ABSTRACT
Extracorporeal photopheresis is an established procedure for refractory graft-versus-host disease, a major complication associated with notable morbidity and mortality in patients with allogeneic hematopoietic stem cell transplant. Despite being implemented over a decade ago, there is scant information about potential interactions or analytical interferences with concomitant drugs in this polymedicated population. Here we report the case of a pediatric patient diagnosed with cutaneous steroid-refractory acute graft-versus-host disease after unrelated allogeneic hematopoietic stem cell transplant that was treated with photopheresis. Analytical quantification of voriconazole by HPLC-PDA the day following photopheresis treatment did not permit therapeutic drug monitoring (TDM) due to the presence of interference at the voriconazole retention time. Following investigations, it was demonstrated that the interference is likely attributable to a psoralen-based compound. The interference was not present when samples were obtained prior to photopheresis, enabling TDM. This case underscores the relevance of communication among the members of the treating team to perform reliable TDM, especially in routine clinical practice of pediatric patients with complex diseases undergoing innovative treatments. This finding is relevant to voriconazole quantification by HPLC-PDA, frequently used in laboratories based in middle-income countries.
ABSTRACT
Differences in the As methylation capacity of Argentine children, exposed to different levels of As in drinking water were evaluated, considering the gender and the presence of the As3MT T860C gene polymorphism. Inorganic As (%IAs), monomethylated As (%MMA) and dimethylated As (%DMA), primary methylation index (PMI) and secondary methylation index (SMI) were evaluated and represented the As methylation capacity. Urinary As ranged from 18 to 5106 µg/g creatinine. Comparisons were performed between lowest and highest quartiles of urinary As. The level of exposure was positively related to urinary %MMA and negatively to %DMA and to SMI. Considering the presence of the As3MT T860C polymorphism, the level of exposure increased %MMA, and decreased %DMA and the SMI in carriers of the T/T genotype. SMI OR for T/T carriers was 10.61 (95% CI: 2.16-52.16, p: 0.0036). Regarding the gender, the level of exposure increased %MMA, and decreased %DMA and the SMI in girls and boys. SMI OR for girls was 8.71 (95% CI: 1.48-51.08, p: 0.0165) and for boys, OR: 18.15 (95% CI: 2.03-162.35, p: 0.0095). It was possible to identify the level of exposure as a factor that can modify the influence that other factors have on the methylation of As.
Subject(s)
Arsenic , Arsenicals , Drinking Water , Arsenic/toxicity , Child , Drinking Water/analysis , Environmental Exposure/analysis , Female , Genotype , Humans , Male , Methylation , Methyltransferases/geneticsABSTRACT
Introducción: la exposición crónica al benceno y tolueno produce alteraciones sobre la médula ósea y el sistema nervioso central, entre otros. En orina, el ácido trans, trans mucónico (t, t-MA) es uno de los biomarcadores de exposición al benceno y el o-cresol (oCre) al tolueno. Objetivo: analizar los resultados de los niveles de t, t-MA y oCre urinarios en una población infanto-juvenil residente en Ciudad Autónoma de Buenos Aires y Conurbano Bonaerense potencialmente expuesta a benceno y tolueno ambiental. Materiales y métodos: se realizó un estudio retrospectivo de los resultados de t, t-MA y oCre urinarios. Las muestras de orina ingresaron al laboratorio con solicitud de t, t-MA (n=1519) y oCre (n=1447) durante el período 2011-2017 (rango etario entre 0 a 19 años). El t, t-MA se cuantificó por UFLC con detector de arreglo de diodos y el oCre por CG con detector de ionización por llama. Resultados: la edad promedio de los pacientes fue de 4,8 años y la mediana 4,6 años.Las concentraciones de t, t-MA urinario fueron: menor de 50 μg/l (44,8%); entre 50-500 μg/l (52,1%) y mayores de 500 μg/l (3,1%). Expresadas por gramo de creatinina: entre 15-163 μg/g creatinina (60,4%) y mayores de 163 μg/g creatinina (39,6%). El límite de cuantificación de t, t-MA fue de 50 μg/l. Las concentraciones de oCre urinario fueron: menor de 0,20 mg/l (97,7%) y entre 0,20-0,50 mg/l (2,3%) y mayor de 0,50 mg/l (0%). Expresadas por gramo de creatinina: menor de 0,30 mg/g creatinina en el 0,8% y mayores de 0,30 mg/g creatinina en el 1,5%. El límite de cuantificación de oCre fue de 0,20 mg/l. Conclusiones: los resultados del trabajo podrían indicar una contaminación ambiental persistente, en especial en el Conurbano Bonaerense, donde debería continuarse el monitoreo de algunas zonas. Pero, por otro lado, es de vital importancia tener en cuenta los factores de confusión, tales como la dieta, la exposición al humo de tabaco ambiental (fumador pasivo) y la tasa de excreción renal que llevarían a una sobre-estimación de los resultados y a una incorrecta toma de decisiones.
Introduction: Chronic exposure to benzene and toluene produces alterations in the bone marrow and the central nervous system, among other effects. In urine, trans, trans muconic acid (t, t-MA) is one of the biomarkers of exposure to benzene and o-cresol (oCre), to toluene. Objective: To analyze the results of urinary t, t-MA and oCre levels in an infant-juvenile population resident in the Autonomous City of Buenos Aires and the Conurbano Bonaerense, potentially exposed to environmental benzene and toluene. Materials and methods: A retrospective study of urinary t, t-MA and oCre results was performed. The urine samples entered the laboratory with the request of t, t-MA (n = 1519) and oCre (n = 1447) during the period 2011- 2017. The age range of the population was between 0 and 19 years. The t, t-MA was quantified by UFLC with diode array detector and the oCre by GC with flame ionization detector. Results: The average age of the patients was 4.8 years and the median age was 4.6 years. The urinary concentrations of t, t-MA were: below 50 μg/l (44.8%); between 50-500 μg/l (52.1%) and above 500 μg/l (3.1%). Expressed per gram of creatinine: between 15-163 μg/g creatinine (60.4%) and greater 163 μg/g creatinine (39.6%). The limit of quantification of t, t-MA was 50 μg/l. The urinary oCre concentrations were: less than 0.20 mg/l (97.7%) and between 0.20-0.50 mg/l (2.3%). Expressed per gram of creatinine: less than 0.30 mg/g creatinine in 0.8% and greater than 0.30 mg/g creatinine in 1.5%. The limit of quantification of oCre was 0.20mg/l. Conclusions: The results of the study could indicate persistent environmental contamination, especially in the Conurbano Bonaerense, where monitoring of some areas should be continued. However, it is of vital importance to take into account the confounding factors, such as diet, exposure to environmental tobacco smoke (passive smoking) and the rate of renal excretion, which would lead to an over-estimation of the results and to incorrect decision-making.
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Toluene/poisoning , Toluene/urine , Benzene/poisoning , Biomarkers/analysis , Biomarkers/urine , Argentina/epidemiology , Urban Area , Chemical Compound Exposure , Inhalation Exposure/adverse effects , Environmental Pollution/adverse effectsABSTRACT
Numerosos datos clínicos y experimentales han demostrado que la nicotina del tabaco (NI) es la razón de la adicción al tabaco en los seres humanos, a través de la inducción de la tolerancia y la dependencia física. El humo del tabaco contiene otros alcaloides que pueden contribuir a la adicción, como la cotinina (COT). En este estudio se evaluaron los posibles efectos de la COT en ratas durante el síndrome de abstinencia nicotínica midiendo la actividad locomotora espontánea (ALE) utilizando el test del campo abierto. El estudio se llevó a cabo con dos grupos de ratas que recibieron NI 10 mg / kg / día en agua potable durante 120 días (grupos A y B). Luego, en el grupo A, se sustituyó NI por agua potable y en el grupo B, sustituido por COT 12 mg / kg, durante 24 horas en ambos grupos. La actividad locomotora espontánea se registró al final del día 120 (nivel basal) y al final del día 121, al final del período de abstinencia. Los resultados obtenidos se compararon con las mediciones basales. El grupo A mostró diferencias significativas en 3 de los 9 movimientos medidos y el grupo B mostró diferencias significativas en 7 de los 9 movimientos medidos. Cuando el grupo A se comparó con el grupo B sólo 1 movimiento mostró diferencia significativa. Estos resultados sugieren que en la administración crónica de nicotina y en estas condiciones experimentales, la cotinina participa en el síndrome de abstinencia nicotínica
A large amount of clinical and experimental data has shown that tobacco nicotine (NI) is the reason for tobacco addiction in humans, through the induction of tolerance and physical dependence. Tobacco smoke contains other alkaloids that may contribute to addiction, such as cotinine (COT). In this study we evaluated the possible effects of COT in rats during NI abstinence syndrome by measuring spontaneous locomotor activity (SLA) with an open field test. The study was carried out with two groups of rats receiving NI 10 mg / kg / day in drinking water for 120 days (groups A and B). Then, in group A, NI was replaced by drinking water and in group B, substituted by COT, 12 mg / kg, for 24 hours in both groups. Spontaneous locomotor activity was recorded at the end of day 120 (baseline) and at the end of day 121, the end of the abstinence period. The results obtained were compared against the baseline measurements and group A showed significant differences in 3 of the 9 movements measured and group B displayed significant differences in 7 of the 9 movements measured. When group A was compared with Group B only 1 movement showed any significant differences. These results suggest that cotinine participates in the nicotine withdrawal syndrome in chronic nicotine administration under these experimental conditions
