RESUMO
Glycol ethers are an oxygenated solvent family widely present in consumer products. Some of them are recognized reproductive, developmental or hematological toxicants. Although several glycol ether biomonitoring studies have been performed on adults from working or general populations, no studies have hitherto been carried out on children. The aim of our study was to explore the detection of glycol ether metabolites in the urinary samples of 6-year-old children, and if any were found, to describe them. The PELAGIE mother-child cohort included 3421 pregnant women from the general population of Brittany, France, between 2002 and 2006. Our biomonitoring study included a random sample of 110 children from the PELAGIE cohort who had participated in a neurodevelopment evaluation at the age of six. First morning voids were collected from all of the children. Eight urinary glycol ether metabolites were measured using gas chromatography with mass spectrometry. The limit of detection was 0.003 mg/L for all metabolites. Glycol ether metabolites were detected at rates varying from 33.5% of samples for propoxyacetic acid to 100% of samples for phenoxyacetic acid and methoxyacetic acid. The highest median concentration observed was for phenoxyacetic acid (0.141 mg/l). Our study reported the ubiquitous presence of glycol ether metabolites in children's urinary samples. These results call for larger biomonitoring surveys of the general population and study of the potential sources and determinants of these exposures.
Assuntos
Poluentes Ambientais/urina , Éteres/urina , Glicóis/urina , Monitoramento Biológico , Criança , Feminino , França , Humanos , MasculinoRESUMO
BACKGROUND: Pregnant women are ubiquitously exposed to organic solvents, such as glycol ethers. Several studies suggest potential developmental neurotoxicity following exposure to glycol ethers with a lack of clarity of possible brain mechanisms. OBJECTIVES: We investigated the association between urinary levels of glycol ethers of women during early pregnancy and motor inhibition function of their 10- to 12-year-old children by behavioral assessment and brain imaging. METHODS: Exposure to glycol ethers was assessed by measuring six metabolites in urine (<19â¯weeks of gestation) of 73 pregnant women of the PELAGIE mother-child cohort (France). Maternal urinary levels were classified as low, medium, or high. Children underwent functional magnetic resonance imaging (fMRI) examinations during which motor inhibition function was assessed with a Go/No-Go task. Analyses were performed using linear regression for task performance and generalized linear mixed-effect models for brain activation, FWER-corrected for multiple testing at the spatial cluster level. Confounders were considered by restriction and a priori adjustment. RESULTS: Higher maternal butoxyacetic acid (BAA) urinary concentrations were associated with poorer child performance (ßâ¯=â¯-1.1; 95% CI: -1.9, -0.2 for high vs low). There was also a trend for ethoxyacetic acid (EAA) towards poorer performance (ßâ¯=â¯-0.3; 95% CI: -0.7, 0.01). Considering inhibition demand, there were increased activity in occipital regions in association with moderate EAA (left cuneus) and moderate methoxyacetic acid (MAA) (right precuneus). When children succeeded to inhibit, high ethoxyethoxyacetic acid (EEAA) and moderate phenoxyacetic acid (PhAA) levels were associated with differential activity in frontal cortex, involved in inhibition network. DISCUSSION: Prenatal urinary levels of two glycol ether metabolites were associated with poorer Go/No-Go task performance. Differential activations were observed in the brain motor inhibition network in relation with successful inhibition, but not with cognitive demand. Nevertheless, there is no consistence between performance indicators and cerebral activity results. Other studies are highly necessary given the ubiquity of glycol ether exposure.
Assuntos
Poluentes Ambientais/toxicidade , Éteres/urina , Glicóis/urina , Exposição Materna , Atividade Motora , Efeitos Tardios da Exposição Pré-Natal , Acetatos/urina , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Criança , Estudos de Coortes , Feminino , França , Humanos , Imageamento por Ressonância Magnética , Masculino , Gravidez , SolventesRESUMO
BACKGROUND: Glycol ethers (GE) are widely used organic solvents. Despite the potential neurotoxicity of several families of organic solvents, little is known about the impact of GE on the neurodevelopment of infants and children. OBJECTIVES: We investigated the relation between urinary concentrations of GE metabolites in pregnant women and neurocognitive abilities in their 6-year-old children in the PELAGIE mother-child cohort. METHODS: Five GE metabolites were measured in first morning void urine samples of 204 French pregnant women in early pregnancy (< 19 weeks of gestation). Psychologists assessed the neurocognitive abilities of their 6-year-old children with the Wechsler Intelligence Scale for Children IV (WISC) and the Developmental Neuropsychological Assessment (NEPSY). We analyzed the results with linear (WISC) and Poisson regression models (NEPSY), adjusted for potential confounders, including child's stimulation at home. RESULTS: GE metabolites were detected in 90-100% of maternal urine samples. The WISC Verbal Comprehension score was significantly lower for children with the highest tertile of urinary phenoxyacetic acid (PhAA) [ß (third vs. first tertile) = -6.53; 95% CI: -11.44, -1.62]. Similarly, the NEPSY Design Copying subtest score was lower in those with the highest tertile of urinary ethoxyacetic acid (EAA) [ß (third vs. first tertile) = -0.11; 95% CI: -0.21, 0.00]. The other GE metabolites we studied were not significantly associated with WISC or NEPSY scores. CONCLUSIONS: Prenatal urine concentrations of two GE metabolites were associated with lower WISC Verbal Comprehension Index scores and NEPSY Design Copying subscale scores, respectively, at age 6 years. PhAA is the primary metabolite of 2-phenoxyethanol (EGPhE), which is commonly found in cosmetics, and precursors of EAA are frequently used in cleaning agents. Additional research is needed to confirm our findings and further explore potential effects of prenatal GE exposures on neurocognitive performance in children.
Assuntos
Substâncias Perigosas/toxicidade , Exposição Materna/estatística & dados numéricos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Solventes/toxicidade , Criança , Éteres/toxicidade , Éteres/urina , Etilenoglicóis/metabolismo , Feminino , França/epidemiologia , Glicóis/toxicidade , Glicóis/urina , Substâncias Perigosas/urina , Humanos , Testes de Inteligência , Masculino , Testes Neuropsicológicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/urina , Solventes/metabolismo , Escalas de WechslerRESUMO
Exposure to bisphenol A (BPA), an environmental contaminant, has been linked to metabolic disorders. However, there are no reports describing the effects of BPA on the profiling of cis-diol metabolites. It is challenge to detect these metabolites in biological samples because of their low abundance, high polarity and serious matrix interference. In this study, a chemical isotope-labeling method was applied to solve these problems. Acetone and deuterated acetone (acetone-d6) were used as chemical tags to label the rat urine samples, respectively. The light and heavy labeling products were recognized using the ShiftedIonsFinder software. The selected cis-diol metabolite signals were used to build a data set. The data set was applied to evaluate the changes in the urinary profiling of cis-diol-containing metabolites in rats with BPA exposure. The results showed that chromatographic separation and mass spectrometry detection of cis-diol metabolites were improved after acetone labeling. Using this method, the cis-diol metabolites were recognized easily from the urine samples. By comparing different dose administration on rats, the influence of BPA exposure on cis-diol metabolites was investigated. The analytes showing noticeable differences were identified. It was found that high-dose BPA exposure had strong effects on the cis-diol compound metabolism. The influences were mostly related to the metabolism of galactose and nucleoside and its analogues. The disturbance of the galactose metabolism by BPA is reported for the first time, to the best of our knowledge. This may have some implications for exploring the toxic effects of BPA exposure.
Assuntos
Compostos Benzidrílicos/farmacologia , Glicóis/metabolismo , Glicóis/urina , Metabolômica/métodos , Fenóis/farmacologia , Espectrometria de Massas em Tandem , Urinálise/métodos , Acetona/química , Animais , Cromatografia Líquida , Deutério/química , Feminino , Glicóis/química , Marcação por Isótopo , Ratos , Ratos Sprague-DawleyRESUMO
Glycol ethers are a widely used class of solvents that may lead to both workplace and general population exposures. Biomonitoring studies are available that have quantified glycol ethers or their metabolites in blood and/or urine amongst exposed populations. These biomonitoring levels indicate exposures to the glycol ethers, but do not by themselves indicate a health hazard risk. Biomonitoring Equivalents (BEs) have been created to provide the ability to interpret human biomonitoring data in a public health risk context. The BE is defined as the concentration of a chemical or metabolite in a biological fluid (blood or urine) that is consistent with exposures at a regulatory derived safe exposure limit, such as a tolerable daily intake (TDI). In this exercise, we derived BEs for general population exposures for selected E- and P-series glycol ethers based on their respective derived no effect levels (DNELs). Selected DNELs have been derived as part of respective Registration, Evaluation, Authorisation and Regulation of Chemicals (REACh) regulation dossiers in the EU. The BEs derived here are unique in the sense that they are the first BEs derived for urinary excretion of compounds following inhalation exposures. The urinary mass excretion fractions (Fue) of the acetic acid metabolites for the E-series GEs range from approximately 0.2 to 0.7. The Fues for the excretion of the parent P-series GEs range from approximately 0.1 to 0.2, with the exception of propylene glycol methyl ether and its acetate (Fue = 0.004). Despite the narrow range of Fues, the BEs exhibit a larger range, resulting from the larger range in DNELs across GEs. The BEs derived here can be used to interpret human biomonitoring data for inhalation exposures to GEs amongst the general population.
Assuntos
Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Poluentes Ambientais/metabolismo , Éteres/metabolismo , Glicóis/metabolismo , Substâncias Perigosas/metabolismo , Solventes , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Éteres/sangue , Éteres/urina , Glicóis/sangue , Glicóis/urina , Substâncias Perigosas/sangue , Substâncias Perigosas/urina , Humanos , Nível de Efeito Adverso não Observado , Saúde Pública , Valores de ReferênciaRESUMO
Methods developed for use in emergency toxicology have to be fast and simple. Additionally, such methods should be multi-analyte procedures because they allow monitoring of analytes of different drug classes in one single body sample. This is important because often only a limited amount of sample is available and the results have to be reported as fast as possible. Therefore, we describe the improvement of an existing method published by van Hee at al. The new method is fast and simple and designed for the simultaneous determination of ethylene glycol, 1,2-propylene glycol, lactic acid, glycolic acid, gamma-hydroxybutyric acid (GHB), diethylene glycol, triethylene glycol, and tetraethylene glycol in human plasma or urine. A 50-µL aliquot of sample was deproteinized and 20 µl of the diluted specimen were derivatized using bis-N,O-trimethylsilyl trifluoroacetamide and the catalyst dimethylformamide. After microwave-assisted derivatization, an aliquot was injected into the gas chromatograph and analyzed with electron ionization mass spectrometry in selective ion monitoring mode. All compounds are separated within 12 min and detected with a limit of quantification of 0.05 and 0.01 g/L for glycols and GHB, respectively. Calibration was linear from 0.05 to 1.0 g/L for glycols and 0.01 to 0.2 g/L for GHB. Validation criteria were shown to be in the required limits with exception of lactic acid. Average analysis time from starting sample preparation until quantitative plasma results of approximately 35 min was achieved. This turnaround time is considered most appropriate for emergency cases.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Glicóis/sangue , Glicóis/urina , Hidroxibutiratos/sangue , Hidroxibutiratos/urina , Toxicologia/métodos , Cromatografia Gasosa-Espectrometria de Massas/economia , Glicóis/toxicidade , Humanos , Hidroxibutiratos/toxicidade , Toxicologia/economiaRESUMO
Studies were performed to determine if the detoxification pathway of 1,3-butadiene (BD) through 3-butene-1,2-diol (BD-diol) is a major contributor to mutagenicity in BD-exposed mice and rats. First, female and male mice and rats (4-5 weeks old) were exposed by nose-only for 6h to 0, 62.5, 200, 625, or 1250 ppm BD or to 0, 6, 18, 24, or 36 ppm BD-diol primarily to establish BD and BD-diol exposure concentrations that yielded similar plasma levels of BD-diol, and then animals were exposed in inhalation chambers for 4 weeks to BD-diol to determine the mutagenic potency estimates for the same exposure levels and to compare these estimates to those reported for BD-exposed female mice and rats where comparable blood levels of BD-diol were achieved. Measurements of plasma levels of BD-diol (via GC/MS methodology) showed that (i) BD-diol accumulated in a sub-linear fashion during single 6-h exposures to >200 ppm BD; (ii) BD-diol accumulated in a linear fashion during single or repeated exposures to 6-18 ppm BD and then in a sub-linear fashion with increasing levels of BD-diol exposure; and (iii) exposures of mice and rats to 18 ppm BD-diol were equivalent to those produced by 200 ppm BD exposures (with exposures to 36 ppm BD-diol yielding plasma levels approximately 25% of those produced by 625 ppm BD exposures). Measurements of Hprt mutant frequencies (via the T cell cloning assay) showed that repeated exposures to 18 and 36 ppm BD-diol were significantly mutagenic in mice and rats. The resulting data indicated that BD-diol derived metabolites (especially, 1,2-dihydroxy-3,4-epoxybutane) have a narrow range of mutagenic effects confined to high-level BD (>or=200 ppm) exposures, and are responsible for nearly all of the mutagenic response in the rat and for a substantial portion of the mutagenic response in the mouse following high-level BD exposures.
Assuntos
Compostos de Epóxi/sangue , Compostos de Epóxi/urina , Glicóis/sangue , Glicóis/toxicidade , Glicóis/urina , Hipoxantina Fosforribosiltransferase/genética , Exposição por Inalação , Mutação/genética , Animais , Butadienos/toxicidade , Relação Dose-Resposta a Droga , Feminino , Hemoglobinas/metabolismo , Masculino , Camundongos , Ratos , Ratos Endogâmicos F344 , Reprodutibilidade dos Testes , Baço/citologia , Baço/efeitos dos fármacos , Baço/enzimologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/enzimologia , Fatores de TempoRESUMO
The paper presents the results of assessment of the biological age of workers who are in contact with organic compounds. Analysis of the findings has indicated that there is a relationship between the level of free radical oxidation and the cytotoxic properties of substances. The damaging effect of chemical agents on the workers appeared as higher parameters of biological age.
Assuntos
Envelhecimento , Indústria Química , Glicóis/efeitos adversos , Adulto , Fatores Etários , Glicóis/urina , Humanos , Pessoa de Meia-Idade , Doenças Profissionais/urinaRESUMO
1,3-Butadiene is an important industrial chemical and a common environmental contaminant. Because of its suspected carcinogenicity butadiene-related research has gained high activity. The obvious lack of knowledge so far has been that a biomonitoring method that can detect at least one of the metabolites of butadiene from body fluids or excretas does not exist. In this communication we describe a robust and simple analytical method which can be applied for biomonitoring purposes. We have developed a method that can detect 3-butene-1,2-diol in urine samples of rats inhalation-exposed to various concentrations of 1,3-butadiene. The method is based on liquid-liquid extraction and subsequent gas chromatographic analysis. The extraction efficiency of 3-butene-1,2-diol at a concentration of 2.2 microg/ml was 95% (SD=+/-3%, n=3) and was achieved by using sodium chloride saturation and isopropanol as an extracting solvent. The standard deviation of the gas chromatographic analysis was +/-2% (n=12), the limit of detection was 0.08 microg/ml, the limit of quantitation was 0.11 microg/ml (SD=+/-4.8%, n=3) and the analysis was observed to be linear from 0.11 to 486 microg/ml (R=0.9987). Animals exposed to 1,3-butadiene showed a linear excretion of 3-butene-1,2-diol into urine as a function of butadiene exposure. During the exposure saturation of metabolism or accumulation of 1,3-butadiene or 3-butene-1,2-diol into the body was not observed in any exposure levels used.
Assuntos
Butadienos/toxicidade , Cromatografia Gasosa/métodos , Glicóis/urina , Animais , Relação Dose-Resposta a Droga , Exposição Ambiental , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
3-Butene-1,2-diol (BDD), a metabolite of 1,3-butadiene, is rapidly metabolized by B6C3F1 mice at doses ranging from 10 to 250 mg/kg. Calculation of plasma clearance suggested that the kinetics of BDD metabolism were dose-dependent. Clearance varied 5-fold in this dose range. Urinary excretion of BDD was also dose-dependent but did not exceed 5% of the administered dose. A small fraction of the dose (<1%) was excreted as glucuronide or sulfate conjugates. Benzylimidazole, a cytochrome P450 inhibitor, decreased the clearance of BDD (25 mg/kg) by 44%, whereas 4-methylpyrazole, an alcohol dehydrogenase and cytochrome P450 inhibitor, decreased BDD clearance by 82%. BDD administration (250 mg/kg) resulted in depletion of hepatic and renal nonprotein thiols, by 48 and 22%, respectively. Pretreatment of mice with 4-methylpyrazole provided partial protection against depletion of nonprotein thiols, whereas pretreatment with benzylimidazole was ineffective. Incubation of BDD with NADPH and mouse liver microsomes resulted in time-dependent inactivation of p-nitrophenol hydroxylase (PNPH) activity, a marker for cytochrome P450. Inclusion of glutathione, with or without glutathione peroxidase, did not attenuate the inactivation of PNPH, whereas deferoxamine, superoxide dismutase, catalase, and mannitol provided modest protection. These results are consistent with suicide inhibition of PNPH by BDD, with a minor role for reactive oxygen species in the loss of PNPH. Treatment of mice with BDD (250 mg/kg) inactivated hepatic microsomal PNPH activity by 50% after 60 min. These results suggest that BDD is extensively and rapidly metabolized in mice, and they provide evidence for the formation of reactive intermediates that could play a role in the toxicity of 1, 3-butadiene.
Assuntos
Álcool Desidrogenase/metabolismo , Butadienos/farmacocinética , Sistema Enzimático do Citocromo P-450/metabolismo , Glicóis/farmacocinética , Álcool Desidrogenase/antagonistas & inibidores , Álcool Desidrogenase/urina , Animais , Antioxidantes/farmacologia , Butadienos/urina , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/urina , Inibidores Enzimáticos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Glicóis/urina , Masculino , Camundongos , Camundongos Endogâmicos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologiaRESUMO
Rats were injected subcutaneously with 2,5-hexanedione (2,5-HD 2.6 m mol/kg) alone (HD group) or with 2,5-HD and methyl ethyl ketone (MEK) (2.6 m mol/kg of each agent, HD&MEK group) or with 2,5-HD 2.6 m mol/kg and 5 times that dose (13.0 m mol/kg) of MEK (HD&5MEK group). The concentration of 2,5-HD in serum and in the sciatic nerve was determined 0.5, 1, 2, 4, 8, and 16 h after administration. Urinary 2,5-HD concentration was determined from the beginning of administration up to 16 h afterward. 1) The concentration of 2,5-HD in the serum, the sciatic nerve, and the urine was increased significantly (p < 0.05) in the co-administered groups; the higher the MEK doses were, the greater was the increase. 2) The clearance of 2,5-HD from both the serum and the sciatic nerve was delayed in the co-administered groups. The highest concentration in serum and the sciatic nerve appeared at 1 and 2 h respectively. After administration, the biological halflife (t1/2) of 2,5-HD from 1 to 8 h in serum was 6.5, 5.8 and 12.0 h for the HD, HD&MEK, and HD&5 MEK groups respectively. From 8 to 16 h, the t1/2 in serum was 1.2, 3.2 and 16.6 h for the HD, HD&MEK, and HD&5MEK groups, respectively. In nerve tissue, the prolongation of clearance in the co-administered groups was greater than that in serum, the t1/2 from 2 to 8 h being 5.2, 9.6 and 19.9 h for the HD, HD&MEK, and HD&5MEK groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Butanonas/administração & dosagem , Glicóis/análise , Nervo Isquiático/química , Animais , Glicóis/sangue , Glicóis/urina , Meia-Vida , Masculino , Ratos , Ratos WistarRESUMO
A method has been developed for the separation and measurement of ethylene glycol and three other glycols (propylene glycol, 1,3-butylene glycol and 2,3-butylene glycol) in biological samples by wide-bore column gas chromatography with a flame ionization detector. The method used 1,3-propylene glycol (1,3-propanediol) as an internal standard. The method was linear at least from 2 to 1000 micrograms/ml, with a detection limit of 1 microgram/ml. Analytical recoveries were 89-98% for the different concentrations. Precision studies showed coefficients of variation of 1.5-7.7% for the different concentrations. The assay was applied to the analysis of biological samples from two patients who had ingested ethylene glycol and/or other glycols in a suicide attempt.
Assuntos
Glicóis/análise , Adulto , Ácidos Borônicos , Cromatografia Gasosa , Glicóis/sangue , Glicóis/urina , Humanos , Masculino , Desnaturação Proteica , Tentativa de SuicídioRESUMO
The urinary excretion profiles of some metabolites of sulfur mustard were determined by gas chromatography/mass spectrometry after cutaneous application of sulfur mustard in rats. Excretion profiles of the individual metabolites thiodiglycol and thiodiglycol sulfoxide, derived from the hydrolysis of sulfur mustard, were determined in different groups of three rats. Concentrations of thiodiglycol detected increased up to 10 fold after treatment of the urine with hydrochloric acid, presumably because of the excretion of acid-labile esters of thiodiglycol. Free thiodiglycol, free plus esterified thiodiglycol, and thiodiglycol sulfoxide excreted over 8 days accounted for less than 0.3%, 1-1.5%, and 3.4-4.3%, respectively, of the applied dose of sulfur mustard. In a further study, a modified analytical method was applied to determine these hydrolysis products and their acid-labile esters as the single analyte thiodiglycol, after treatment with acidic titanium trichloride. The excretion profile of the combined hydrolysis products was compared with the excretion profile of a different group of metabolites of sulfur mustard derived from the glutathione/beta-lyase pathway. These were also reduced to a common analyte, 1,1'-sulfonylbis-[2-(methylthio)ethane], after similar treatment with titanium trichloride. Urinary excretion of hydrolysis products determined in 4 rats over 8 days accounted for 3.7-13.6% of an applied cutaneous dose of sulfur mustard. Urinary excretion of beta-lyase metabolites accounted for 2.5-5.3% of the applied dose in the same group of rats. The excretion of beta-lyase products showed a much sharper decline than was observed for the hydrolysis products of sulfur mustard.
Assuntos
Glicóis/urina , Gás de Mostarda/farmacocinética , Administração Cutânea , Animais , Hidrólise , Liases/fisiologia , Ratos , Absorção CutâneaRESUMO
The pharmacokinetics of [1,3-14C]-2-ethyl-1,3-hexanediol (EHD) were investigated following single percutaneous doses of 150 mg/kg, applied to male and female Fischer 344 rats, or single peroral doses of 1.5 or 150 mg EHD/kg given by gavage to male Fischer 344 rats. EHD-derived radioactivity was slowly absorbed through skin and relatively rapidly excreted through the urine in a first-order manner over 48 hr postdosing. Skin penetration of 14C was sufficiently slow that the terminal rate constant for the plasma concentration data had to be derived from the absorption phase of this curve, based on the terminal rate constant for a comparable intravenous dose plasma curve [Frantz et al.: Drug Metab. Dispos. 19, 881 (1991)]. Plasma data from perorally doses rats exhibited dose-linearity over a 1.5-150 mg/kg range, with plasma 14C concentration vs. time plots for oral doses of EHD resembling the iv time-course data. This resulted from a very rapid absorption phase (5.5 min t1/2), with plasma 14C levels for both dose levels decreasing in a biexponential manner. The major route of excretion after peroral doses was in urine, making this mode of excretion consistent for both routes of administration evaluated in this study and including the doses given in previous iv work. Kinetic analysis confirmed that this route of excretion was first-order. HPLC analysis of urine from both routes demonstrated that EHD was metabolized and excreted as at least two major, water-soluble urinary metabolites; these metabolites were not identified in this investigation. No unmetabolized EHD was detected in urine, indicating that EHD may be completely metabolized in the rat. Overall, EHD was absorbed, distributed, metabolized, and eliminated from the Fischer rat in a first-order manner following either cutaneous or peroral doses. The results of this study indicate that the kinetic patterns observed experimentally will be dose-proportional for doses administered in the range of 1.5-150 mg/kg.
Assuntos
Glicóis/farmacocinética , Repelentes de Insetos/farmacocinética , Absorção , Administração Cutânea , Administração Oral , Animais , Autorradiografia , Radioisótopos de Carbono , Feminino , Glicóis/sangue , Glicóis/urina , Repelentes de Insetos/sangue , Repelentes de Insetos/urina , Masculino , Ratos , Ratos Endogâmicos F344 , Fatores Sexuais , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
The authors investigated three biochemical indices of peripheral catecholamine activity in 36 depressed inpatients treated with the monoamine oxidase (MAO) inhibitor phenelzine. Platelet MAO activity, urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), and leukocyte beta-adrenergic receptor functions were measured before and during the 4th week of phenelzine treatment. There were significant reductions in platelet MAO activity, urinary MHPG excretion, and depressive symptoms in all of the patients. Responders had the same decrease in MHPG as nonresponders. There were no changes in leukocyte beta-receptor function in a small subgroup of the patients.
Assuntos
Plaquetas/enzimologia , Transtorno Depressivo/tratamento farmacológico , Glicóis/urina , Leucócitos/efeitos dos fármacos , Metoxi-Hidroxifenilglicol/urina , Monoaminoxidase/metabolismo , Fenelzina/uso terapêutico , Receptores Adrenérgicos beta/efeitos dos fármacos , Transtorno Depressivo/metabolismo , Transtorno Depressivo/psicologia , Feminino , Humanos , Leucócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Fenelzina/farmacologia , Escalas de Graduação Psiquiátrica , Receptores Adrenérgicos beta/fisiologiaRESUMO
The metabolites of dopamine (homovanillic acid-HVA), noradrenaline (4-hydroxy-3-methoxy-phenylglycol-HMPG), and serotonin (5-hydroxyindoleacetic acid-5-HIAA) were measured in cerebrospinal fluid (CSF) from 38 patients and urine from 36 patients with typical Rett syndrome (RS) and compared with controls of similar age. CSF metabolite concentrations were the same in the patients and controls. Urinary metabolites expressed per mol creatinine were significantly higher in older RS patients. This difference is partly explained by lower urinary creatinine levels in older RS patients, due to their known reduction in muscle mass. Alterations in CSF or urine biogenic amine metabolite concentrations do not appear to represent the primary abnormality in RS, and their measurement cannot be regarded as a reliable means of diagnosis.
Assuntos
Glicóis/líquido cefalorraquidiano , Glicóis/urina , Ácido Homovanílico/líquido cefalorraquidiano , Ácido Homovanílico/urina , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/urina , Metoxi-Hidroxifenilglicol/líquido cefalorraquidiano , Metoxi-Hidroxifenilglicol/urina , Síndrome de Rett/metabolismo , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Creatinina/urina , Dopamina/metabolismo , Feminino , Humanos , Lactente , Norepinefrina/metabolismo , Síndrome de Rett/líquido cefalorraquidiano , Síndrome de Rett/urina , Serotonina/metabolismoRESUMO
Measurement of total (free + conjugated) 3 methoxy-4-hydroxyphenylglycol (MHPG) in urine has long been used to assess the metabolism of central norepinephrine (NE). However, available data indicate that total MHPG is not a sensitive marker because the portion of urinary MHPG which derives from brain NE is less than was previously assumed. Several arguments support the view that central MHPG excretion is best represented by the urinary MHPG sulfate fraction. Accordingly, a new strategy has been introduced in last years, involving the separate determination of sulfate and glucuronide conjugates of MHPG as respective markers of central and peripheral NE metabolism. Various biochemical and pharmacological data obtained in healthy subjects and in patients with mental diseases support this hypothesis.
Assuntos
Encéfalo/metabolismo , Glicóis/urina , Metoxi-Hidroxifenilglicol/urina , Norepinefrina/metabolismo , Adulto , Encéfalo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervos Periféricos/metabolismo , Estresse Psicológico/metabolismoRESUMO
Levels of 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) were not markedly elevated in a group of 35 panic disorder patients when compared to healthy controls (mean = 2,430 micrograms/day vs. 2,130 micrograms/day). There was a weak association between elevated pretreatment levels of MHPG and a positive treatment response to alprazolam or diazepam. Alprazolam and diazepam may differ in their effects on MHPG.
Assuntos
Transtornos de Ansiedade/urina , Glicóis/urina , Metoxi-Hidroxifenilglicol/urina , Pânico/fisiologia , Adolescente , Adulto , Idoso , Alprazolam/farmacologia , Transtornos de Ansiedade/tratamento farmacológico , Diazepam/farmacologia , Método Duplo-Cego , Medo , Humanos , Pessoa de Meia-Idade , Distribuição AleatóriaRESUMO
A simple method for the determination in urine of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and its conjugated derivatives is described. After an extraction procedure similar to that described by Gaertner and Wiatr [J. Clin. Chem. Clin. Biochem., 18 (1980) 579] isocratic high-performance liquid chromatographic separation is performed. MHPG can be detected by either electrochemical or absorbance detection (278 nm). Free MHPG is determined directly, whereas MHPG sulphate and MHPG glucuronide are determined after enzymic hydrolysis. Since total MHPG, which represents the sum of these substances, is determined separately, a comparison of the results allows the effectiveness of the hydrolysis of the MHPG derivatives for each urine sample to be determined. For quantitation, the method of adding standard amounts of MHPG is used.