RESUMEN
Melamine caused acute nephrotoxicity in a past food adulteration incident, but it is unclear whether and how widespread ambient exposure to melamine and related compounds might affect pediatric kidney health. We assessed cross-sectional associations between childhood exposure to melamine and its derivatives and biomarkers of kidney injury and health and explored potential heterogeneity by sex suggested by sex-dependent differences in renal physiology. We measured melamine and its derivatives ammeline, ammelide, and cyanuric acid (CYA) in spot urine samples collected from 192 children from an urban site (Seattle, WA) and 187 children from a rural site (Yakima, WA) aged 4-8 years in the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Study. In addition, biomarkers of kidney injury were measured in the same urine samples, including albumin, total protein, KIM-1, NAG, NGAL, and EGF. We utilized linear regressions to examine associations between individual chemical exposures and kidney biomarkers. Interaction terms examined association modification by sex, as well as potential interactions between melamine and CYA. Despite comparable exposures, girls had higher levels of many kidney injury biomarkers compared to boys. A ten-fold higher melamine concentration was associated with a 18% (95% CI: 5.6%, 31%) higher EGF in the full sample, while ten-fold higher melamine was associated with a 76% (14.1%, 173%) higher KIM-1 in boys but not in girls (-10.1% (-40.6%, 36.1%), interaction p = 0.026). Melamine exhibited significant negative interactions with CYA in association with total protein and NAG that appeared to be specific to girls. Our results suggest possible associations between melamine exposure and markers of kidney injury that may be more pronounced in boys. These findings provide novel insights into melamine and related derivative compound health effects at low levels of exposure in children and emphasize the role of sex in mediating the relationship between nephrotoxicant exposure and kidney injury.
Asunto(s)
Biomarcadores , Exposición a Riesgos Ambientales , Triazinas , Humanos , Triazinas/orina , Triazinas/toxicidad , Femenino , Masculino , Niño , Preescolar , Biomarcadores/orina , Riñón/efectos de los fármacos , Estudios Transversales , Contaminantes Ambientales/orina , Contaminantes Ambientales/toxicidadRESUMEN
Melamine is a high-production-volume chemical and a kidney toxicant. Diet is a key source of melamine exposure, yet little is known about which foods in the US diet may be contaminated. This study evaluated the associations of foods and dietary patterns with melamine exposure using data from 478 US adults and children from the National Health and Nutrition Examination Survey 2003-2004. Melamine concentrations were measured in spot urine samples. Dietary recalls were used to collect dietary data from the day preceding urine collection. Melamine was detectable (>0.09 ng/mL) in 76.2% of the participants' urine. The geometric mean urinary melamine was 11.563 µg/g of creatinine (standard error (SE): 1.235). In adjusted linear regression models, each additional ounce of processed meats or whole grains was associated with 10.6% (95% confidence interval (CI): 2.7, 19.0; p = 0.007) or 17.4% (95% CI: 4.7, 31.7; p = 0.006) greater creatinine-adjusted melamine concentrations, respectively. A dietary pattern characterized by high fruit, whole grain, milk, and yogurt intake was positively associated with melamine exposure. In conclusion, processed meats, whole grains, and possibly other plant-based foods may be important melamine sources in the US. Future research should confirm these findings using more recent data and examine the potential health risks of chronic low-level melamine exposure.
Asunto(s)
Dieta/estadística & datos numéricos , Exposición Dietética/análisis , Triazinas/orina , Adolescente , Adulto , Niño , Creatinina/orina , Dieta/efectos adversos , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Estados Unidos , Adulto JovenRESUMEN
Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and sulfobutylether ß-cyclodextrin sodium (SEBCD). Additional studies may prove informative, particularly in the evaluations of therapeutic options for coronavirus disease 2019 (COVID-19).
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/administración & dosificación , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/terapia , Furanos/orina , Neumonía Viral/terapia , Pirroles/orina , Triazinas/orina , beta-Ciclodextrinas/orina , Adenosina/análogos & derivados , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/química , Adenosina Monofosfato/metabolismo , Alanina/administración & dosificación , Alanina/efectos adversos , Alanina/química , Alanina/metabolismo , Antivirales/efectos adversos , Antivirales/química , Antivirales/metabolismo , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/cirugía , Infecciones por Coronavirus/virología , Interacciones Farmacológicas , Furanos/efectos adversos , Furanos/química , Humanos , Unidades de Cuidados Intensivos , Trasplante de Pulmón , Insuficiencia Multiorgánica , Pandemias , Neumonía Viral/cirugía , Neumonía Viral/virología , Pirroles/efectos adversos , Pirroles/química , Diálisis Renal , SARS-CoV-2 , Receptores de Trasplantes , Triazinas/efectos adversos , Triazinas/química , beta-Ciclodextrinas/efectos adversos , beta-Ciclodextrinas/química , Tratamiento Farmacológico de COVID-19RESUMEN
Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl ß-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 µg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.
Asunto(s)
Calcio , Riñón/efectos de los fármacos , Triazinas/toxicidad , Triazinas/orina , Urolitiasis/orina , Acetilglucosaminidasa/orina , Adulto , Anciano , Teorema de Bayes , Biomarcadores/orina , Exposición a Riesgos Ambientales , Femenino , Humanos , Riñón/fisiopatología , Masculino , Cadenas de Markov , Persona de Mediana Edad , Método de Montecarlo , Probabilidad , Urolitiasis/fisiopatologíaRESUMEN
RATIONALE: Melamine is ubiquitously present in our daily life. It has a known effect on the kidneys, but it may also adversely affect the reproduction system. We have developed an analytical method for measuring melamine levels in maternal placenta and correlated these levels with melamine concentrations in urine, a necessary step in finding out if melamine might cross the placenta and enter the circulation of the fetus. METHODS: We used liquid-liquid extraction, clean up by solid-phase extraction (SPE), and isotope-dilution liquid chromatography/tandem mass spectrometry (LC/MS/MS) to measure melamine in placenta specimens. The results of this method were assessed for linearity, limits of quantitation (LOQs), and intra- and inter-assay precision as well as accuracy, matrix effect, and recovery rate. RESULTS: Calibration curves indicated good linearity (r >0.995) over concentrations ranging from 5 to 500 ng/mL in placenta specimens, intra- and inter-assay precision from 0.89% to 27.07%, and accuracy from 92.4% to123.5%. Recovery ranged from 63.9 to 83.9%, and the LOQ was 5 ng/mL in placenta (0.2 g). Placental melamine levels ranged from 7.87 to19.64 ng/mL, all detectable (n = 8). Pregnant women with higher levels of urinary melamine had higher placenta melamine levels than those with non-detectable urinary melamine, though the results were not significantly different (p = 0.149, n = 4 in each group). CONCLUSIONS: The results of this study suggest that pregnant women were exposed to low doses of melamine in their daily lives as measured in urine samples and placenta specimens. It is unclear whether placenta melamine concentrations can better represent long-term exposure than urine or whether melamine in the uterus can enter the fetus via this route.
Asunto(s)
Placenta/química , Espectrometría de Masas en Tándem/métodos , Triazinas/análisis , Cromatografía Liquida/métodos , Femenino , Humanos , Límite de Detección , Microextracción en Fase Líquida/métodos , Embarazo , Extracción en Fase Sólida/métodos , Triazinas/orinaRESUMEN
BACKGROUND AND OBJECTIVES: CKD is a global public health problem. Some cross-sectional studies have associated environmental melamine exposure with kidney diseases, but evidence is limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted this prospective cohort study to enroll patients with eGFR≥30 ml/min per 1.73 m2 in 2006-2010. Urinary corrected melamine levels (ratio of urinary melamine to urinary creatinine) were measured by liquid chromatography/tandem mass spectrometry at enrollment. Kidney outcomes included doubling of serum creatinine levels, eGFR decline >3 ml/min per 1.73 m2 per year, and 30% decline in eGFR in the first 2 years. Subjects were followed until targeted kidney outcomes, cancer, death, last contact, or the end of observation in December 2016. RESULTS: In a total of 293 subjects, the median urinary corrected melamine level was 0.97 (interquartile range, 0.43-2.08) µg/mmol. Over a median follow-up period of 7.0 years, serum creatinine levels doubled in 80 subjects (27%). Subjects in the highest tertile of urinary melamine level 12.70 µg/mmol) had a 2.30 (95% confidence interval, 1.25 to 4.23; P<0.01) hazard risk for doubling of serum creatinine compared with those in the lowest tertile (0.02-0.58 µg/mmol). Similar significant dose-response results were found in eGFR decline >3 ml/min per 1.73 m2 per year and 30% decline in eGFR in the first 2 years. CONCLUSIONS: Urinary melamine level is significantly associated with kidney function deterioration in patients with early-stage CKD.
Asunto(s)
Insuficiencia Renal Crónica/orina , Triazinas/orina , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Following outbreaks of feed and food adulterations with a melamine and cyanuric acid mixture in 2007 and melamine in 2008 respectively, the kinetics and toxicodynamics of the mixture have been investigated particularly in sensitive species such as the rainbow trout. Tissue concentrations and intensity of the adverse effect, melamine-cyanurate crystal formation in kidney, were reported in similar experimental conditions. Here, a recent PBTK model for rainbow trout has been applied to model the kinetics of both single compounds based on residue levels in tissues. Both PBTK models for the single compounds were combined and a model of crystal formation for the mixture melamine-cyanuric acid was also added to predict the intensity of crystal formation under the assumptions that crystals formed either in urine or in kidney tissue. Modelling the kinetics of melamine and cyanuric acid provided a better understanding and prediction of intensity of crystal formation in case of sequential exposures with varying intensity or co-exposure. This study demonstrates, for the first time, how fish PBTK models can play a key role in the understanding and prediction of toxicokinetics and toxicodynamics of mixtures. This study also illustrates how adverse effects may potentially occur even when the compounds are not administered together as a mixture.
Asunto(s)
Oncorhynchus mykiss/metabolismo , Triazinas/farmacocinética , Triazinas/toxicidad , Animales , Cristalización , Interacciones Farmacológicas , Contaminación de Alimentos/análisis , Riñón/química , Riñón/efectos de los fármacos , Riñón/metabolismo , Modelos Animales , Toxicocinética , Triazinas/administración & dosificación , Triazinas/química , Triazinas/metabolismo , Triazinas/orinaRESUMEN
Melamine is used extensively in household products, such as furniture, dinnerware, and food utensils. Several studies have shown that melamine adversely affects kidney function. Nevertheless, little is known about urinary melamine concentrations, and its temporal variability. In this study, 213 first-morning-void urine samples were collected from 19 volunteers for over a month to assess longitudinal variability in concentrations of melamine and its three structural analogues, i.e., cyanuric acid, ammeline, and ammelide. Target analytes were found in all urine samples at mean concentrations of 3.3, 16, 0.99, and 0.62â¯ng/mL, for melamine, cyanuric acid, ammelide, and ammeline, respectively. Cyanuric acid was the major compound found in all urine samples, accounting for 74-80% of the total concentrations, followed by melamine (12-20%), ammelide (4-6%), and ammeline (2-4%). Gender- and age-related differences in melamine concentrations were observed, although no such pattern was found for cyanuric acid. After adjusting for creatinine, melamine and cyanuric acid concentrations were moderately predictable with inter-day intraclass correlation coefficients (ICCs) in the range of 0.541-0.763. Nevertheless, substantial inter-individual variation in melamine levels existed even after creatinine adjustment, as evidenced by low ICCs (0.008-0.108). Cumulative daily intake of melamine and cyanuric acid was calculated on the basis of urinary concentrations and the mean values were found to be at least 10-fold below the current tolerable daily intake.
Asunto(s)
Triazinas/orina , Adulto , Animales , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Adulto JovenRESUMEN
In this open-label study (NCT02142920), we investigated the distribution, pharmacokinetics, and metabolism of the pan-class-I isoform phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor gedatolisib (PF-05212384), following a single intravenous administration in healthy male subjects. A single, 89-mg, intravenous dose of gedatolisib was associated with a favorable safety profile in the 6 healthy subjects evaluated. Peak plasma concentrations for unchanged gedatolisib and total radioactivity were observed at the end of the 30-minute infusion. The only observed drug-related material in plasma was the parent drug, gedatolisib. Terminal half-life for plasma gedatolisib was â¼37 hours. Following the dose, 66%-73% of drug-related material was recovered in the feces. Metabolism of gedatolisib was trace; only 1 oxidative metabolite, M5, was identified in feces (<1% of total dose). Identification of gedatolisib in feces suggests that biliary and/or intestinal secretion of unchanged parent drug significantly contributes to gedatolisib clearance.
Asunto(s)
Morfolinas/farmacocinética , Inhibidores de Proteínas Quinasas/farmacocinética , Triazinas/farmacocinética , Adulto , Células Cultivadas , Ayuno/metabolismo , Heces/química , Voluntarios Sanos , Hepatocitos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Morfolinas/administración & dosificación , Morfolinas/sangre , Morfolinas/orina , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/sangre , Inhibidores de Proteínas Quinasas/orina , Triazinas/administración & dosificación , Triazinas/sangre , Triazinas/orinaRESUMEN
1. The absorption, distribution, metabolism and excretion of enasidenib were studied following a single oral dose of [14C]enasidenib to rats (10 mg/kg; 100 µCi/kg) and healthy volunteers (100 mg; 318 nCi). 2. Enasidenib was readily absorbed, extensively metabolized and primarily eliminated via the hepatobiliary pathway. Enasidenib-derived radioactivity was widely distributed in rats. Excretion of radioactivity was approximately 95-99% of the dose from rats in 168 h post-dose and 82.4% from human volunteers in 504 h post-dose. In rat bile, approximately 35-42% of the administered dose was recovered, with less than 5% of the dose excreted as the parent drug. Renal elimination was a minor pathway, with <12% of the dose excreted in rat urine and <10% of the dose excreted in human urine. 3. Enasidenib was the prominent radioactive component in rat and human systemic circulation. Enasidenib was extensively metabolized in rats and human volunteers through N-dealkylation, oxidation, direct glucuronidation and combinations of these pathways. Glucuronidation was the major metabolic pathway in rats while N-dealkylation was the prominent metabolic pathway in human volunteers. All human metabolites were detected in rats.
Asunto(s)
Aminopiridinas/farmacocinética , Antineoplásicos/farmacocinética , Triazinas/farmacocinética , Aminopiridinas/sangre , Aminopiridinas/orina , Animales , Antineoplásicos/sangre , Antineoplásicos/orina , Bilis/metabolismo , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Humanos , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Riñón/metabolismo , Hígado/metabolismo , Redes y Vías Metabólicas , Ratas , Espectrometría de Masas en Tándem , Triazinas/sangre , Triazinas/orinaRESUMEN
Swimming pool water ingestion volumes are necessary for assessing infection risk from swimming. Pool water ingestion volumes can be estimated by questionnaire or measuring a chemical tracer in swimmer urine. Questionnaires are often preferred to the chemical tracer method because surveys are less time consuming, but no research exists validating questionnaires accurately quantify pool water ingestion volumes. The objective of this study was to explore if questionnaires are a reliable tool for collecting pool water ingestion volumes. A questionnaire was issued at four pool sites in Tucson, Arizona to 46 swimmers who also submitted a urine sample for analyzing cyanuric acid, a chemical tracer. Perceived ingestion volumes reported on the questionnaire were compared with pool water ingestion volumes, quantified by analyzing cyanuric acid in swimmer urine. Swimmers were asked if they swallowed (1) no water or only a few drops, (2) one to two mouthfuls, (3) three to five mouthfuls, or (4) six to eight mouthfuls. One mouthful is the equivalent of 27 mL of water. The majority (81%) of swimmers ingested <27 mL of pool water but reported ingesting >27 mL ("one mouthful") on the questionnaire. More than half (52%) of swimmers overestimated their ingestion volume. These findings suggest swimmers are over-estimating pool water ingestion because they perceive one mouthful is <27 mL. The questionnaire did not reliably collect pool water ingestion volumes and should be improved for future exposure assessment studies. Images of the ingestion volume categories should be included on the questionnaire to help swimmers visualize the response options.
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Ingestión de Alimentos/fisiología , Encuestas y Cuestionarios/normas , Piscinas/estadística & datos numéricos , Natación , Triazinas/orina , Agua/efectos adversos , Agua/análisis , Adolescente , Adulto , Arizona , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Antipsicóticos/orina , Fenciclidina/orina , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/orina , Triazinas/orina , Adulto , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Ensayos Clínicos como Asunto , Reacciones Falso Positivas , Femenino , Humanos , Inmunoensayo , Lamotrigina , Espectrometría de Masas , Perfenazina/farmacología , Perfenazina/uso terapéutico , Perfenazina/orina , Fenciclidina/farmacología , Triazinas/farmacología , Triazinas/uso terapéuticoRESUMEN
Melamine is a nitrogen-containing organic compound that is used in a wide range of products, including paints, plastics, and paper, as a flame retardant. A few studies have reported the occurrence of melamine and its derivatives in pet food, following a number of deaths of cats and dogs from kidney failure in 2007, which was attributed to melamine contamination in ingredients used in pet food. Nevertheless, studies that report the occurrence of melamine and its derivatives in pet urine are scarce. In this study, we measured melamine and its derivatives (i.e., ammeline, ammelide, and cyanuric acid) in dog (nâ¯=â¯30) and cat (nâ¯=â¯30) urine collected from Albany, New York, USA, during March through July 2017. The mean (±SD) concentrations of melamine, ammeline, ammelide, and cyanuric acid in dog urine were 21.1⯱â¯51.2, 2.3⯱â¯3.8, 9.9⯱â¯1 0.4, and 79.0⯱â¯105â¯ng/mL, respectively; the corresponding concentrations in cats were 21.4⯱â¯26.1, 1.2⯱â¯2.5, 6.1⯱â¯3.9, and 105⯱â¯94.6â¯ng/mL, respectively. No significant difference was observed in urinary concentrations of melamine derivatives between cats and dogs. Age and gender were important determinants of the concentrations of the target chemicals in cats and dogs. Cumulative daily intake of melamine and its derivatives was calculated on the basis of urinary concentrations and was found to be 10-500-fold below the tolerable daily intake.
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Alimentación Animal/análisis , Retardadores de Llama/metabolismo , Contaminación de Alimentos/análisis , Triazinas/orina , Animales , Gatos , Perros , Femenino , Retardadores de Llama/análisis , Contaminación de Alimentos/estadística & datos numéricos , Masculino , New York , NitrógenoRESUMEN
Biological monitoring of occupational exposure to 1,6-hexamethylene diisocyanate (HDI)-containing spray-paints is limited to analysis of metabolites of HDI monomer although polymeric HDI isocyanurate constitutes the predominant inhalation and skin exposure for workers in the automotive paint industry. A novel method using nanoflow ultra-performance liquid chromatography coupled to nano-electrospray ionization tandem mass spectrometry (nano-UPLC-ESI-MS/MS) was developed to quantify trisaminohexyl isocyanurate (TAHI), a hydrolysis product of HDI isocyanurate, in the urine of spray-painters. Analytical and internal standards were synthesized in-house and weighted linear regression calibration curves were generated using spiked control urine from non-exposed persons (0.06-7.98⯵g/L; Nâ¯=â¯13; wâ¯=â¯x-2; râ¯=â¯0.998). Urine samples collected from 15 exposed workers (Nâ¯=â¯111) were subjected to acid hydrolysis and extracted with dichloromethane, then derivatized with acetic anhydride. The derivatized product, trisacetamidohexyl isocyanurate (TAAHI), was analyzed using nano-UPLC-ESI-MS/MS. The protocol was sensitive and specific for analysis of TAHI in the urine of exposed workers with a method detection limit at 0.03⯵g/L. TAHI was detected in 33 of 111 urine samples and in 11 of 15 workers. This biomarker for HDI isocyanurate is critical to determine the relative potency and dose-relationships between the monomer and oligomer exposure on the development of diisocyanate induced health effects in future studies.
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Isocianatos/toxicidad , Exposición Profesional/análisis , Triazinas/orina , Biomarcadores/química , Biomarcadores/orina , Cromatografía Líquida de Alta Presión , Humanos , Masculino , Nanotecnología , Pintura , Espectrometría de Masas en Tándem , Triazinas/químicaRESUMEN
Environmental low-dose melamine exposure has been associated with urolithiasis risk in adults, but it is unclear if this exposure can cause early renal damage. This cross-sectional study investigated the association of this exposure and early renal damage in patients with calcium urolithiasis. We recruited patients diagnosed with upper urinary tract calcium urolithiasis from three hospitals in southwestern Taiwan between November 2010 and January 2015. All patients completed a structured questionnaire and provided one-spot urine samples for the measurement of melamine level and markers of early renal injury, including N-acetyl b-d-glucosaminidase (NAG), ß2-microglobulin (ß2-MG), and microalbumin. We used urinary melamine levels as an indicator of environmental melamine exposure. A total of 309 patients (mean age of 54.7 ± 12.8 years) were studied. Median urinary melamine level (µg/mmol Cr) was 1.26 (interquartile range 0.48-3.29). A significant and positive correlation was found between urinary melamine concentration and urinary NAG levels (Spearman correlation coefficient, r = 0.157, p = 0.006, n = 309). With urinary melamine levels categorized into quartiles, multivariate regression results showed the same relationship, particularly in those with first stone episode. In this group, patients with the highest quartile of urinary melamine concentration had a 3.95-fold risk (95% confidence interval = 1.43-10.94) of high NAG levels (dichotomized by median), compared to the lowest quartile after adjustment. No association was found between urinary melamine concentration and urinary microalbumin levels. In conclusion, urinary melamine is significantly associated with urinary marker of early renal tubular injury, NAG, in urolithiasis patients, especially ones with first stone episode.
Asunto(s)
Contaminantes Ambientales/orina , Túbulos Renales/lesiones , Triazinas/orina , Urolitiasis/orina , Acetilglucosaminidasa , Adulto , Anciano , Biomarcadores/orina , Calcio , Estudios Transversales , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Humanos , Riñón , Masculino , Persona de Mediana Edad , Riesgo , Taiwán , Urolitiasis/epidemiologíaRESUMEN
The use of cyanuric acid as a biomarker for ingestion of swimming pool water may lead to quantitative knowledge of the volume of water ingested during swimming, contributing to a better understanding of disease resulting from ingestion of environmental contaminants. When swimming pool water containing chlorinated cyanurates is inadvertently ingested, cyanuric acid is excreted quantitatively within 24 h as a urinary biomarker of ingestion. Because the volume of water ingested can be quantitatively estimated by calculation from the concentration of cyanuric acid in 24 h urine samples, a procedure for preservation, cleanup, and analysis of cyanuric acid was developed to meet the logistical demands of large scale studies. From a practical stand point, urine collected from swimmers cannot be analyzed immediately, given requirements of sample collection, shipping, handling, etc. Thus, to maintain quality control to allow confidence in the results, it is necessary to preserve the samples in a manner that ensures as quantitative analysis as possible. The preservation and clean-up of cyanuric acid in urine is complicated because typical approaches often are incompatible with the keto-enol tautomerization of cyanuric acid, interfering with cyanuric acid sample preparation, chromatography, and detection. Therefore, this paper presents a novel integration of sample preservation, clean-up, chromatography, and detection to determine cyanuric acid in 24 h urine samples. Fortification of urine with cyanuric acid (0.3-3.0 mg/L) demonstrated accuracy (86-93% recovery) and high reproducibility (RSD < 7%). Holding time studies in unpreserved urine suggested sufficient cyanuric acid stability for sample collection procedures, while longer holding times suggested instability of the unpreserved urine. Preserved urine exhibited a loss of around 0.5% after 22 days at refrigerated storage conditions of 4 °C.
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Biomarcadores/orina , Piscinas , Triazinas/orina , Agua/química , Ingestión de Alimentos , Humanos , Reproducibilidad de los Resultados , NataciónRESUMEN
Terbuthylazine is a selective pre- and post-emergency chloro-triazine herbicide used for a broad spectrum of weed control. We evaluated the potential of low doses of terbuthylazine to induce oxidative stress and cytogenetic damage in peripheral blood samples of adult male Wistar rats. Following 28-day repeated oral exposure at 0.004 mg/kg b.w./day, 0.4 mg/kg b.w./day and 2.29 mg/kg b.w./day, parameters of lipid peroxidation, total antioxidant capacity, and activities of antioxidant enzymes were measured in blood samples. Alkaline comet assay on leukocytes and erythrocyte micronucleus assay were used to measure DNA damage. In addition, the concentration of terbuthylazine and its metabolite in urine and plasma were determined using high performance liquid chromatography with UV diode-array detector (HPLC-UV-DAD). The fraction of terbuthylazine excreted in urine was negligible and was not found in plasma. Deethylterbuthylazine was only compound detected in plasma samples. Exposure to terbuthylazine did not induce significant lipid peroxidation products. The significant changes in antioxidant enzyme activities and the elevated total antioxidant capacity indicated that terbuthylazine at experimental conditions applied has potential to disturb oxidative/antioxidant balance. Results regarding the alkaline comet assay as well as micronucleated reticulocyte frequency indicated that treatment led to low-level DNA instability. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios.
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Daño del ADN/efectos de los fármacos , Herbicidas/metabolismo , Herbicidas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Triazinas/metabolismo , Triazinas/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Contaminantes Ambientales/sangre , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Herbicidas/sangre , Peroxidación de Lípido , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Triazinas/sangre , Triazinas/orinaRESUMEN
The volume of water ingested by swimmers while swimming is of great interest to individuals who develop risk assessments using quantitative microbial risk assessment or epidemiological approaches. We have used chloroisocyanurate disinfected swimming pool waters to determine the amount of water swallowed by swimmers during swimming activity. The chloroisocyanurate, which is in equilibrium with chlorine and cyanuric acid in the pool water, provides a biomarker, cyanuric acid, that once swallowed passes through the body into the urine unchanged. The concentration of cyanuric acid in a 24 hour urine specimen and the concentration in pool water can be used to calculate the amount of water swallowed. Our study population of 549 participants, which was about evenly divided by gender, and young and adult swimmers, indicated that swimmers ingest about 32 mL per hour (arithmetic mean) and that children swallowed about four times as much water as adults during swimming activities. It was also observed that males had a tendency to swallow more water than females during swimming activity and that children spent about twice as much time in the water than adults.
Asunto(s)
Desinfectantes/metabolismo , Ingestión de Líquidos , Exposición a Riesgos Ambientales , Piscinas , Triazinas/orina , Agua/análisis , Adolescente , Adulto , Factores de Edad , Anciano , Biomarcadores/orina , Cloro/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ohio , Factores Sexuales , Natación , Triazinas/metabolismo , Adulto JovenRESUMEN
AIM: Fotagliptin is a novel dipeptidyl peptidase IV inhibitor under clinical development for the treatment of Type II diabetes mellitus. The objective of this study was to develop and validate a specific and sensitive ultra-performance liquid chromatography (UPLC)-MS/MS method for simultaneous determination of fotagliptin and its two major metabolites in human plasma and urine. Methodology & results: After being pretreated using an automatized procedure, the plasma and urine samples were separated and detected using a UPLC-ESI-MS/MS method, which was validated following the international guidelines. CONCLUSION: A selective and sensitive UPLC-MS/MS method was first developed and validated for quantifying fotagliptin and its metabolite in human plasma and urine. The method was successfully applied to support the clinical study of fotagliptin in Chinese healthy subjects.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Dipeptidil Peptidasa 4/química , Piperidinas/sangre , Piperidinas/orina , Inhibidores de Proteasas/sangre , Inhibidores de Proteasas/orina , Espectrometría de Masas en Tándem/métodos , Triazinas/sangre , Triazinas/orina , Automatización , Calibración , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/orina , Humanos , Modelos Lineales , Control de Calidad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The melamine contaminated milk powder contamination scandal occurred in China in 2008. Its main consequences so far have been urinary stone formation in children with associated renal damage and increased child mortality. Eight years have passed, but food safety issues still remain of concern in the daily lives of millions of Chinese. Vigilance is required to ensure no recurrence of such food safety problems. Ongoing studies focus on the early detection of food industry malpractice, mechanisms whereby these toxic substances induce disease and how its advent may be prevented and better managed. Melamine undergoes renal excretion, but is metabolized slowly and excreted largely unchanged in the urine. Urinary melamine measurement may provide a rapid and inexpensive way to identify exposure to melamine adulterated food items. Although most patients with melaminerelated urinary stones (MUS) have been responsive to conservative treatment, longer time follow-up is needed to assess chronic effects. Aside from MUS, melamine is a recognized carcinogen and can induce urinary tract tumours. Very little is known about the effects of excessive exposure to melamine contaminated milk powder in infants on growth, adolescent and adult health, although short-term effects have become apparent during the scandal.