A simple method for the determination of ethylene-thiourea (ETU) in biological samples.
(1/23)
A direct, simple, and rapid high-performance liquid chromatographic method has been developed for the determination of ethylene-thiourea (ETU) in biological fluids. Samples were chromatographed on a Lichrosorb RP8 (5 pm) column after extraction with dichloromethane. The mobile phase was a mixture of hexane/isopropyl alcohol/ethyl alcohol (93:6:1 v/v) added with 0.6 mL/L butylamine. Detection was done with a UV detector set at 243 nm. This method was validated to standard criteria. Calibration curves for ETU in 100 microL of 0.9% saline, 500 microL plasma, and 10 mL urine were linear (r2 > 0.99) from 0.05 to 30 microg/mL, 0.025 to 30 microg/mL, and 1 to 100 ng/mL, respectively. The lower limit of detection was 20 ng/mL in plasma, 25 ng/mL in 0.9% saline, and 0.5 ng/mL in urine. (+info)
Correlation between blood ethylenethiourea and thyroid gland disorders among banana plantation workers in the Philippines.
(2/23)
Ethylenebisdithiocarbamates (EBDCs) are metabolized into ethylenethiourea (ETU), a possible human carcinogen and an antithyroid compound. In this study our goal was to correlate ETU levels with the incidence of thyroid gland disorders among banana plantation workers exposed to EBDC. We randomly selected 57 directly exposed workers and 31 indirectly exposed workers from four banana plantations and 43 workers from an organic farm; all subjects underwent complete medical examinations and laboratory tests. Results showed a higher mean thyroid-stimulating hormone measurement among exposed workers compared with the control group, although the levels were well within normal range. Nine of the exposed farmers had abnormal thyroid ultrasound findings, consisting mostly of solitary nodules, compared with three among the control group. Analysis of variance showed significantly different blood ETU levels among the directly exposed, indirectly exposed, and control groups (p < 0.001), but ETU levels in urine were not significantly different (p = 0.10). Environmental ETU levels were below the U.S. Environmental Protection Agency remediation levels. Among farmers with solitary thyroid nodules, we found a very good direct correlation between the size of the nodule and blood ETU level. In this study we showed that blood ETU is a more reliable biomarker for EBDC exposure than urinary ETU; therefore, the determination of blood ETU should be part of medical surveillance efforts among workers exposed to EBDC to detect occurrences of thyroid gland disorders. (+info)
Octopaminergic agonists for the cockroach neuronal octopamine receptor.
(3/23)
The compounds 1-(2,6-diethylphenyl)imidazolidine-2-thione and 2-(2,6-diethylphenyl)imidazolidine showed the almost same activity as octopamine in stimulating adenylate cyclase of cockroach thoracic nervous system among 70 octopamine agonists, suggesting that only these compounds are full octopamine agonists and other compounds are partial octopamine agonists. The quantitative structure-activity relationship of a set of 22 octopamine agonists against receptor 2 in cockroach nervous tissue, was analyzed using receptor surface modeling. Three-dimensional energetics descriptors were calculated from receptor surface model/ligand interaction and these three-dimensional descriptors were used in quantitative structure-activity relationship analysis. A receptor surface model was generated using some subset of the most active structures and the results provided useful information in the characterization and differentiation of octopaminergic receptor. (+info)
Haplotype and functional analysis of four flavin-containing monooxygenase isoform 2 (FMO2) polymorphisms in Hispanics.
(4/23)
OBJECTIVES: Previous work defined two flavin-containing monooxygenase 2 (FMO2) alleles. The major allele, FMO2*2 (g.23,238C>T), encodes truncated inactive protein (p.X472) whereas the minor allele, FMO2*1, present in African- and Hispanic-American populations, encodes active protein (p.Q472). Recently, four common (27 to 51% incidence) FMO2 single nucleotide polymorphisms (SNPs) were detected in African-Americans (N=50); they encode the following protein variants: p.71Ddup, p.V113fs, p.S195L and p.N413 K. Our objectives were to: (1) determine the incidence of these SNPs in 29 Hispanic individuals previously genotyped as g.23,238C (p.Q472) and 124 previously genotyped as homozygous g.23,238 T (p.X472); (2) determine FMO2 haplotypes in this population; and (3) assess the functional impact of SNPs in expressed proteins. METHODS: SNPs were detected via allele-specific oligonucleotide amplification coupled with real-time or electrophoretic product detection, or single strand conformation polymorphism. RESULTS: The g.7,700_7,702dupGAC SNP (p.71Ddup) was absent. The remaining SNPs were present but, except for g.13,732C>T (p.S195L), were less common in the current Hispanic study population versus the previously described African-Americans. Only expressed p.N413 K was as active as p.Q472, as determined by methimazole- and ethylenethiourea-dependent oxidation. Haplotype determination demonstrated that the g.10,951delG (p.V113fs), g.13,732C>T (p.S195L) and g.22,060T>G (p.N413 K) variants segregated with g.23,238C>T (p.X472). CONCLUSIONS: SNPs would not alter FMO2 activity in individuals possessing at least one FMO2*1 allele. It is likely that these SNPs will segregate similarly in African-American populations. Therefore, estimates that 26% of African-Americans and 2-7% of Hispanic-Americans have at least one FMO2*1 allele should closely reflect the percentages producing active FMO2 protein. (+info)
Determination of ethylene thiourea in urine by HPLC-DAD.
(5/23)
Ethylene thiourea (ETU) is a metabolite of ethylenebisdithiocarbamates (EBDCs); it is the best indicator of exposure to these fungicides. Therefore, high-performance liquid chromatography with photodiode-array detection (HPLC-DAD) was optimized and validated for the determination of ETU in human urines. Urine samples were extracted by solid-phase extraction using Extrelut and analyzed using HPLC-DAD set at 231 nm. The analyses were carried out using a mobile phase of 0.01 M phosphate buffer (pH 4.5) on a C18 Uptisphere NEC-5-20, 250- x 4.6-mm x 5-microm column. The internal standard used was 4-pyridinecarboxylic acid hydrazide. The method was successfully validated in compliance with requirements set by the International Committee on Harmonization 1996. The lower limit of quantitation was at 1 microg/L, and the linearity was studied from 1 to 100 microg/L. There were 272 urine samples collected from farmers exposed to EBDCs in different regions in France analyzed in this study. (+info)
Preconcentration and determination of mercury(II) at a chemically modified electrode containing 3-(2-thioimidazolyl)propyl silica gel.
(6/23)
A mercury-sensitive chemically modified graphite paste electrode was constructed by incorporating modified silica gel into a conventional graphite paste electrode. The functional group attached to the (3-chloropropyl) silica gel surface was 2-mercaptoimidazole, giving a new product denoted by 3-(2-thioimidazolyl)propyl silica gel, which is able to complex mercury ions. Mercury was chemically adsorbed on the modified graphite paste electrode containing 3-(2-thioimidazolyl)propyl silica (TIPSG GPE) by immersion in a Hg(II) solution, and the resultant surface was characterized by cyclic and differential pulse anodic stripping voltammetry. One cathodic peak at 0.1 V and other anodic peak at 0.34 V were observed on scanning the potential from -0.1 to 0.8 V (0.01 M KNO3; v = 2.0 mV s(-1) vs. Ag/AgCl). The anodic peak at 0.34 V show an excellent sensitivity for Hg(II) ions in the presence of several foreign ions. A calibration graph covering the concentration range from 0.02 to 2 mg L(-1) was obtained. The detection limit was estimated to be 5 microg L(-1). The precision for six determinations of 0.05 and 0.26 mg L(-1) Hg(II) was 3.0 and 2.5% (relative standard deviation), respectively. The method can be used to determine the concentration of mercury(II) in natural waters contaminated by this metal. (+info)
Evaluation of histological and molecular endpoints for enhanced detection of thyroid system disruption in Xenopus laevis tadpoles.
(7/23)
Amphibian metamorphosis represents a promising model for the identification of thyroid system-disrupting chemicals due to the pivotal role played by thyroid hormones for the initiation and regulation of metamorphosis. An important aspect of bioassay development is the identification and evaluation of sensitive and diagnostic endpoints. In this study, several morphological, histological, and molecular endpoints were evaluated for their utility to detect alterations in thyroid system function after exposure of stage 51 Xenopus laevis tadpoles to various concentrations (1.0, 2.5, 10, 25, and 50 mg/l) of the anti-thyroidal compound ethylenethiourea (ETU). Analysis of developmental stages on exposure day 20 and monitoring of time to fore limb emergence (FLE) revealed retardation and complete arrest of tadpole development at 25 mg/l and 50 mg/l ETU, respectively. Development was not affected by 1.0, 2.5, and 10 mg/l ETU. Histological alterations in the thyroid gland were observed in FLE-displaying tadpoles after exposure to 2.5, 10, and 25 mg/l ETU, as well as in developmentally arrested tadpoles exposed to 50 mg/l ETU. Prevalence and severity of histological changes increased in a concentration-dependent manner. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) showed increased mRNA expression of the alpha- and beta-subunits of thyroid-stimulating hormone (TSHalpha, TSHbeta) in pituitary tissue of tadpoles exposed to 25 and 50 mg/l ETU. Results demonstrate the successful detection of anti-thyroidal effects of ETU in Xenopus laevis tadpoles using various endpoints and highlight the particular sensitivity of thyroid gland histology to detect thyroid system disruption in tadpoles. (+info)
Using small molecules to overcome drug resistance induced by a viral oncogene.
(8/23)
We used small molecule screening to discover compounds and mechanisms for overcoming E6 oncogene-mediated drug resistance. Using high-throughput screening in isogenic cell lines, we identified compounds that potentiate doxorubicin's lethality in E6-expressing colon cancer cells. Such compounds included quaternary ammonium salts, protein synthesis inhibitors, 11-deoxyprostaglandins, and two additional classes of compounds-analogs of 1,3-bis(4-morpholinylmethyl)-2-imidazolidinethione (a thiourea) and acylated secondary amines that we named indoxins. Indoxins upregulated topoisomerase IIalpha, the target of doxorubicin, thereby increasing doxorubicin lethality. We developed a photolabeling strategy to identify targets of indoxin and discovered a nuclear actin-related protein complex as a candidate indoxin target. (+info)