Excretion of Hydroxy Derivatives of Polycyclic Aromatic Hydrocarbons of the Masses 178, 202, 228 and 252 in the Urine of Coke and Road Workers

Abstract

Urinary PAH-metabolite excretion by non-exposed volunteers, temporarily living on a PAH-poor and PAH-rich diet, respectively, as well as by occupationally PAH-exposed coke plant workers and road workers has been studied. Significant differences in the amount of the metabolites excreted in the urine were detected; the ratio of various metabolites was also found to be different. The mass excretion per liter of the metabolites from phenanthrene was found to be for the unexposed volunteers about 3.5μg/1, for coke plant workers about 70μg/l and for road workers about 35 μg/l. For the metabolites of chrysene the values were 0.03 μg/1 2.5 μg/l and 0.09μg/l, respectively, and for the total metabolites of benzo(a)pyrene: 0.006μg/l for unexposed persons, 0.37 μg/l for coke plant workers and 0.019 μg/l for road workers.     

Design, synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors

Seven cyclohexane-bearing C-glucoside derivatives (7, 9, 12, 13 and 17-19) were designed and synthesized as SGLT2 inhibitors starting from a potent SGLT2 inhibitor we discovered in earlier work, (1S)-1-deoxy-1-[4-methoxy-3-(trans-n-propylcyclohexyl)methylphenyl]-D-glucose (1). The in vitro and in vivo biological activities were evaluated by hSGLT2/hSGLT1 inhibition and urinary glucose excretion (UGE), respectively. Among the synthesized compounds 12, the 6-deoxy derivative of 1 was the most active and selective SGLT2 inhibitor (IC50 = 1.4 nmol/L against hSGLT2; selectivity = 1576). Compound 12 was a potent SGLT2 inhibitor, which could induce more urinary glucose than 1 and dapagliflozin in UGE.     

Acute toxicity and metabolism of arsenocholine in mice

The acute toxicity of arsenocholine was examined in mice by oral administration and intravenous injection. The LD₅₀ values of arsenocholine were 6.5 g kg^?1 for oral administration and 187 mg kg^?1 for oral administration and 187 mg kg^?1 for intravenous injection. Decreases of respiration and spontaneous motility were observed in the mice dosed orally at 12 g kg^?1. The animals exhibited ataxia and finally showed paralysis of the hind legs within 20 min of administration. When arsenocholine was administered orally to mice at 5 or 50 mg As kg^?1, the greater part of the arsenic administered was recovered in urine within 96 h. The metabolite of arsenocholine in urine was identified as arsenobetaine by high-performance liquid chromatography-inductively coupled plasma emission spectrometry (HPLC ICP) and fast atom bombardment mass spectrometry (FAB MS). These results suggested that the major part of orally administered arsenocholine was absorbed from the gastrointestinal tract in mice and then rapidly excreted in urine with biotransformation.     

Enhancing effects of an organic arsenic compound,dimethylarsinic acid (cacodylic acid), in a multi-organ carcinogenesis bioassay

The modifying effects of dimethylarsinic acid (DMA) on tumor induction in various organs were examined using a multi-organ rat carcinogenesis bioassay. A total of 124 six-week-old male F344/DuCrj rats were divided randomly into seven groups. For establishment of wide-spectrum initiation, animals in Groups 1–5 were treated with five carcinogens, namely N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N-bis(2-hydroxypropyl)nitrosamine (DHPN) in the first four weeks. After a two-week interval, Groups 1–5 were then given 0, 50, 100, 200 and 400 ppm DMA, respectively, in drinking water. Groups 6 and 7 received 100 and 400 ppm DMA without any carcinogen pretreatment. All rats were sacrificed at the end of week 30. In the initiated groups (Groups 1–5), DMA enhanced tumor development in the urinary bladder, kidney, liver and thyroid gland. The main arsenic species in urine samples was DMA itself. In conclusion, the observed enhancement of carcinogenesis in the urinary tract as well as in the liver and thyroid gland may be directly due to this arsenic compound.     

Increase the accessibility and scale of targeted metabolomics: Construction of a human urinary metabolome-wide multiple reaction monitoring library using directly-coupled reversed-phase and hydrophilic interaction chromatography

Multiple reaction monitoring (MRM) is wildly employed to research drug absorption, distribution, metabolism, excretion and pharmacokinetics in pharmaceutical and clinical laboratories. Recently, scientists in these areas have shown great interest in utilization of metabolomics to evaluate drug efficacy and toxicity. MRM-based targeted metabolomics is intrinsically more sensitive and selective than MS based untargeted metabolomics in complex biological samples. MRM also minimizes data complexity for fast and focused analysis of core metabolites. Nevertheless, to mitigate the intrinsic targeted nature of MRM and promote it as a discovery toolbox for metabolomics, larger scale MRM assays providing more comprehensive biological information are highly desirable. Here, we employed data-dependent and data-independent strategies to perform extensive MS/MS mapping of human urinary metabolome with the assistance of a directly-coupled reversed-phase liquid chromatography and hydrophilic interaction chromatography (RPLC-HILIC) for simultaneous profiling of hydrophilic and hydrophobic metabolites. RPLC-HILIC enables to save time, limit sample consumption and facilitate data interpretation by removing data redundancy occurring between separate RPLC and HILIC methods. Major product ions in the raw MS/MS spectra were used to build a human urinary metabolome-wide MRM library which contains 749 refined MRM tags in negative ion mode with 198 of them being unambiguously or tentatively assigned for particular metabolites. The library relieves researchers from the most time-consuming setup of massive MRM transitions and making an important step toward large-scale targeted urinary metabolomics.     

On the Metabolism of Dipterex

The metabolism of Dipterex in mammals, insects, plants, and microorganisms is discussed. Based on studies with P³²- and C¹⁴- labelled Dipterex the degradation of the insecticide and the different metabolic pathways are indicated. Whereas the detoxification of Dipterex in mammals and in cotton plant proceeds mainly via hydrolysis of the phosphonate C–P bond, its degradation in microorganisms invokes only O–CH₃ ester cleavage. In Prodenia larvae, Dipterex is metabolized preferentially (70%) by hydrolysis of O–methyl ester linkages and to a minor extent (30%) by splitting of C–P bond.     

Verschiebung des radioaktiven Gleichgewichtes 90Sr- 90Y im Organismus von Ratten nach oraler Verabfolgung

Bei unseren Stoffwechseluntersuchungen mit ⁹⁰Sr an Ratten und Kaninchen stellten wir wiederholt fest, daß sich die Aktivität einer Kot- oder Harnprobe verändert. Diese Veränderung der meßbaren Zählraten kann nur auf eine Verschiebung des radioaktiven Gleichgewichtes zwischen ⁹⁰Sr und ⁹⁰Y infolge der Stoffwechselvorgänge im Organismus zurückgefuhrt werden. Auf Grund der unterschiedlichen chemischen und physikalischen Eigenschaften von Strontium und Yttrium tritt bei jedem chemischen Eingriff eine Verschiebung des radioaktiven Gleichgewichtes zwischen ⁹⁰Sr und ⁹⁰Y ein. So bleibt beispielsweise bei der Fällung von Sr als Sulfat das ⁹⁰Y in Lösung und kann unter Einsatz von Trägermaterial fast quantitativ abgetrennt werden.     

LC-MS/MS method for the quantification of myo- and chiro-inositol as the urinary biomarkers of insulin resistance in human urine

A simple LC‐MS/MS method has been developed and validated for the quantification of endogenous myo‐ and chiro‐inositol in human urine. myo‐ and chiro‐Inositol were completely resolved from other carbohydrates and there were no interference peaks in human urine. The correlation coefficient (n = 3) was greater than 0.9991 over the range 0.05–25.0 µg/mL with the weighted (1/C²) least square method. Precision (%RSD) and accuracy (%RE) were 0–10.0% and 0–6.0% for the intra‐day assay (n = 5) and 0–14.3% and 0–10.0% for the inter‐day assay (n = 5). myo‐ and chiro‐Inositol have been shown to be stable in human urine stored at room temperature and for three freeze–thaw cycles. Copyright © 2011 John Wiley & Sons, Ltd.     

Rapid High Performance Liquid Chromatographic Determination of Ampicillin in Human Urine

Abstract

A rapid, sensitive and specific HPLC assay for the determination of ampicillin in human urine is developed.

Ampicillin was directly measured in human urine at 225 nm using a reversed phase column (Synchropack RP-P) and a mobile phase composed of (1:9 methanol-sodium acetate solution, 0.01 M, pH 4). The analysis required no longer than 10 min. Linear correlation between the peak height ratio of ampicillin to cefoxitin sodium (internal standard) and ampicillin concentration in urine over the range 10–100 μg ml^?1 was obtained. The developed method proved to be advantageous as it monitors ampicillin level in urine. Moreover, the urinary excretion of ampicillin in human subjects after an oral administration of 500 mg ampicillin capsules was established using the proposed method.     

Inhibition of urinary calculi—a spectroscopic study

Although herbal medicine is widely employed in inhibition of urinary calculi as an alternative and complementary curative method, the lack of detailed scientific studies that could provide insights into this complex process weakens its validity. The present work targets multitechnique spectroscopic investigations by Raman, infrared absorption, X‐ray photoelectron spectroscopy (XPS), and photoluminescence on the effects of the herb Rotula Aquatica Lour (RAL) on the growth of synthetically prepared magnesium‐based calculi. In addition to the standard magnesium phosphate‐based sample, two other samples were prepared with incorporation of 1 and 2wt% RAL herbal extract. Both, Raman and infrared data show a newberyite structure for the crystals without and with inhibitor. The XPS measurements reveal an unexpected presence of Zn in the sample with bfRAL inhibitor, which, as suggested in the literature, may initiate rapid stone formation, and consequently, contribute to the inhibition process. Furthermore, the existence of metallic Zn can explain the reflectance of the incident light observed in the infrared transmission studies of the unground crystals. A significant increase in magnesium with addition of herbal extract is observed in the XPS data. Also, evidence for Mg O binding between the inhibitor and the phosphate units of urinary calculus is found in XPS and Raman results. Similarity between our photoluminescence measurements and those of in vivo chlorophyll a corroborates to provide additional evidence of Mg‐related inhibition. Copyright © 2009 John Wiley & Sons, Ltd.