = 0.060). CONCLUSIONS: Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature.
Asunto(s)
Enfermedades Cardiovasculares , Exposición a Riesgos Ambientales , Contaminantes Ambientales , Parabenos , Niño , Preescolar , Femenino , Humanos , Masculino , Enfermedades Cardiovasculares/orina , Estudios Transversales , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/análisis , Parabenos/metabolismoRESUMEN
BACKGROUND: Semivolatile organic compounds (SVOCs) comprise several different chemical families used mainly as additives in many everyday products. SVOCs can be released into the air as aerosols and deposit on particulate matter during use by dispersion, evaporation, or abrasion. Phthalates are SVOCs of growing concern due to their endocrine-disrupting effects. Human data on the absorption, distribution, metabolism, and excretion (ADME) of these compounds upon inhalation are almost nonexistent. OBJECTIVE: The goal of this study is to develop a method for repeated inhalation exposures to SVOCs to characterize their ADME in humans. METHODS: We will use diethylhexyl phthalate (DEHP), a major indoor air pollutant, as a model SVOC in this novel protocol. The Swiss official Commission on Ethics in Human Research, Canton de Vaud, approved the study on October 14, 2020 (project-ID 2020-01095). Participants (n=10) will be repeatedly exposed (2 short daily exposures over 4 days) to isotope-labeled DEHP (DEHP-d4) to distinguish administered exposures from background exposures. DEHP-d4 aerosols will be generated with a small, portable, aerosol-generating device. Participants will inhale DEHP-d4-containing aerosols themselves with this device at home. Air concentrations of the airborne phthalates will be less than or equal to their occupational exposure limit (OEL). DEHP-d4 and its metabolites will be quantified in urine and blood before, during, and after exposure. RESULTS: Our developed device can generate DEHP-d4 aerosols with diameters of 2.5 µm or smaller and a mean DEHP-d4 mass of 1.4 (SD 0.2) µg per puff (n=6). As of May 2023, we have enrolled 5 participants. CONCLUSIONS: The portable device can be used to generate phthalate aerosols for repeated exposure in human studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51020.
RESUMEN
Antimicrobials' topical administration efficacy has not been assessed in dogs with upper respiratory tract disease. The aim was to compare the concentration of gentamicin in nasal lavage fluid (NALF) and in serum after three topical protocols. This was a prospective crossover study of ten healthy dogs. Gentamicin was nebulized for a duration of 1 week, twice a day, for 10 min in the first protocol (10-min protocol) and for 3 min in the second protocol (3-min protocol), while the third protocol consisted of the administration of 0.25 mL of gentamicin in each nostril (drop protocol). Median concentrations of gentamicin in NALF were 9.39 µg/mL (8.12-19.97 interquartile range), 4.96 µg/mL (4.60-6.43) and 137.00 µg/mL (110.5-162.00) in the 10-min protocol, 3-min protocol and drop protocol, respectively. The result for the drop protocol was significantly higher than those of both nebulization protocols in NALF (p = 0.039). In serum, the gentamicin concentration was 0.98 µg/mL (0.65-1.53) and 0.25 µg/mL (0.25-0.44) in the 10-min and 3-min protocols, respectively. Gentamicin was not detected in the serum of seven out of ten dogs in the drop protocol, and gentamicin was significantly higher in the 10-min protocol compared to the drop protocol (p = 0.001). This study found that the 10-min, 3-min and drop protocols achieved superior concentrations in NALF compared to the minimum inhibitory concentration for gentamicin-sensitive bacteria, while remaining below the toxic values in blood.