Colorimetric detection of Cr{sup 3+} using gold nanoparticles functionalized with 4-amino hippuric acid

Energy Technology Data Exchange (ETDEWEB)

Jin, Weiwei; Huang, Pengcheng; Chen, Yueji; Wu, Fangying, E-mail: fywu@ncu.edu.cn; Wan, Yiqun [Nanchang University, College of Chemistry (China)

2015-09-15

A facile and effective technique for monitoring Cr{sup 3+} concentration based on 4-amino hippuric acid (PAH) decorated Au nanoparticles (PAH-AuNPs) is introduced. The modified AuNPs were easily aggregated in the presence of Cr{sup 3+}, resulting in the color change from red to violet or blue, which is in response to the surface plasmon absorption of dispersed or aggregated nanoparticles. Under the optimized conditions, a good linear relationship (correlation coefficient r = 0.998) was obtained between the ratio of the absorbance at 635 nm to that at 520 nm (A{sub 635 nm}/A{sub 520 nm}), and the concentration of Cr{sup 3+} was over the range of 5.0–120 µM with detection limit of 1.17 µM. This method exhibited excellent selectivity for Cr{sup 3+} over other tested heavy metal ions. Furthermore, there was no significant difference for the parameters of calibration equation between the presence and absence of ethylenediamine tetraacetic acid (EDTA), which suggests that the method can be applied in various real samples owing to the strong masking ability of EDTA. The assay was used to detect the concentrations of Cr{sup 3+} in liquid milk, milk power, and lake water samples with recoveries ranging from 93.5 to 114 %, indicating that the method could be used for extensive practical application. Graphical Abstract: A facile and effective technique for monitoring Cr{sup 3+} based on 4-amino hippuric acid decorated Au nanoparticles is introduced. The modified AuNPs were aggregated in the presence of Cr{sup 3+} resulting in the color change from red to violet or blue, which is in response to the surface plasmon absorption of dispersed or aggregated nanoparticles.

The vapour pressures over saturated aqueous solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate

International Nuclear Information System (INIS)

Apelblat, Alexander; Korin, Eli

2008-01-01

Vapour pressures of water over saturated solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate were determined over the (278 to 322) K temperature range. The determined vapour pressures were used to obtain the water activities, the molar enthalpies of vaporization, and the osmotic coefficients of sodium-D-gluconate

The vapour pressures over saturated aqueous solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate

Energy Technology Data Exchange (ETDEWEB)

Apelblat, Alexander [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel)], E-mail: apelblat@bgu.ac.il; Korin, Eli [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel)

2008-05-15

Vapour pressures of water over saturated solutions of DL-2-aminobutyric acid, 4-aminobutyric acid, sodium-D-gluconate, sodium hippurate, and potassium magnesium-L-aspartate were determined over the (278 to 322) K temperature range. The determined vapour pressures were used to obtain the water activities, the molar enthalpies of vaporization, and the osmotic coefficients of sodium-D-gluconate.

Niveles de fenol y ácido hipúrico en trabajadores de talleres de latoneria y pintura, Maracay, Venezuela, 2016 | Levels of phenol and hippuric acid in workers of workshop of sheet and painting, Maracay, Venezuela, 2016

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Franklin Pacheco

2017-11-01

Full Text Available The use of organic solvents such as benzene and toluene, causes in the people with high exposure a series of serious health effects, among which stand out neurotoxicity and cancer. The objective of this study was to determine the levels of phenol and hippuric acid, in the urine, as biological indicators of exposure to benzene and toluene. A descriptive, observational, cross-correlation and field study was carried out in which 20 workers with occupational exposure to benzene and 20 without occupational exposure participated, with prior informed consent. The Theis-Benedict method was used for the determination of phenol, NIOSH 8300 for hippuric acid and Jaffé modified for the determination of creatinine, in urine samples taken at the end of the working day. Phenol/crea, levels in the exposure group ranged from 98.23 to 102.34 mg/g-crea (Mean = 97.89; SD = 3.69 and 8.21 to 33.21 mg/g-creatinine in the group without exposure (Mean = 15.16; SD = 6.23. In addition, a statistically significant difference (p 0.05. Workers did not wear personal protective equipment (PPE and work under poor hygiene conditions, which increases exposure to benzene. The low concentration of urinary hippuric acid implies a low toluene exposure.

Evaluation of hippuric acid content in goat milk as a marker of feeding regimen.

Science.gov (United States)

Carpio, A; Bonilla-Valverde, D; Arce, C; Rodríguez-Estévez, V; Sánchez-Rodríguez, M; Arce, L; Valcárcel, M

2013-09-01

Organic producers, traders, and consumers must address 2 issues related to milk: authentication of the production system and nutritional differentiation. The presence of hippuric acid (HA) in goat milk samples has been proposed as a possible marker to differentiate the feeding regimen of goats. The objective of this work is to check the hypothesis that HA could be a marker for the type of feeding regimen of goats by studying the influence of production system (conventional or organic) and feeding regimen (with or without grazing fodder). With this purpose, commercial cow and goat milk samples (n=27) and raw goat milk samples (n=185; collected from different breeds, localizations, and dates) were analyzed. Samples were grouped according to breed, feeding regimen, production system, and origin to compare HA content by ANOVA and honestly significant difference Tukey test at a confidence level of ≥95%. Hippuric acid content was obtained by analyzing milk samples with capillary electrophoresis. This method was validated by analyzing part of the samples with HPLC as a reference technique. Sixty-nine raw goat milk samples (of the total 158 samples analyzed in this work) were quantified by capillary electrophoresis. In these samples, the lowest average content for HA was 7±3 mg/L. This value corresponds to a group of conventional raw milk samples from goats fed with compound feed. The highest value of this group was 28±10 mg/L, corresponding to goats fed compound feed plus grass. Conversely, for organic raw goat milk samples, the highest concentration was 67±14 mg/L, which corresponds to goats fed grass. By contrast, the lowest value of this organic group was 26±10 mg/L, which belongs to goats fed organic compounds. Notice that the highest HA average content was found in samples from grazing animals corresponding to the organic group. This result suggests that HA is a good marker to determine the type of goats feeding regimen; a high content of HA represents a diet

Hollow Fiber Supported Liquid Membrane Extraction Combined with HPLC-UV for Simultaneous Preconcentration and Determination of Urinary Hippuric Acid and Mandelic Acid

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Abdulrahman Bahrami

2017-02-01

Full Text Available This work describes a new extraction method with hollow-fiber liquid-phase microextraction based on facilitated pH gradient transport for analyzing hippuric acid and mandelic acid in aqueous samples. The factors affecting the metabolites extraction were optimized as follows: the volume of sample solution was 10 mL with pH 2 containing 0.5 mol·L−1 sodium chloride, liquid membrane containing 1-octanol with 20% (w/v tributyl phosphate as the carrier, the time of extraction was 150 min, and stirring rate was 500 rpm. The organic phase immobilized in the pores of a hollow fiber was back-extracted into 24 µL of a solution containing sodium carbonate with pH 11, which was placed inside the lumen of the fiber. Under optimized conditions, the high enrichment factors of 172 and 195 folds, detection limit of 0.007 and 0.009 µg·mL−1 were obtained. The relative standard deviation (RSD (% values for intra- and inter-day precisions were calculated at 2.5%–8.2% and 4.1%–10.7%, respectively. The proposed method was successfully applied to the analysis of these metabolites in real urine samples. The results indicated that hollow-fiber liquid-phase microextraction (HF-LPME based on facilitated pH gradient transport can be used as a sensitive and effective method for the determination of mandelic acid and hippuric acid in urine specimens.

A method for subtraction of the extrarenal 'background' in dynamic 131I-hippurate renoscintigraphy

International Nuclear Information System (INIS)

Mlodkowska, E.; Liniecki, J.; Surma, M.

1979-01-01

Using a Toshiba GC-401 gamma camera with MDS computer Trinary a new method was developed for subtracting the extrarenal (extracanalicular) 'background' from the count rate recorded over the kidneys after intravenous administration of 131 I-hippurate. Mean subtraction factors of the 'blood' activity curve were calculated from a study of 27 patients who were given 51 Cr-HSA for purposes of conventional renography with 'background' subtraction. The values of the mean subtraction factors anti Fsub(R,L) for the right and left kidney, by which a blood count rate should be multiplied amounted to 0.86 +- 0.12 and 0.79 +- 0.13, respectively. A comparison of the coefficients of variation of the pure renal signal when mean vs. individually determined subtraction factors were used, and the verification of the method in unilaterally nephrectomized patients have demonstrated that determination of the factors, anti Fsub(R,L), for each patient individually is not required and sufficient precision can be obtained by using the method and factors reported in this study. (orig.) [de

Estudo retrospectivo dos níveis de ácido hipúrico urinário em exames de toxicologia ocupacional A retrospective study analysis of urinary hippuric acid levels in occupational toxicology exams

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Kelly Cristina Gonzalez

2010-06-01

Full Text Available O ácido hipúrico é o principal metabólito do tolueno, solvente amplamente utilizado em processos industriais e com importantes efeitos tóxicos, fato que justifica a preocupação em monitorar regularmente sujeitos com risco de exposição ocupacional a este solvente. O objetivo deste trabalho foi avaliar os níveis de ácido hipúrico encontrados em trabalhadores submetidos à monitorização biológica. Foi realizado um estudo retrospectivo com dados dos anos de 2002 a 2005, no qual foram analisados os resultados e a situação do empregado na oportunidade do exame (periódico, demissional e admissional. Os resultados indicam uma redução significativa nos níveis de ácido hipúrico em 2005. Exames periódicos obtiveram resultados superiores aos exames admissionais e demissionais, e não foi verificada diferença significativa nas proporções dos sujeitos agrupados de acordo com a situação funcional em cada um dos intervalos estabelecidos segundo o valor de referência e o índice biológico máximo permitido. Os níveis de ácido hipúrico detectados indicam um baixo de risco de exposição ao tolueno na população avaliada, provavelmente em decorrência da preocupação crescente com a implantação de medidas de higiene ocupacional.Hippuric acid is the primary metabolite of toluene, a solvent widely used in industrial processes with considerable toxic effects, a fact which justifies regularly monitoring individuals with occupational exposure to this solvent. This work aims at evaluating urinary hippuric acid levels found in workers subject to biological monitoring. A retrospective study was carried out with data referring from 2002 to 2005, in which exams results and employment status were analyzed (periodic, post-employment, and pre-employment exams. Results indicate a significant reduction in hippuric acid levels for 2005. Periodic exams presented higher results than pre-employment and post-employment exams. No significant

Partial molar volumes and viscosities of aqueous hippuric acid solutions containing LiCl and MnCl2 · 4H2O at 303.15 K

Science.gov (United States)

Deosarkar, S. D.; Tawde, P. D.; Zinjade, A. B.; Shaikh, A. I.

2015-09-01

Density (ρ) and viscosity (η) of aqueous hippuric acid (HA) solutions containing LiCl and MnCl2 · 4H2O have been studied at 303.15 K in order to understand volumetric and viscometric behavior of these systems. Apparent molar volume (φv) of salts were calculated from density data and fitted to Massons relation and partial molar volumes (φ{v/0}) at infinite dilution were determined. Relative viscosity data has been used to determine viscosity A and B coefficients using Jones-Dole relation. Partial molar volume and viscosity coefficients have been discussed in terms of ion-solvent interactions and overall structural fittings in solution.

Improved interpretation of renal-vein-renin-ratio by simultaneous determination of renal 131I-hippuric-acid-clearance-ratio in patients with renovascular hypertension

International Nuclear Information System (INIS)

Helber, A.; Boenner, G.; Hummerich, W.; Wambach, G.; Meurer, K.A.; Dvorak, K.; Lent, V.; Zehle, A.; Kaufmann, W.; Koeln Univ.; Staedtisches Krankenhaus Koeln-Merheim; Staedtisches Krankenhaus Koeln-Merheim; Koeln Univ.

1979-01-01

In patients with unilateral vascular kidney disease and hypertension, ratio of renal-vein-renin was compared with 131 I-Hippuric-acid clearance and change in blood pressure during Saralasininfusion. The ratio of renal-vein-renin was positively correlated with the ratio in renal plasma flow between the kidneys in all patients studied. The ratio of renins therefore is a result of two factors: The difference in renin secretion and the difference in blood flow in the two kidneys. In patients with angiotensin independent hypertension renin-ratios up to 2.0 were found without relevance to elevated blood pressure. When the difference in renal blood flow between both kidneys was small, even a slight difference in renal vein renin indicated hypertension related to increased renin secretion. (orig./AJ) [de

Validation of a multi-analyte HPLC-DAD method for determination of uric acid, creatinine, homovanillic acid, niacinamide, hippuric acid, indole-3-acetic acid and 2-methylhippuric acid in human urine.

Science.gov (United States)

Remane, Daniela; Grunwald, Soeren; Hoeke, Henrike; Mueller, Andrea; Roeder, Stefan; von Bergen, Martin; Wissenbach, Dirk K

2015-08-15

During the last decades exposure sciences and epidemiological studies attracts more attention to unravel the mechanisms for the development of chronic diseases. According to this an existing HPLC-DAD method for determination of creatinine in urine samples was expended for seven analytes and validated. Creatinine, uric acid, homovanillic acid, niacinamide, hippuric acid, indole-3-acetic acid, and 2-methylhippuric acid were separated by gradient elution (formate buffer/methanol) using an Eclipse Plus C18 Rapid Resolution column (4.6mm×100mm). No interfering signals were detected in mobile phase. After injection of blank urine samples signals for the endogenous compounds but no interferences were detected. All analytes were linear in the selected calibration range and a non weighted calibration model was chosen. Bias, intra-day and inter-day precision for all analytes were below 20% for quality control (QC) low and below 10% for QC medium and high. The limits of quantification in mobile phase were in line with reported reference values but had to be adjusted in urine for homovanillic acid (45mg/L), niacinamide 58.5(mg/L), and indole-3-acetic acid (63mg/L). Comparison of creatinine data obtained by the existing method with those of the developed method showing differences from -120mg/L to +110mg/L with a mean of differences of 29.0mg/L for 50 authentic urine samples. Analyzing 50 authentic urine samples, uric acid, creatinine, hippuric acid, and 2-methylhippuric acid were detected in (nearly) all samples. However, homovanillic acid was detected in 40%, niacinamide in 4% and indole-3-acetic acid was never detected within the selected samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Simultaneous LC-MS/MS determination of phenylbutyrate, phenylacetate benzoate and their corresponding metabolites phenylacetylglutamine and hippurate in blood and urine.

Science.gov (United States)

Laryea, Maurice D; Herebian, Diran; Meissner, Thomas; Mayatepek, Ertan

2010-12-01

Inborn errors of urea metabolism result in hyperammonemia. Treatment of urea cycle disorders can effectively lower plasma ammonium levels and results in survival in the majority of patients. Available medications for treating urea cycle disorders include sodium benzoate (BA), sodium phenylacetate (PAA), and sodium phenylbutyrate (PBA) and are given to provide alternate routes for disposition of waste nitrogen excretion. In this study, we develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of benzoic acid, phenylacetic acid, phenylbutyric acid, phenylacetylglutamine, and hippuric acid in plasma and urine from children with inborn errors of urea synthesis. Plasma extracts and diluted urine samples were injected on a reverse-phase column and identified and quantified by selected reaction monitoring (SRM) in negative ion mode. Deuterated analogues served as internal standards. Analysis time was 7 min. Assay precision, accuracy, and linearity and sample stability were determined using enriched samples. Quantification limits of the method were 100 ng/ml (0.3-0.8 μmol/L) for all analytes, and recoveries were >90%. Inter- and intraday relative standard deviations were <10%. Our newly developed LC-MS/MS represents a robust, sensitive, and rapid method that allows simultaneous determination of the five compounds in plasma and urine.

Nucleogenic radioiodination of O-iodo hippuric acid (O-I H A) VIA molten acetic acid analogs (A A A). Vol. 3

Energy Technology Data Exchange (ETDEWEB)

El-Shaboury, G; El-Kolaly, M T; El-Watery, A; El-Mohty, A; Raieh, M [Radioisotope Production and Labelled Compounds Department, Hot Laboratories Center, Atomic Energy Authority, Cairo, (Egypt)

1996-03-01

A recent study for nucleogenic radioiodination of O-iodo hippuric acid (O-I H A) in dry-state (i.e. Molten state) with radioiodine in molten acetic acid analogs (AAA) has been investigated. The result investigated has revealed that the molten ammonium acetate (m.p. 114 degree C) fulfills the desired requirements for achieving high and pure radiochemical yield up to 95% within 5 min. at 120 degree C, when used as a molten medium for the no-carrier added isotope - exchange reaction between inactive O-I H A and Lyophilized ethanolic solution of sodium iodide ({sup 131} I{sup -}). On the other hand, the different critical parameters which affects the isotopic - exchange reaction in molten state previously described are discussed to evaluate the chemical principles of the reaction. Also the product obtained is completely free from impurities currently found in commercial radioiodinated - hippuran usually obtained by molten techniques such as glycyl - O - iodihippuric acid (g-OIHA) as well as O-iodobenzonic acid (O-IBA), which are investigated by TIC silica G-60 using the organic phase of the following solvent consists of benzene: acetic acid: water: n.butanol in the ratio of 5:5:2:1 as developing solvent. 2 figs., 2 tabs.

Urinary trans-trans muconic acid (exposure biomarker to benzene) and hippuric acid (exposure biomarker to toluene) concentrations in Mexican women living in high-risk scenarios of air pollution.

Science.gov (United States)

Pruneda-Alvarez, Lucía G; Ruíz-Vera, Tania; Ochoa-Martínez, Angeles C; Pérez-Maldonado, Iván N

2017-11-02

This study aimed to determine t,t-muconic acid (t,t-MA; exposure biomarker for benzene) and hippuric acid (HA; exposure biomarker for toluene) concentrations in the urine of women living in Mexico. In a cross-sectional study, apparently healthy women (n = 104) were voluntarily recruited from localities with a high risk of air pollution; t,t-MA and HA in urine were quantified using a high-performance liquid chromatography (HPLC) technique. Mean urinary levels of t,t-MA ranged from 680 to 1,310 μg/g creatinine. Mean values of HA ranged from 0.38 to 0.87 g/g creatinine. In conclusion, compared to data recently reported in literature, we found high urinary levels of t,t-MA and HA in assessed women participating in this study. We therefore deem the implementation of a strategy aimed at the reduction of exposure as a necessary measure for the evaluated communities.

Biodistribution and biological characteristics of p-[(bis-carboxymethyl) aminomethyl carboxyamino] hippuric acid (Pahida) labelled with technetium-99m. Establishment of pharmacokinetics parameters through compartmental model

International Nuclear Information System (INIS)

Araujo, E.B. de.

1990-01-01

Biologic distribution of p- [(bis-carboxymethylaminomethyl carboxyamino)] hippuric acid (PAHIDA) labeled with sup(99m)Tc in Wistar rats, showed a selective renal uptake among the other organs and tissues. The compound is predominantly eliminated by urinary tract, with small enterohepatic percent of excretion Chromatographic analysis of urine showed the product and possible metabolites. PAHIDA- sup(99m)Tc blood clearance is relatively rapid and a good percent is transported by plasmatic proteins. The percent binding to the erythrocytes is significant after one hour, this is due probably to hydrolysed technetium. The extrapolation of the plasmatic curve denoted the existence of three exponentials, suggesting a model with three compartments: central or intravascular and two peripherics or extravasculars - rapid and slow exchange (retention). Exponential's half life and the transfer constant (k) among the compartments were determined. The compound retention was reaffirmed by whole body determination. The decomposition of the curve in two exponentials allowed to assess the component's half-life. The compartmental model proposed in agreement with the experimental results, showed the complex retention that may be related the binding with the blood components, the possibility of renal metabolization or a structural impediment in the interaction with the tubular cells receptors. (author)

Systemic exposure to benzoic acid and hippuric acid following topical application of clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel in Japanese patients with acne vulgaris.

Science.gov (United States)

Ino, Hiroko; Takahashi, Naoki; Saenz, Alessandra Alio; Wakamatsu, Akira; Hashimoto, Hirofumi; Nakahara, Norie; Hasegawa, Setsuo

2015-01-01

Clindamycin 1%/benzoyl peroxide 3% fixed-dose combination gel (CLDM/BPO3%) is a topical product for the treatment of acne vulgaris. In this study, plasma and urine concentrations of benzoic acid (BA) and hippuric acid (HA) were analyzed to estimate the pharmacokinetics (PK) of BPO after application of CLDM/BPO3% twice-daily for 7 days in Japanese patients with acne vulgaris. Seven-day repeated application of CLDM/BPO3% appears to be safe in this patient population. Concentrations of plasma and urine BA were below the limit of quantification before and after repeated application in most of the 12 adult male patients. Mean difference in Cmax and AUC0-last for plasma HA indicated increased exposures after repeated application, but with wide 90% confidence intervals. Mean Ae0-12 for urine HA was similar before and after repeated application. Repeated application of CLDM/BPO3% is thus unlikely to result in accumulation of BA and HA. The study suggests negligible systemic exposure to BPO metabolites from CLDM/BPO3% after 7-day repeated application in male patients with acne vulgaris. © 2014, The American College of Clinical Pharmacology.

The exercise renogram. A new approach documents renal involvement in systemic hypertension

International Nuclear Information System (INIS)

Clorius, J.H.; Schmidlin, P.

1983-01-01

Hippurate functional scintiscans were obtained in 51 hypertensive patients and in 15 controls. We investigated the influence that posture and exercise have on hippurate kinetics in patients with hypertension. A posture- or exercise-induced disturbance of renal hippurate transport was sought. All persons were examined in prone and standing positions, as well as during exercise. When prone and upright renograms were compared, 24% of the hypertensives demonstrated bilateral orthostatic renal dysfunction. Exercise caused the hippurate transport disturbance to increase. Fifty-seven percent of all hypertensives developed evidence of marked, bilateral, renal dysfunction during ergometric stress, so that exercise renography was shown to be a more sensitive test of the presence of transient tubular dysfunction in hypertension than the standing renogram. In normotensive controls the hippurate functional scintigram failed to be influenced by posture and exercise. The results suggest presence in hypertension of transient, posture- and exercise-mediated alterations of renal cortical blood flow

Exercise renogram. A new approach documents renal involvement in systemic hypertension

International Nuclear Information System (INIS)

Clorius, J.H.; Schmidlin, P.

1983-01-01

Hippurate functional scintiscans were obtained in 51 hypertensive patients and in 15 controls. The authors investigated the influence that posture and exercise have on hippurate kinetics in patients with hypertension. A posture- or exercise-induced disturbance of renal hippurate transport was sought. All persons were examined in prone and standing positions, as well as during exercise. When prone and upright renograms were compared, 24% of the hypertensives demonstrated bilateral orthostatic renal dysfunction. Exercise caused the hippurate transport disturbance to increase. Fifty-seven percent of all hypertensives developed evidence of marked, bilateral, renal dysfunction during ergometric stress, so that exercise renography was shown to be a more sensitive test of the presence of transient tubular dysfunction in hypertension than the standing renogram. In normotensive controls the hippurate functional scintigram failed to be influenced by posture and exercise. The results suggest presence in hypertension of transient, posture- and exercise-mediated alterations of renal cortical blood flow

Glomerular filtration and tubular secretion of MAG-3 in the rat kidney

International Nuclear Information System (INIS)

Mueller-Suur, R.M.; Mueller-Suur, C.

1989-01-01

Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion

Simple technique for measuring relative renal blood flow

International Nuclear Information System (INIS)

Shames, D.M.; Korobkin, M.

1976-01-01

To determine whether externally monitored early renal uptake of 131 I-hippurate is proportional to renal blood flow, the renal uptake of 131 -hippurate at 1 to 2 min after injection was compared with the renal accumulation of radioactive carbonized microspheres in dogs. A renal artery catheter equipped with a balloon was used to decrease renal blood flow unilaterally. One minute after the intravenous injection of 100 μCi of 131 I-hippurate, about 1 μCi of either 85 Sr- or 95 Nb-labeled carbon microspheres was injected into the left ventricle. Radioactivity was measured over both kidneys. The total radioactivity within each kidney region of interest was corrected for background and integrated over the 1 to 2 min interval after injection. Thirteen measurements of relative renal blood flow were made for seven dogs. The dogs were then killed and both kidneys were excised and counted for the radioactivity of the microspheres. The 1 to 2-min relative renal uptake of 131 I-hippurate correlated well with relative microsphere uptake, suggesting that relative renal blood flow can be simply determined from the external measurements of renal uptake of 131 I-hippurate

Improvement of aqueous solubility and rectal absorption of 6-mercaptopurine by addition of sodium benzoate.

Science.gov (United States)

Takeichi, Y; Kimura, T

1994-10-01

The solubility of 6-mercaptopurine (6-MP) in water increased as the concentration of sodium benzoate or sodium hippurate in the solution increased. The solubility of 6-MP in 20% (w/v) sodium benzoate or sodium hippurate solution was about 6-fold larger than that of 6-MP alone. The stability constant of the soluble complex of 6-MP with sodium benzoate was estimated to be 2-8 M-1 from (1) phase-solubility study and (2) analysis of chemical shifts observed in 1H-NMR. Partition of 6-MP from the saturated solution to n-octanol was also greatly increased by the addition of sodium benzoate or sodium hippurate, the degree being less in the latter. Administration of 6-MP with 20% (w/v) sodium benzoate to rat rectum resulted in enhanced absorption and the area under the plasma concentration-time curve was comparable to that obtained by intravenous administration (bioavailability = 100%), while the bioavailability after intrarectal administration of 6-MP with 20% (w/v) sodium hippurate was only 9%. The reason for the difference was discussed.

Studies of liver-specific metabolic reactions with 15N. 1

International Nuclear Information System (INIS)

Hirschberg, K.; Jung, K.; Faust, H.; Matkowitz, R.

1987-01-01

The 15 N tracer technique was used to investigate liver-specific reactions (urea and hippurate synthesis) for studying the metabolism in the healthy and damaged pig liver. After [ 15 N]ammonium chloride administration the tracer distribution on non-protein compounds of serum and urine was followed. Blood samplings before and after liver passage rendered possible a direct analysis of the [ 15 N]ammonium metabolism. The thioacetamide-induced liver damage was used as model for an acute liver intoxication. The capacity for urea synthesis was not influenced by means of this noxious substance, but the metabolism of amino acids and hippuric acid. The considerably depressed excretion of [ 15 N]hippurate seems to be a suitable indicator of liver disfunction. (author)

Studies of liver-specific metabolic reactions with /sup 15/N. 1. Metabolism of /sup 15/N-ammonium chloride in pigs

Energy Technology Data Exchange (ETDEWEB)

Hirschberg, K; Jung, K; Faust, H; Matkowitz, R

1987-07-01

The /sup 15/N tracer technique was used to investigate liver-specific reactions (urea and hippurate synthesis) for studying the metabolism in the healthy and damaged pig liver. After (/sup 15/N)ammonium chloride administration the tracer distribution on non-protein compounds of serum and urine was followed. Blood samplings before and after liver passage rendered possible a direct analysis of the (/sup 15/N)ammonium metabolism. The thioacetamide-induced liver damage was used as model for an acute liver intoxication. The capacity for urea synthesis was not influenced by means of this noxious substance, but the metabolism of amino acids and hippuric acid. The considerably depressed excretion of (/sup 15/N)hippurate seems to be a suitable indicator of liver disfunction.

Reversed phase partition chromatographic separation of Gd(III) on poly(Crown Ether) column

International Nuclear Information System (INIS)

Mahanwar, K.R.; Sabale, S.R.

2014-01-01

A simple method has been developed for the separation of Gd(III) in hippuric acid medium by using poly(dibenzo-18-crown-6) as stationary phase. The effect of hippuric acid concentration, different eluting agent, foreign ions etc was studied and the optimum conditions were established. Breakthrough capacity of poly(dibenzo-18-crown-6) for Gd(III) was found to be 0.572 ±0.01 mmolg -1 of crown polymer. The separation of Gd(III) from other elements in multicomponent mixtures has been achieved. The method was extended for determination of Gd(III) in real sample. The method is simple, rapid and selective with good reproducibility (approximately ± 2%). Crown ethers are widely used as complexing agent that can selectively capture metal cation in their cavity. This special feature shown by poly (dibenzo-18-crown-6) has been used in our laboratory for selective cation exchanger by column chromatography. No attempts were made for the separation of Gd(III) using hippuric acid media and column chromatography. The present communication describes a simple and sensitive method for the determination of Gd(III) using poly(dibenzo-18-crown-6) as stationary phase in hippuric acid medium. The proposed method affords an attractive feature as compared to the solvent extraction technique i.e. it is free from any organic diluents as an environmental concern

[Evaluation of various biochemical parameters in the urine and blood of painters in the carpentry business].

Science.gov (United States)

Sołtys, M; Jakubowska, W; Lenart, E; Nagadowska, H; Lisiecka, M; Ziemer, I; Koćmierkska-Grodzka, D

1986-01-01

The work has been aimed at investigating the effects of organic solvent-toluene-upon the painters of the Building Joinery Factory. Studies carried out during 1978-1980 showed an increased level of toluene metabolite (hippuric acid) in painters' urine, as compared to the environmental control group. The highest level of hippuric acid in painters' urine was found in the first period (first six months) of their job. This was not related to an increase in toluene vapours at the workplace. In painters' blood some irregular and rather small modifications of enzymatic activity were exhibited.

Reliability of two different methods, whole body measurement and shoulder probe measurement, as judged from determinations of the renal clearance of orthoiodine hippuric acid. Methodenvergleich von Ganzkoerper- und Schultersonden-Messtechnik bei der nuklearmedizinischen Nierenclearance-Bestimmung mit Ortho-Jod-Hippursaeure

Energy Technology Data Exchange (ETDEWEB)

Roth, A

1983-05-06

This retrospective study was based on 1300 patients subjected to a series of radiopharmaceutical renal function studies, during which parallel determinations of the renal clearance rate were carried out using whole body measurements and shoulder probe measurements. It was the aim of this analysis to assess the reliability of shoulder probe measurements as compared to that of whole body measurements as well as their suitability for the diagnosis of postural perfusion disorders associated with nephroptosis and to define the generally acceptable normal ranges of the clearance of ortho-iodine hippuric acid on the basis of age and sex groups. As long as the values measured remained within normal limits, no major differences were discernable between the two methods. In reduced renal function, however, the shoulder probe measurements were biassed in a consistent way and tended to an overestimation of the renal performance that was proportionate to the degree of insufficiency. The intra-assay variations observed for the two methods did not differ from each other at a statistically significant level. The systematic error seen in connection with the shoulder probe measurements can in fact be easily eliminated. This method also offers the advantage of greater simplicity and can be carried out with the patient being in an upright position. Its suitability for the detection of postural perfusion disorders still remains to be proven in further studies. The results of the study are of clinical relevance inasfar as it was possible to determine lower limits of OJH clearance for the individual age and sex groups.

Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride.

Science.gov (United States)

Xie, Feifan; Cheng, Zeneng; Li, Sanwang; Liu, Xingling; Guo, Xin; Yu, Peng; Gu, Zhenkun

2014-06-01

Benfotiamine is a lipid-soluble thiamine precursor which can transform to thiamine in vivo and subsequently be metabolized to thiamine monophosphate (TMP) and thiamine diphosphate (TDP). This study investigated the pharmacokinetic profiles of thiamine and its phosphorylated metabolites after single- and multiple-dose administration of benfotiamine in healthy Chinese volunteers, and assessed the bioavailability of orally benfotiamine administration compared to thiamine hydrochloride. In addition, concentration of hippuric acid in urine which is produced in the transformation process of benfotiamine was determined. The results showed that thiamine and its phosphorylated metabolites exhibited different pharmacokinetic characteristics in plasma, blood and erythrocyte, and one-compartment model provided the best fit for pharmacokinetic profiles of thiamine. The transformation process of benfotiamine to thiamine produced large amount of hippuric acid. No accumulation of hippuric acid was observed after multiple-dose of benfotiamine. Compared to thiamine hydrochloride, the bioavailability of thiamine in plasma and TDP in erythrocyte after oral administration of benfotiamine were 1147.3 ± 490.3% and 195.8 ± 33.8%, respectively. The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride. © 2014, The American College of Clinical Pharmacology.

Dgroup: DG00635 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available N) ... D00855 ... Methenamine hippurate (JAN/USP) ... D00856 ... Methenamine mandelate (USP); Hexamine mandelate (JAN) ... D08199 ... Methenamine sulfosalicylate ... ATC code: J01XX05 Antibiotics ...

Examination of the renal function during the first half of pregnancy

International Nuclear Information System (INIS)

Voigt, R.; Stoll, W.

1980-01-01

The renal function of 25 women in the first half of pregnancy was examined by means of sequence scintigrams of the kidneys and by the results of 131 I-hippurate clearance. Up to the 17th week of pregnancy a continuous increase of the clearance equivalents existed. In comparison to non-pregnant women no important changes were observed on the right and on the left above both the ROI of the renal parenchyma and of the renal pelvis. Problems referring to the clearance of paraaminohippuric acid, which is tubularly excreted like 131 I-hippurate, were discussed. Despite of the good suitability of radionuclide methods for screening of the renal function, they should not be applied in early pregnancy because of radioprotective reasons

Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects.

Science.gov (United States)

Frank, Thomas; Netzel, Gabriele; Kammerer, Dietmar R; Carle, Reinhold; Kler, Adolf; Kriesl, Erwin; Bitsch, Irmgard; Bitsch, Roland; Netzel, Michael

2012-08-15

To evaluate health benefits attributed to Hibiscus sabdariffa L. a randomized, open-label, two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract (HSE) on the systemic antioxidant potential (AOP; assayed by ferric reducing antioxidant power (FRAP)) with a reference treatment (water) in eight healthy volunteers. The biokinetic variables were the areas under the curve (AUC) of plasma FRAP, ascorbic acid and urate that are above the pre-dose concentration, and the amounts excreted into urine within 24 h (Ae(0-24) ) of antioxidants as assayed by FRAP, ascorbic acid, uric acid, malondialdehyde (biomarker for oxidative stress), and hippuric acid (metabolite and potential biomarker for total polyphenol intake). HSE caused significantly higher plasma AUC of FRAP, an increase in Ae(0-24) of FRAP, ascorbic acid and hippuric acid, whereas malondialdehyde excretion was reduced. Furthermore, the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers' urine (0.02% of the administered dose). The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans. Furthermore, the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols, most likely caused by the colonic microbiota. Copyright © 2012 Society of Chemical Industry.

Urinary metabolite levels and symptoms in Filipino workers using organic solvents.

Science.gov (United States)

Cucueco, M T; Espinosa, N C; Villanueva, M B; Castro, F T; Sison, S Y; Ortega, V S; Hisanaga, N

1993-01-01

To compare symptoms with urinary metabolite levels, 900 workers from 7 organic solvent-using industries were studied. Urinary metabolites were determined using a high performance liquid chromatograph. Urinary hippuric acid concentrations exceeding the reference value (2.5 g/g creatinine) were found in 78 (8.7%) workers. However, only 3 (0.3%) and 1 (0.1%) of the participants exceeded the reference value for mandelic (0.8 g/g creatinine) and total methylhippuric acid (1.5 g/g creatinine), respectively. The sum of the values of the ratio of measured urinary metabolite concentration to the corresponding ACGIH's biological exposure indices (BEI) [(HA/BEI of HA + MHA/BEI of MHA + MA/BEI of MA)] exceeded 1.0 in 166 (18.4%) workers. Majority of them were from the footwear manufacturing industry (63/129 or 49.2%). Questionnaire interviews were also administered to determine the prevalence of symptoms while at work (acute symptoms) or within the past 6 months (chronic symptoms). Urinary metabolite levels of individual and mixed solvents were compared with the symptoms of all workers. Analysis using Spearman's rank correlation showed in workers whose urinary hippuric acid exceeded 3.75 g/g creatine (1.5 x BEI), significant correlation between their hippuric acid levels and subjective complaints. Workers whose sum of the values of the ratio of measured urinary metabolite concentration to corresponding BEI exceeded 1.5 were selected and comparing this level with their symptoms, significant correlation was also noted in some complaints.

Biological monitoring of blood toluene in exposed printing shop workers; Biologisches Monitoring von Toluol am Beispiel belasteter Druckereiarbeiter

Energy Technology Data Exchange (ETDEWEB)

Hammer, K.D. [Hamburg Univ. (Germany). Ordinariat fuer Hygiene; Pietsch, S. [Hamburg Univ. (Germany). Ordinariat fuer Hygiene; Pfeiffer, E.H. [Hamburg Univ. (Germany). Ordinariat fuer Hygiene

1993-11-01

42 toluene exposed printing workers were monitored and the results compared with those of a control group of 45 blood donors. Monitoring was done by means of blood toluene and hippuric acid excretion measurements. The mean indoor air concentration of toluene amounted to 230 mg/m{sup 3}. The blood toluene averaged up to 830 {mu}g/l. The median of hippuric acid excretion was in the range of 0,405 mg/mg creatinine for the control group and 1,938 mg/mg creatinine for the exposed group respectively. Hippuric acid showed a positive correlation toward ORSA-tube toluene measurements with good significance (p=0,000). Considerable high individual deviations in toluene metabolism occurred, and were discussed as a result of smoking and drinking behavior. (orig.) [Deutsch] 42 Druckereiarbeiter, die einer Raumluft mit einer mittleren Toluolkonzentration von 230 {mu}g/m{sup 3} exponiert waren, wurden untersucht und die Ergebnisse einer unbelasteten Kontrollgruppe bestehend aus 45 Blutspendern gegenuebergestellt. Als Parameter fuer ein biologisches Monitoring wurde die Blut-Toluolkonzentration und die Exkretion von Hippursaeure verwendet. Die Blut-Toluolkonzentration lag im Mittel bei 830 {mu}g/l. Der Mittelwert der Hippursaeure im Urin der unbelasteten Gruppe lag bei 0,405 mg/mg Kreatinin und der belasteten Gruppe bei 1,938 mg/mg Kreatinin. Die Hippursaeureausscheidung war hoch signifikant mit den Werten der ORSA-Roehrchen fuer die Luft-Toluolkonzentration korreliert (p=0,000). Erhebliche individuelle Abweichungen im Toluol-Metabolismus wurden deutlich und anhand von Rauch- und Trinkgewohnheiten diskutiert. (orig.)

Kidney compartment model

International Nuclear Information System (INIS)

Gullberg, G.T.

1976-09-01

A multiparameter kidney compartment model which quantitates the amount of iodohippurate concentration as a function of time in the blood, tissue, kidneys and bladder is developed from a system of differential equations which represent first order kinetics. The kinetic data are obtained using a gamma camera and an HP5407 computer system which allows one to delineate areas of interest for the blood and tissue, kidneys, and bladder thus separating the data into four data sets. The estimated tubular transit times have a high ratio of the signal to the variance whereas the estimates of the amount of iodohippurate in the blood, tissue and kidneys have a low ratio of the signal to the variance. Application of this model to patient data requires better statistics than available with conventional 131 I-hippurate doses; thus a true test of the efficacy awaits availability of 123 I-hippurate

Estimation of technetium 99m mercaptoacetyltriglycine plasma clearance by use of one single plasma sample

International Nuclear Information System (INIS)

Mueller-Suur, R.; Magnusson, G.; Karolinska Inst., Stockholm; Bois-Svensson, I.; Jansson, B.

1991-01-01

Recent studies have shown that technetium 99m mercaptoacetyltriglycine (MAG-3) is a suitable replacement for iodine 131 or 123 hippurate in gamma-camera renography. Also, the determination of its clearance is of value, since it correlates well with that of hippurate and thus may be an indirect measure of renal plasma flow. In order to simplify the clearance method we developed formulas for the estimation of plasma clearance of MAG-3 based on a single plasma sample and compared them with the multiple sample method based on 7 plasma samples. The correlation to effective renal plasma flow (ERPF) (according to Tauxe's method, using iodine 123 hippurate), which ranged from 75 to 654 ml/min per 1.73 m 2 , was determined in these patients. Using the developed regression equations the error of estimate for the simplified clearance method was acceptably low (18-14 ml/min), when the single plasma sample was taken 44-64 min post-injection. Formulas for different sampling times at 44, 48, 52, 56, 60 and 64 min are given, and we recommend 60 min as optimal, with an error of estimate of 15.5 ml/min. The correlation between the MAG-3 clearances and ERPF was high (r=0.90). Since normal values for MAG-3 clearance are not yet available, transformation to estimated ERPF values by the regression equation (ERPF=1.86xC MAG-3 +4.6) could be of clinical value in order to compare it with the normal values for ERPF given in the literature. (orig.)

Angiotensin converting enzyme inhibition induces alterations to hippuran renography despite unchanged ipsilateral renal blood flow in conscious two-kidney, one clip Goldblatt hypertensive dogs

NARCIS (Netherlands)

Jonker, G J; de Zeeuw, D; Huisman, R M; van der Hem, G K

1988-01-01

We performed experiments in the two-kidney, one clip Goldblatt hypertensive dog to see whether angiotensin converting enzyme (ACE) inhibition could improve the sensitivity of hippurate renography in detecting renal artery stenosis. Ten dogs on a sodium-restricted diet were studied before and after

CHANGES IN RENAL-FUNCTION INDUCED BY ACE-INHIBITION IN THE CONSCIOUS 2-KIDNEY, ONE-CLIP GOLDBLATT HYPERTENSIVE DOG

NARCIS (Netherlands)

JONKER, GJ; VISSCHER, CA; DEZEEUW, D; HUISMAN, RM; PIERS, DA; BEEKHUIS, H; VANDERHEM, GK

In order to study why the diagnostic sensitivity of I-123-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV),

Helicobacter ganmani sp nov., a urease-negative anaerobe isolated from the intestines of laboratory mice

DEFF Research Database (Denmark)

Robertson, B.R.; O'Rourke, J.L.; Vandamme, P.

2001-01-01

, isolates possessed single, bipolar, unsheathed flagella and were urease-negative. They were positive for oxidase and reduced nitrate to nitrite but did not hydrolyse hippurate or indoxyl acetate, grew on charcoal agar and were resistant to cephalothin. 16S rDNA sequences from four strains were determined...

Hepatic metabolism of toluene after gastrointestinal uptake in humans

DEFF Research Database (Denmark)

Bælum, Jesper; Mølhave, Lars; Honoré Hansen, S

1993-01-01

The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene...

A Metabonomic Comparison of Urinary Changes in Zucker and GK Rats

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Liang-Cai Zhao

2010-01-01

Full Text Available To further investigate pathogenesis and pathogenic process of type 2 diabetes mellitus (T2DM, we compared the urinary metabolic profiling of Zucker obese and Goto-kakizaki (GK rats by NMR-based metabonomics. Principal component analysis (PCA on urine samples of both models rats indicates markedly elevated levels of creatine/creatinine, dimethylamine, and acetoacetate, with concomitantly declined levels of citrate, 2-ketoglurarate, lactate, hippurate, and succinate compared with control rats, respectively. Simultaneously, compared with Zucker obese rats, the GK rats show decreased levels of trimethylamine, acetate, and choline, as well as increased levels of creatine/creatinine, acetoacetate, alanine, citrate, 2-ketoglutarate, succinate, lactate, and hippurate. This study demonstrates metabolic similarities between the two stages of T2DM, including reduced tricarboxylic acid (TCA cycle and increased ketone bodies production. In addition, compared with Zucker obese rats, the GK rats have enhanced concentration of energy metabolites, which indicates energy metabolic changes produced in hyperglycemia stage more than in insulin resistance stage.

99mTc-DMSA assessment of unilateral renal function: comparative study of two methods

International Nuclear Information System (INIS)

Llamas, J.M.; Torres, M.; Mallol, J.; Latre, J.M.; Martinez Paredes, M.; Carreras, J.L.

1987-01-01

Results obtained with two different methods of assessing unilateral renal function by measuring the percentage of relative uptake following the administration of a tracing dose of Tc 99m -DMSA are compared in a sample of 40 patients with various conditions. As a reference test, I 131 -hippurate 1'-2' relative uptake, corrected by normalized background and attenuation, was employed. Tc 99m -DMSA relative uptake was determined at 24 hours using the following methods: 1) Percentage of accumulated counts over each renal area in relation to the total, for two minutes, corrected by normalized background and attenuation. 2) Percentage of accumulated counts over each renal area in relation to the total, obtained from the geometrical mean value of accumulated counts in AP and PA projections. A correlation analysis between the two methods, and between these and the reference test, were performed. Good correlations among them (r=0,98 between double-image DMS and Hippurate; p<0,001 in all cases) were found. (author)

EFFECT OF CHRONIC ACE-INHIBITION ON THE DIAGNOSTIC-VALUE OF RENOGRAPHY FOR RENOVASCULAR HYPERTENSION - A PRELIMINARY-REPORT

NARCIS (Netherlands)

VISSCHER, CA; DEZEEUW, D; HUISMAN, RM

1995-01-01

We compared the effects of acute and chronic ACE inhibition (ACEi) on the I-123-hippurate in the stenotic kidney of two 2-kidney, 1-clip hypertensive dogs. In the period after clip implantation poststenotic renograms without ACEi of both dogs were normal. Acute ACEi always resulted in delayed

Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis.

Science.gov (United States)

Kurella Tamura, Manjula; Chertow, Glenn M; Depner, Thomas A; Nissenson, Allen R; Schiller, Brigitte; Mehta, Ravindra L; Liu, Sai; Sirich, Tammy L

2016-12-01

Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis. Copyright © 2016 by the American Society of Nephrology.

Diet effects on urine composition of cattle and N2O emissions.

Science.gov (United States)

Dijkstra, J; Oenema, O; van Groenigen, J W; Spek, J W; van Vuuren, A M; Bannink, A

2013-06-01

Ruminant production contributes to emissions of nitrogen (N) to the environment, principally ammonia (NH3), nitrous oxide (N2O) and di-nitrogen (N2) to air, nitrate (NO3 -) to groundwater and particulate N to surface waters. Variation in dietary N intake will particularly affect excretion of urinary N, which is much more vulnerable to losses than is faecal N. Our objective is to review dietary effects on the level and form of N excreted in cattle urine, as well as its consequences for emissions of N2O. The quantity of N excreted in urine varies widely. Urinary N excretion, in particular that of urea N, is decreased upon reduction of dietary N intake or an increase in the supply of energy to the rumen microorganisms and to the host animal itself. Most of the N in urine (from 50% to well over 90%) is present in the form of urea. Other nitrogenous components include purine derivatives (PD), hippuric acid, creatine and creatinine. Excretion of PD is related to rumen microbial protein synthesis, and that of hippuric acid to dietary concentration of degradable phenolic acids. The N concentration of cattle urine ranges from 3 to 20 g/l. High-dietary mineral levels increase urine volume and lead to reduced urinary N concentration as well as reduced urea concentration in plasma and milk. In lactating dairy cattle, variation in urine volume affects the relationship between milk urea and urinary N excretion, which hampers the use of milk urea as an accurate indicator of urinary N excretion. Following its deposition in pastures or in animal houses, ubiquitous microorganisms in soil and waters transform urinary N components into ammonium (NH4 +), and thereafter into NO3 - and ultimately in N2 accompanied with the release of N2O. Urinary hippuric acid, creatine and creatinine decompose more slowly than urea. Hippuric acid may act as a natural inhibitor of N2O emissions, but inhibition conditions have not been defined properly yet. Environmental and soil conditions at the site of

Toluene metabolism in isolated rat hepatocytes: effects of in vivo pretreatment with acetone and phenobarbital

Energy Technology Data Exchange (ETDEWEB)

Smith-Kielland, A.; Ripel, A. (National Inst. of Forensic Toxicology, Oslo (Norway))

1993-02-01

Hepatocytes isolated from control, acetone- and phenobarbital-pretreated rats were used to study the metabolic conversion of toluene to benzyl alcohol, benzaldehyde, benzoic acid and hippuric acid at low (<100 [mu]M) and high (100-500 [mu]M) toluene concentrations. The baseline formation rates of toluene metabolites (benzyl alcohol, benzoic acid and hippuric acid) were 2.9[+-]1.7 and 10.0[+-]2.3 nmol/mg cell protein/60 min at low and high toluene concentrations, respectively. In vivo pretreatment of rats with acetone and phenobarbital increased the formation of metabolites: at low toluene concentrations 3- and 5-fold, respectively; at high toluene concentrations no significant increase (acetone) and 8-fold increase (phenobarbital). Apparent inhibition by ethanol, 7 and 60 mM, was most prominent at low toluene concentrations: 63% and 69%, respectively, in control cells; 84% and 91% in acetone-pretreated cells, and 32% (not significant) and 51% in phenobarbital-pretreated cells. Ethanol also caused accumulation of benzyl alcohol. The apparent inhibition by isoniazid was similar to that of ethanol at low toluene concentrations. Control and acetone-pretreated cells were apparently resistant towards metyrapone; the decrease was 49% and 64% in phenobarbital-pretreated cells at low and high toluene concentrations, respectively. In these cells, the decrease in presence of combined ethanol and metyrapone was 95% (low toluene concentrations). 4-Methylpyrazole decreased metabolite formation extensively in all groups. Benzaldehyde was only found in the presence of an aldehyde dehydrogenase inhibitor. Increased ratio benzoic/hippuric acid was observed at high toluene concentrations. These results demonstrate that toluene oxidation may be studied by product formation in isolated hepatocytes. However, the influence of various enzymes in the overall metabolism could not be ascertained due to lack of inhibitor specificity. (orig.).

Occupational Exposure of Petroleum Depot Workers to BTEX Compounds

Directory of Open Access Journals (Sweden)

M Rezazadeh Azari

2011-12-01

Full Text Available Background: Benzene, toluene, ethylbenzene and xylene (BTEX are the most important toxic volatile compounds in the air and could be easily absorbed through the respiratory tract. In recent years, the risk of exposure to BTEX compounds, especially benzene as a carcinogen, has been considered in petroleum depot stations. Objective: To assess the occupational exposure of petroleum depot workers in Iran to BTEX compounds. Methods: After completing a questionnaire and assessing occupational exposure to BTEX compounds, 78 (46 exposed and 32 non-exposed depot workers were randomly selected to participate in this study. Air sampling and analysis of BTEX was conducted according to the NIOSH method No. 1501. Analysis of urinary hippuric acid, as an indicator of toluene exposure, was carried out according to NIOSH method No. 8300. Personal monitoring of the high exposure group to BTEX compounds was repeated to verify the results obtained in the first phase of the monitoring. Results: Among the 9 operating groups studied, occupational exposure to benzene and toluene was higher in quality control and gasoline loading operators—the median exposure ranged from 0.16 to 1.63 ppm for benzene and 0.2 to 2.72 ppm for toluene. Median exposure of other group members to BTEX compounds was below the detection limit of analytical method (0.07, 0.06, 0.05, and 0.05 ppm, respectively. The level of toluene exposure measured showed correlation with neither post-shift urinary hippuric acid (Spearman's rho=0.128, p=0.982 nor with the difference between post- and pre-shift urinary hippuric acid (Spearman's rho=0.089, p=0.847 in depot operational workers. Conclusion: Gasoline loading operators are exposed to a relatively high level of benzene.

Hippuran-123 I: labelling and quality control

International Nuclear Information System (INIS)

Barboza, M.F. de; Colturato, M.T.; Herrerias, R.; Muramoto, E.

1992-01-01

The o-iodo hippuric acid labelling with radioiodine is a radiopharmaceutical used with more frequently for evaluation the kidney function. Several reactive kits for labelling with 123 I are prepared. Controls of radiochemical purity and biological distribution are made. The reactive kit of hippuran is kept at 4 C during 2 years. (C.G.C.)

Radionuclide estimation of kidney function in patients with acute renal failure

International Nuclear Information System (INIS)

Ilic, S.; Bogicevic, M.; Stefanovic, V.

1989-01-01

In order to evaluate kidney function radionuclide studies were made in 51 patients with different phases of acute renal failure within the period of six months from the beginning of underlying disease. Low 99m -Tc-DTPA clearance values meaning a marked reduction of glomerular filtration rate in oligoanuric phase, with an improvement but not normalization during diuretic and recovery phase. A decrease of the effective renal plasma flow was also found in 131 I-hippurate studies. In the oligoanuric phase glomerular filtration rate was more severely impaired than renal plasma flow, while in the recovery phase this difference disappeared. In the oligoanuric phase of ARF 99m Tc-DTPA dynamic curves were aplated and those of 131 I-hippurate showed accumulation type, in the diuretic phase hypofunction type with both radionuclides, in the recovery phase a minority of them were completely normalized. It is suggested that radionuclide methods should be used to evaluate and follow up kidney function in patients with different phases of ARF. (orig.) [de

Accumulation and turnover of metabolites of toluene and xylene in nasal mucosa and olfactory bulb in the mouse

International Nuclear Information System (INIS)

Ghantous, H.; Dencker, L.; Danielsson, B.R.G; Gabrielsson, J.; Bergman, K.

1990-01-01

Autoradiography of male mice following inhalation of the radioactively labelled solvents, toluene, xylene, and styrene, revealed an accumulation of non-volatile metabolites in the nasal mucosa and olfactory bulb of the brain. Since no accumulation occurred after benzene inhalation, it was assumed that the activity represented aromatic acids, which are known metabolites of these solvents. This was supported by the finding that also radioactive benzoic acid (main metabolite of toluene) and salicylic acid accumulated in the olfactory bulb. High-performance liquid chromatography revealed that after toluene inhalation (for 1 hr), nasal mucosa and olfactory bulb contained mainly benzoic acid, with a strong accumulation in relation to blood plasma, and considerably less of its blycine conjugate, hippuric acid. After xylene inhalation, on the other hand, methyl hippuric acid dominated over the non-conjugated metabolite, toluic acid. The results indicate a specific, possibly axonal flow-mediated transport of aromatic acids from the nasal mucosa to the olfactory lobe of the brain. The toxicological significance of these results remains to be studied. (author)

Unusual calcium oxalate crystals in ethylene glycol poisoning.

Science.gov (United States)

Godolphin, W; Meagher, E P; Sanders, H D; Frohlich, J

1980-06-01

A patient poisoned with ethylene glycol exhibited the symptoms of (1) hysteria, (2) metabolic acidosis with both a large anion gap and osmolal gap, and (3) crystalluria. However, the shape of the urinary crystals was prismatic and resembled hippurate rather than the expected dipyramidal calcium oxalate dihydrate. X-ray crystallography positively identified them as calcium oxalate monohydrate.

Evaluation of benfurodil vasodilator effects using radioactive ortho-iodine-hippurate

Energy Technology Data Exchange (ETDEWEB)

Kauffman, P; Camargo, E E; Fernandes Neto, J M; Rockmann, R L; Dias Neto, A L; Muraco Neto, B; Leao, L E.P.

1974-07-01

In 15 lower limbs of patients with arterial obstructive disease it is studied the arterial blood flow before and after the arterial injection on benfurodil. The method consisted of the arterial injection Hippuran-/sup 131/I and the analysis of its clearance curves in the leg. The results showed a significant increase of the arterial flow after the use of benfurodil.

Alterations of urinary metabolite profile in model diabetic nephropathy

Energy Technology Data Exchange (ETDEWEB)

Stec, Donald F. [Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Suwan; Stothers, Cody [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Avance, Josh [Berea College, 1916 CPO, Berea, KY 40404 (United States); Denson, Deon [Choctaw Central High School, Philadelphia, MS 39350 (United States); Harris, Raymond [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Voziyan, Paul, E-mail: paul.voziyan@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

2015-01-09

Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

Alterations of urinary metabolite profile in model diabetic nephropathy

International Nuclear Information System (INIS)

Stec, Donald F.; Wang, Suwan; Stothers, Cody; Avance, Josh; Denson, Deon; Harris, Raymond; Voziyan, Paul

2015-01-01

Highlights: • 1 H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS −/− C57BLKS and eNOS −/− C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be useful new tools in

A simple LC-MS/MS method for quantitative analysis of underivatized neurotransmitters in rats urine: assay development, validation and application in the CUMS rat model.

Science.gov (United States)

Zhai, Xue-jia; Chen, Fen; Zhu, Chao-ran; Lu, Yong-ning

2015-11-01

Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25-12,800 ng mL(-1) with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group (n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study.

Science.gov (United States)

Austdal, Marie; Tangerås, Line H; Skråstad, Ragnhild B; Salvesen, Kjell; Austgulen, Rigmor; Iversen, Ann-Charlotte; Bathen, Tone F

2015-09-08

Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia.

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study

Directory of Open Access Journals (Sweden)

Marie Austdal

2015-09-01

Full Text Available Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension. Preeclampsia developed in 26 (4.3% and gestational hypertension in 21 (3.5% women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia.

Application of kernel principal component analysis and computational machine learning to exploration of metabolites strongly associated with diet.

Science.gov (United States)

Shiokawa, Yuka; Date, Yasuhiro; Kikuchi, Jun

2018-02-21

Computer-based technological innovation provides advancements in sophisticated and diverse analytical instruments, enabling massive amounts of data collection with relative ease. This is accompanied by a fast-growing demand for technological progress in data mining methods for analysis of big data derived from chemical and biological systems. From this perspective, use of a general "linear" multivariate analysis alone limits interpretations due to "non-linear" variations in metabolic data from living organisms. Here we describe a kernel principal component analysis (KPCA)-incorporated analytical approach for extracting useful information from metabolic profiling data. To overcome the limitation of important variable (metabolite) determinations, we incorporated a random forest conditional variable importance measure into our KPCA-based analytical approach to demonstrate the relative importance of metabolites. Using a market basket analysis, hippurate, the most important variable detected in the importance measure, was associated with high levels of some vitamins and minerals present in foods eaten the previous day, suggesting a relationship between increased hippurate and intake of a wide variety of vegetables and fruits. Therefore, the KPCA-incorporated analytical approach described herein enabled us to capture input-output responses, and should be useful not only for metabolic profiling but also for profiling in other areas of biological and environmental systems.

Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rats.

OpenAIRE

Wang, R S; Nakajima, T

1992-01-01

Rats were exposed to toluene at a wide range of concentrations from 50 to 4000 ppm for six hours, and the effects of ethanol and phenobarbital (PB) treatments on the pharmacokinetics of toluene metabolism were investigated. Ethanol treatment influenced toluene metabolism mainly at low exposure concentrations. Thus ethanol accelerated the clearance of toluene from blood only when the blood concentration of toluene was not high (less than 360 microM), and ethanol increased hippuric acid (HA) ex...

Impact of environmental volatile organic compounds on otitis media in children: Correlation between exposure and urinary metabolites.

Science.gov (United States)

Kim, So Young; Son, Bu-Soon; Park, Hee-Jin; Oh, Seung Ha; Lee, Jun Ho; Suh, Myung-Hwan; Park, Moo Kyun

2017-02-01

Volatile organic compounds (VOCs) induce inflammatory responses. Tobacco smoke contains numerous VOCs and is a risk factor for otitis media effusion (OME); however, no previous studies have investigated the association between VOCs and OME. We used urinary metabolites and exposure to environmental risk factors to investigate the association between VOC and polycyclic aromatic hydrocarbon exposure and recurrent OME in children. Children with recurrent OME who visited the Otorhinolaryngology Department of Seoul National University Hospital between November 2014 and June 2015 were prospectively enrolled in the study. Recurrent OME was defined as more than two OME episodes over a 6-month period lasting longer than 2 months. The control group consisted of children without OME in the last year. Demographic information, including age, sex, and previous medical history was obtained, and endoscopic examinations of the tympanic membrane were performed. Urinary concentrations of 1-hydroxypyrene, 2-naphthol, hippuric acid, trans, trans-muconic acid (t,t-MA), mandelic acid, phenyl glyoxylic acid, and methyl hippuric acid were analyzed using high-performance liquid chromatography/tandem mass spectroscopy. Environmental factors assessed included house type, age, renovations, the presence of furniture children with OME and 39 controls. Age and sex did not differ between groups. Exposure to passive smoking was significantly more common in the OME group than in the controls (P children. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Iodobell in vivo kits for labelling with 123I or 131I

International Nuclear Information System (INIS)

Koernyei, J.; Horvath, M.; Pszota, A.; Lakatos, M.; Szirtes, L.

1988-01-01

Iodobell in vivo kits provide an easy and fast method for 'on the spot' radioiodination with 123 I (or 131 I). Until now three kits have been developed in the Institute of Isotopes Budapest, the heptadecanoic acid, the hippurate and the MIBG kits. From these, the heptadecanoic acid kit is being tested in humans in Hungary, the other two are under the registration procedure. The Iodobell in vivo kits may contribute to the application of 123 I radioisotope in Hungary. (orig.)

Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance

DEFF Research Database (Denmark)

Christensen, N J; Henriksen, Jens Henrik Sahl

1989-01-01

]IP and 131I-hippurate, whole body clearance from plasma of [3H]NE, as obtained from infusion rate divided by plasma concentration of tracer [1.74 +/- 0.64 (SD) 1/min] was significantly higher than the value obtained by total tracer infusion divided by total plasma area of tracer (1.27 +/- 0.51, P less than 0...... irreversible removal of NE, is smaller than previously estimated due to recycling through the plasma space. Attention has been drawn to limitations of [3H]NE kinetics....

Metabolic effects of dark chocolate consumption on energy, gut microbiota, and stress-related metabolism in free-living subjects.

Science.gov (United States)

Martin, Francois-Pierre J; Rezzi, Serge; Peré-Trepat, Emma; Kamlage, Beate; Collino, Sebastiano; Leibold, Edgar; Kastler, Jürgen; Rein, Dietrich; Fay, Laurent B; Kochhar, Sunil

2009-12-01

Dietary preferences influence basal human metabolism and gut microbiome activity that in turn may have long-term health consequences. The present study reports the metabolic responses of free living subjects to a daily consumption of 40 g of dark chocolate for up to 14 days. A clinical trial was performed on a population of 30 human subjects, who were classified in low and high anxiety traits using validated psychological questionnaires. Biological fluids (urine and blood plasma) were collected during 3 test days at the beginning, midtime and at the end of a 2 week study. NMR and MS-based metabonomics were employed to study global changes in metabolism due to the chocolate consumption. Human subjects with higher anxiety trait showed a distinct metabolic profile indicative of a different energy homeostasis (lactate, citrate, succinate, trans-aconitate, urea, proline), hormonal metabolism (adrenaline, DOPA, 3-methoxy-tyrosine) and gut microbial activity (methylamines, p-cresol sulfate, hippurate). Dark chocolate reduced the urinary excretion of the stress hormone cortisol and catecholamines and partially normalized stress-related differences in energy metabolism (glycine, citrate, trans-aconitate, proline, beta-alanine) and gut microbial activities (hippurate and p-cresol sulfate). The study provides strong evidence that a daily consumption of 40 g of dark chocolate during a period of 2 weeks is sufficient to modify the metabolism of free living and healthy human subjects, as per variation of both host and gut microbial metabolism.

Investigations of renal clearance in nuclear medicine

International Nuclear Information System (INIS)

Oberhausen, E.

1981-01-01

Comparative investigations of PAH- and inulin-clearance and results of investigations with J-131-hippurate and Cr-51-EDTA, which were performed by a partly screened whole body counter including measurements of activity retention of blood samples, are showing good correlation. If the radio-isotope nephrography is worked out together with the decreased retention curve, separate results of the function of both kidneys can be given. Modifications which were tried to analyze a small part of the retention curve instead of the whole body are inaccurate, if they are below 300 ml/min. (orig.) [de

15N liver function tests - concept, validity, clinical use

International Nuclear Information System (INIS)

Faust, H.; Jung, K.; Krumbiegel, P.; Hirschberg, K.; Reinhardt, R.; Junghans, P.

1987-01-01

Several liver function tests using the oral application of a nitrogen compound labelled with 15 N and the subsequent determination of 15 N in a certain fraction of urine by emission spectrometry are described. Because of the key position of the liver in the metabolism of nitrogen compounds the results of these tests allow conclusions concerning disturbances of special liver functions. Instructions for the clinical use of the '[ 15 N]Ammonium Test', '[ 15 N]Hippurate Test' the '[ 15 N]Methacetin Test', and the '[ 15 N]Glycine Test' are given. (author)

Protein-bound solute removal during extended multipass versus standard hemodialysis

DEFF Research Database (Denmark)

Eloot, Sunny; Van Biesen, Wim; Axelsen, Mette

2015-01-01

and middle molecules compared to standard hemodialysis (SHD). Since protein-bound solutes (PBS) exert important pathophysiological effects, we investigated whether MPHD results in improved removal of PBS as well. METHODS: A cross-over study (Clinical Trial NCT01267760) was performed in nine stable HD......), hippuric acid (HA), indole acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (PCS). Dialyser extraction ratio, reduction ratio, and solute removal were calculated for these solutes. RESULTS: Already at 60 min after dialysis start, the extraction ratio in the hemodialyser was a factor 1.4-4 lower...

NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

Science.gov (United States)

Liu, Haiyan; Tayyari, Fariba; Edison, Arthur S; Su, Zhihua; Gu, Liwei

2016-08-01

A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake. Copyright © 2016 Elsevier Inc. All rights reserved.

H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

International Nuclear Information System (INIS)

McClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O'Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B.T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

2010-01-01

Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

Synthesis and Evaluation of Changes Induced by Solvent and Substituent in Electronic Absorption Spectra of New Azo Disperse Dyes Containig Barbiturate Ring

Directory of Open Access Journals (Sweden)

Hooshang Hamidian

2013-01-01

Full Text Available Six azo disperse dyes were prepared by diazotizing 4-amino hippuric acid and coupled with barbituric acid and 2-thiobarbituric acid. Then, the products were reacted with aromatic aldehyde, sodium acetate, and acetic anhydride, and oxazolone derivatives were formed. Characterization of the dyes was carried out by using UV-Vis, FT-IR, 1H NMR and 13C NMR, and mass spectroscopic techniques. The solvatochromic behavior of azo disperse dyes was evaluated in various solvents. The effects of substituents of aromatic aldehyde, barbiturate, and thiobarbiturate ring on the color of dyes were investigated.

Quantitative renal cinescintigraphy with iodine-123 hippuran methodological aspects, kit for labeling of hippuran

International Nuclear Information System (INIS)

Mehdaoui, A.; Pecking, A.; Delorme, G.; Mathonnat, F.; Debaud, B.; Bardy, A.; Coornaert, S.; Merlin, L.; Vinot, J.M.; Desgrez, A.; Gambini, D.; Vernejoul, P. de.

1981-08-01

The development of an extemporaneous kit for the labeling of ortho-iodo-hippuric acid (Hippuran) with iodine 123 allows the performance of a routine quantitative renal cinescintigraphy providing in 20 minutes, and in an absolutely non-traumatic way, a very complete renal morphofunctional study including: a cortical renal scintigraphy, sequential scintigraphies of excretory tract, renal functional curves, tubular, global, and separate clearances for each kidney. This functional quantitative investigation method should take a preferential place in the routine renal balance. The methodology of the technique is explained and compared to classical methods for estimation of tubular, global and separate clearances [fr

Introductory statement: Of receptors and analogs in renin-angiotensin-aldosterone and adrenergic systems

International Nuclear Information System (INIS)

Eliahou, H.E.; Iaina, A.

1980-01-01

This article reports on the role of the octapeptides angiotensin II (A II)-effector and its receptor on hypertensive patients and in animal experiments. By applying the A-II-receptor blockers, vasodilates drugs, β-receptor blockers and by sodium depletion, the behaviour of the blood pressure, the plasmareninactivity, and of the aldosteron were investigated; a comparative investigation between the A II and A III effectors was also carried out. The iodo-hippurate uptake was reduced with an artificially produced renal arterial ischemia. In general, this investigation provided new viewpoints in the understanding of the possible pathogenetic mechanism of essential hypertonism. (APR) [de

Synthesis of selectively 13C-labelled benzoic acid for nuclear magnetic resonance spectroscopic measurement of glycine conjugation activity

International Nuclear Information System (INIS)

Akira, Kazuki; Hasegawa, Hiroshi; Baba, Shigeo

1995-01-01

The synthesis of [4- 13 C]benzoic acid (BA) labelled in a single protonated carbon, for use as a probe to measure glycine conjugation activity by nuclear magnetic resonance (NMR) spectroscopy, has been reported. The labelled compound was prepared by a seven-step synthetic scheme on a relatively small scale using [2- 13 C] acetone as the source of label in overall yield of 16%. The usefulness of [4- 13 C]BA was demonstrated by the NMR spectroscopic monitoring of urinary excretion of [4- 13 C]hippuric acid in the rat administered with the labelled BA. (Author)

Health Risk Assessment and DNA Damage of Volatile Organic Compounds in Car Painting Houses

Directory of Open Access Journals (Sweden)

Patpida Siripongpokin

2014-06-01

Full Text Available Car painters who work near volatile organic compounds (VOCs sources, including paints, solvents and painting processes may be exposed to highly elevated VOCs levels. This study investigates air samples from car painting houses in Thailand to evaluate the health risks following inhalation exposure. Personal air samplings were obtained at nine garages in Phitsanulok, Thailand from June to September 2012. The concentrations of benzene, toluene, ethylbenzene, xylenes, and styrene in the air workplaces were significantly higher than in a control group of office workers (p < 0.05. Toluene, xylene and ethylbenzene were the most abundant species. However, all VOCs in these air samples were lower than TWA limit of Thailand and the OSHA standard. The lifetime cancer and non-cancer risks for the workers exposed to VOCs were also assessed. The average lifetime cancer risk was 41.0 (38.2-47.2 per million, which is in the acceptable risk. The average lifetime non-cancer risk, the HI, was 0.962 (0.643-1.397, which is well below the reference hazard level. Urine samples, collected after 8-h work periods which were analyzed for VOCs metabolites, including t,t muconic acid, hippuric acid, mandelic acid and m-hippuric acid, demonstrate that the average levels of metabolites in car painters and in controls were close. All VOCs metabolites in urine samples were lower than BEI of ACGIH standard. Blood samples, collected after 8-h work periods which were analyzed by single cell gel electrophoresis (comet assay. The DNA damage, assessed by tail moment, demonstrates that the average of tail moment in car painters were significantly higher than in the controls (p < 0.05.

Characterization and Health Risk Assessment of Volatile Organic Compounds in Gas Service Station Workers

Directory of Open Access Journals (Sweden)

Duangduan Yimrungruang

2008-07-01

Full Text Available Gas service station workers who work near volatile organic compounds (VOCs sources, such as gasoline vapor emissions, and motor vehicle exhausts, may be exposed to highly elevated VOCs levels. This study investigates air samples from gas service stations in Thailand to evaluate the health risks following inhalation exposure. Personal air samplings were obtained at nine gas service stations in Chonburi, Thailand from October to December 2007. The concentrations of benzene, toluene, ethylbenzene, xylenes, and hexane in the air from the workplaces were significantly higher than in a control group of office workers (p<0.05. However, all VOCs in these air samples were lower than TWA limit of Thailand and the OSHA standard. Samples of urine, collected after 8-h work periods which were analyzed for VOCs metabolites, including t,t muconic acid, hippuric acid, mandelic acid and m-hippuric acid, demonstrate that the average levels of metabolites in gas service station workers and in controls were close, except for t,t muconic acid of gas service station workers which displayed higher levels than the in the controls. The lifetime cancer and noncancer risks for the workers exposed to VOCs were also assessed. Results show that all nine gas service stations in this study had a elevated lifetime cancer risk ranging from 53 to 630 per million, thus exceeding the normal risk of 1 per million. For noncancer risks, the levels in all gas stations ranged between 0.03 and 0.4, which is well below the reference hazard level of 1.0. Benzene may the most important cause of both cancer and noncancer risk followed by 1,3 butadiene.

synthesis and labelling of some nitrogenous heterocyclic compounds

International Nuclear Information System (INIS)

Mahmoud, A.A.L.

2002-01-01

the imidazole nucleus has wide range of pharmaceutical activities . also , radioiodinated compounds are used in nuclear medicine. this thesis deals with the synthesis of 2-(iodophenyl)-4-oxazoline-5-ons e, which are used as starting materials in the synthesis of the corresponding imidazolinone derivatives. also, it deals with radioiodination f the synthesized compounds to evaluate their application in nuclear medicine. interaction of o- iodo hippuric acid (I) with aromatic aldehydes (i.e., benzaldehyde, p- methoxybenzaldehyde and p- nitrobenzaldehyde) in acetic anhydride and in the presence of fused sodium acetate effected cyclization to afford the corresponding 2-(2-iodophenyl)-4-arylidene- 2-oxazoline-5-ones(l l a-c )

Renal diagnostic nuclear medicine procedures in progressive systemic scleroderma (PSS)

Energy Technology Data Exchange (ETDEWEB)

Ammari, B.; Hotze, A.; Gruenwald, F.; Biersack, H.J.; Blitz, H.; Kuester, W.; Kreysel, H.W.

1989-02-01

The involvement of kidneys in progressive systemic scleroderma (PSS) is one of the most frequent causes of death in this disease. Using clinical criteria and laboratory tests only the frequency of kidney involvement would be clearly underestimated. Invasive diagnostic procedures such as biopsy and angiography can not be applied in those patients. Nuclear medicine techniques (hippurate clearance, DMSA-scan), however, offer non invasive and sensitive methods in the diagnosis of renal involvement in PSS patients. In our study 46 of 76 patients (60%) revealed pathologic findings. The mentioned diagnostic techniques show a high sensitivity and are in agreement with pathological findings described in PSS.

Renal diagnostic nuclear medicine procedures in progressive systemic scleroderma (PSS)

International Nuclear Information System (INIS)

Ammari, B.; Hotze, A.; Gruenwald, F.; Biersack, H.J.; Blitz, H.; Kuester, W.; Kreysel, H.W.

1989-01-01

The involvement of kidneys in progressive systemic scleroderma (PSS) is one of the most frequent causes of death in this disease. Using clinical criteria and laboratory tests only the frequency of kidney involvement would be clearly underestimated. Invasive diagnostic procedures such as biopsy and angiography can not be applied in those patients. Nuclear medicine techniques (hippurate clearance, DMSA-scan), however, offer non invasive and sensitive methods in the diagnosis of renal involvement in PSS patients. In our study 46 of 76 patients (60%) revealed pathologic findings. The mentioned diagnostic techniques show a high sensitivity and are in agreement with pathological findings described in PSS. (orig.) [de

Estimation of 131J-Jodohippurateclearance by a simplified method using a single plasma sample

International Nuclear Information System (INIS)

Botsch, H.; Golde, G.; Kampf, D.

1980-01-01

Theoretical volumes calculated from the reciprocal of the plasma concentration of 131 J-Jodohippurate were compared in 95 patients with clearance values calculated by the 2-compartment-method and in 18 patients with conventional PAH-clearance. For estimating Hippurate-clearance from a single blood sampling the most favorable time is 45 min. after injection (r = 0.96; clearance 400/ml/min.: r = 0.98). Clearance values may be derived from the formula: C = 0.4 + 7.26 V - 0.021 x V 2 (V = injected activity/activity per l plasma taken 45 min. after injection). The simplicity, precision and reproducibility of the above mentioned clearance-method is emphasized. (orig.) [de

Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

Energy Technology Data Exchange (ETDEWEB)

Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

2012-04-13

Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

Analysis of metabolomic patterns in thoroughbreds before and after exercise

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Hyun-Jun Jang

2017-11-01

Full Text Available Objective Evaluation of exercise effects in racehorses is important in horseracing industry and animal health care. In this study, we compared metabolic patterns between before and after exercise to screen metabolic biomarkers for exercise effects in thoroughbreds. Methods The concentration of metabolites in muscle, plasma, and urine was measured by 1H nuclear magnetic resonance (NMR spectroscopy analysis and the relative metabolite levels in the three samples were compared between before and after exercise. Subsequently, multivariate data analysis based on the metabolic profiles was performed using orthogonal partial least square discriminant analysis (OPLS-DA and variable important plots and t-test was used for basic statistical analysis. Results From 1H NMR spectroscopy analysis, 35, 25, and 34 metabolites were detected in the muscle, plasma, and urine. Aspartate, betaine, choline, cysteine, ethanol, and threonine were increased over 2-fold in the muscle; propionate and trimethylamine were increased over 2-fold in the plasma; and alanine, glycerol, inosine, lactate, and pyruvate were increased over 2-fold whereas acetoacetate, arginine, citrulline, creatine, glutamine, glutarate, hippurate, lysine, methionine, phenylacetylglycine, taurine, trigonelline, trimethylamine, and trimethylamine N-oxide were decreased below 0.5-fold in the urine. The OPLS-DA showed clear separation of the metabolic patterns before and after exercise in the muscle, plasma, and urine. Statistical analysis showed that after exercise, acetoacetate, arginine, glutamine, hippurate, phenylacetylglycine trimethylamine, trimethylamine N-oxide, and trigonelline were significantly decreased and alanine, glycerol, inosine, lactate, and pyruvate were significantly increased in the urine (p<0.05. Conclusion In conclusion, we analyzed integrated metabolic patterns in the muscle, plasma, and urine before and after exercise in racehorses. We found changed patterns of metabolites in

Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using 1H NMR analysis.

Science.gov (United States)

Wu, Fang; Zheng, Hua; Yang, Zheng-Teng; Cheng, Bang; Wu, Jin-Xia; Liu, Xu-Wen; Tang, Chao-Ling; Lu, Shi-Yin; Chen, Zhao-Ni; Song, Fang-Ming; Ruan, Jun-Xiang; Zhang, Hong-Ye; Liang, Yong-Hong; Song, Hui; Su, Zhi-Heng

2017-06-05

Chronic liver injury has been shown to cause liver fibrosis due to the sustained pathophysiological wound healing response of the liver, and eventually progresses to cirrhosis. The total alkaloids of Corydalis saxicola Bunting (TACS), a collection of important bioactive ingredients derived from the traditional Chinese folk medicine Corydalis saxicola Bunting (CS), have been reported to have protective effects on the liver. However, the underlying molecular mechanisms need further elucidation. In this study, the urinary metabonomics and the biochemical changes in rats with carbon tetrachloride (CCl 4 )-induced chronic liver injury due to treatment TACS or administration of the positive control drug-bifendate were studied via proton nuclear magnetic resonance ( 1 H NMR) analysis. Partial least squares-discriminate analysis (PLS-DA) suggested that metabolic perturbation caused by CCl 4 damage was recovered with TACS and bifendate treatment. A total of seven metabolites including 2-oxoglutarate, citrate, dimethylamine, taurine, phenylacetylglycine, creatinine and hippurate were considered as potential biomarkers involved in the development of CCl 4 -induced chronic liver injury. According to pathway analysis using identified metabolites and correlation network construction, the tricarboxylic acid (TCA) cycle, gut microbiota metabolism and taurine and hypotaurine metabolism were recognized as the most affected metabolic pathways associated with CCl 4 chronic hepatotoxicity. Notably, the changes in 2-oxoglutarate, citrate, taurine and hippurate during the process of CCl 4 -induced chronic liver injury were significantly restored by TACS treatment, which suggested that TACS synergistically mediated the regulation of multiple metabolic pathways including the TCA cycle, gut microbiota metabolism and taurine and hypotaurine metabolism. This study could bring valuable insight to evaluating the efficacy of TACS intervention therapy, help deepen the understanding of the

Occupational Toluene Exposure Induces Cytochrome P450 2E1 mRNA Expression in Peripheral Lymphocytes

Science.gov (United States)

Mendoza-Cantú, Ania; Castorena-Torres, Fabiola; de León, Mario Bermúdez; Cisneros, Bulmaro; López-Carrillo, Lizbeth; Rojas-García, Aurora E.; Aguilar-Salinas, Alberto; Manno, Maurizio; Albores, Arnulfo

2006-01-01

Print workers are exposed to organic solvents, of which the systemic toxicant toluene is a main component. Toluene induces expression of cytochrome P450 2E1 (CYP2E1), an enzyme involved in its own metabolism and that of other protoxicants, including some procarcinogens. Therefore, we investigated the association between toluene exposure and the CYP2E1 response, as assessed by mRNA content in peripheral lymphocytes or the 6-hydroxychlorzoxazone (6OH-CHZ)/chlorzoxazone (CHZ) quotient (known as CHZ metabolic ratio) in plasma, and the role of genotype (5′-flanking region RsaI/PstI polymorphic sites) in 97 male print workers. The geometric mean (GM) of toluene concentration in the air was 52.80 ppm (10–760 ppm); 54% of the study participants were exposed to toluene concentrations that exceeded the maximum permissible exposure level (MPEL). The GM of urinary hippuric acid at the end of a work shift (0.041 g/g creatinine) was elevated relative to that before the shift (0.027 g/g creatinine; p < 0.05). The GM of the CHZ metabolic ratio was 0.33 (0–9.3), with 40% of the subjects having ratios below the GM. However, the average CYP2E1 mRNA level in peripheral lymphocytes was 1.07 (0.30–3.08), and CYP2E1 mRNA levels within subjects correlated with the toluene exposure ratio (environmental toluene concentration:urinary hippuric acid concentration) (p = 0.014). Genotype did not alter the association between the toluene exposure ratio and mRNA content. In summary, with further validation, CYP2E1 mRNA content in peripheral lymphocytes could be a sensitive and noninvasive biomarker for the continuous monitoring of toluene effects in exposed persons. PMID:16581535

Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

International Nuclear Information System (INIS)

Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Kim, Kyu-Bong; Kim, Seon Hwa; Choi, Ki Hwan; Lee, Hwa Jeong

2012-01-01

Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1 H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg −1 ) or co-administration with cimetidine (100 mg kg −1 ), which protects against GI damage. The 1 H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg −1 ) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

Column chromatographic method for the separation of neodymium from uranium and other elements using poly(dibenzo-18-crown-6)

International Nuclear Information System (INIS)

Lad, Shila N.; Mohite, Baburao S.

2014-01-01

A simple and efficient column chromatographic method has been developed for the separation of U (VI), Nd (III) and other metals using poly (dibenzo-18-crown-6) as stationary phase and hippuric acid as a counter ion. The various eluting agents were found efficient eluents for Nd (III). The capacity of crown polymer for Nd (III) was found to be 0.55±0.01mmol/g. The tolerance limits of various cations and anions for Nd (III) were determined. Nd (III) was quantitatively separated from other metal ions in binary as well as multicomponent mixtures. The good separation yields were obtained and had good reproducibility (±2%). The method was simple, rapid and selective. (author)

High-resolution genomic fingerprinting of Campylobacter jejuni and Campylobacter coli by analysis of amplified fragment length polymorphisms

DEFF Research Database (Denmark)

Kokotovic, Branko; On, Stephen L.W.

1999-01-01

A method for high-resolution genomic fingerprinting of the enteric pathogens Campylobacter jejuni and Campylobacter coli, based on the determination of amplified fragment length polymorphism, is described. The potential of this method for molecular epidemiological studies of these species...... is evaluated with 50 type, reference, and well-characterised field strains. Amplified fragment length polymorphism fingerprints comprised over 60 bands detected in the size range 35-500 bp. Groups of outbreak strains, replicate subcultures, and 'genetically identical' strains from humans, poultry and cattle......, proved indistinguishable by amplified fragment length polymorphism fingerprinting, but were differentiated fi-om unrelated isolates. Previously unknown relationships between three hippurate-negative C. jejuni strains, and two C. coil var, hyoilei strains, were identified. These relationships corresponded...

Comparison of angiography, prone renography, and exercise renography for treatment planning in hypertension

International Nuclear Information System (INIS)

Clorius, J.H.; Strauss, L.G.; Allenberg, J.; Hupp, T.; Schmidlin, P.; Irngartinger, G.

1987-01-01

Fifteen hypertensives with unilateral vascular stenosis had selective renal angiograms, prone-position gamma camera hippurate renograms, and upright exercise renograms. The exercise renograms were used to identify renal vasomotor dysfunction. Each procedure was assessed for its value to predict cure of hypertension. Therapy included one nephrectomy, and angioplasty, and 13 surgical revascularizations. Neither the extent of vascular lumen reduction as assessed with angiography nor the unilateral function impairment documented with a prone-position renogram contained useful prognostic data. Exercise renography correctly predicted the posttherapy blood pressure status in 14 of 15 hypertensives. Exercise renography can identify a newly recognized function response of the vasculature of the kidney, a pathologic response that shows promise in the investigation of hypertension

Imaging of uretero-pelvic junction obstruction with stimulated diuresis

International Nuclear Information System (INIS)

Ebel, K.D.; Bliesener, J.A.; Gharib, M.

1988-01-01

Eighty-nine kidneys of 81 infants and children with uretero-pelvic junction obstruction were investigated using ultrasonography (US), diuretic urography (DUR) and diuretic renography (DREN). Results of the US were false-negative in 14%. This can be avoided by ensuring that the patients get an amount of fluid appropriate to their age before the examination or by performing diuretic ultrasonography with frusemide. False-positive results were found with US in 15%, but obstruction was excluded by using the DUR and/or the DREN. During post-operative follow-up the DUS is useful and after 6 months the clearance with 123-iodine hippurate combined with the DREN should be performed. The administration of the Whitaker-test is unnecessary. (orig.)

123I and131I labelled p-iodophenylpentadecanoic acid (p-IPPA): simplified preparation. Biodistribution in mice, rabbits and patients

International Nuclear Information System (INIS)

Angelberger, P.; Wagner-Loeffler, M.; Hruby, R.; Dudczak, R.; Schmoliner, R.; Kletter, K.; Frischauf, H.

1981-01-01

In an attempt to avoid the second injection of radioiodide as an internal standard for catabolically released iodide, Machulla et al proposed 15-phenyl-penta-decanoic acid (PPA), labelled at the phenyl ring, for myocardial imaging and metabolic studies. PPA is catabolized via β-oxidation to benzoic acid which is known to be rapidly excreted as hippuric acid. After labelling, three sequential HPLC separations were recommended to purify the labelled p-Isomer (p-IPPA). In this process three intermediate evaporation steps have also to be performed. Thus it seems important to look for improved purification procedures which may possibly reduce the preparation time. The present report compares different purification procedures and relates them to the biodistribution of the final product in mice and rabbits. (Auth.)

Identification of urinary biomarkers after consumption of sea buckthorn and strawberry, by untargeted LC-MS metabolomics

DEFF Research Database (Denmark)

Cuparencu, Catalina Sinziana; Andersen, Maj-Britt Schmidt; Gürdeniz, Gözde

2016-01-01

, strawberry and sea buckthorn, in humans. A randomized controlled single-blinded three-way cross-over meal study was conducted in 16 overweight men. The intervention meals consisted of sea buckthorn puree, strawberry puree or an iso-caloric control drink. Urine samples were collected on each test day at t...... in very low concentrations and therefore not identified. Nine and 11 markers were (tentatively) identified for strawberry and sea buckthorn, respectively, the most specific being conjugates of aroma compounds and coloring flavonoids. Metabolites reflecting the step-wise aromatization of quinic to hippuric...... profiling after consumption of sea buckthorn or strawberries. Combinations of these markers are proposed as potentially specific for intake of each of these berries, but need further validation in larger and less-controlled study settings....

Síntese e hidrólise de azalactonas de Erlenmeyer-Plöchl mediadas por radiação micro-ondas em aparelhos doméstico e dedicado: experimentos de química orgânica para a graduação Synthesis and hydrolysis of Erlenmeyer-Plöchl azalactones mediated by microwave radiation in domestic and dedicated ovens: undergraduate organic chemistry experiments

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Silvio Cunha

2013-01-01

Full Text Available This work describes a green chemistry experiment for the synthesis of Erlenmeyer-Plöchl azalactones mediated by microwave irradiation, employing both dedicated and domestic equipment. Hippuric acid was reacted with equimolar amounts of benzaldehyde, p-chloro-benzaldehyde or p-N,N-dimethyl-benzaldehyde in acetic anhydride as the solvent. Acid hydrolysis of obtained 4-benzylidene-2-phenyloxazol-5(4H-one under microwave and convectional heating afforded Z-α-(benzoylaminocinnamic acid at a 51-61.5% yield. The UV-Vis molecular spectra of 4-benzylidene-2-phenyloxazol-5(4H-one and 4-(4'-N,N-dimethylbenzylidene-2-phenyloxazol-5(4H-one were obtained in ethanol, CH2Cl2 and DMSO and bathochromic shift was observed for the latter azalactone.

Detection of the pyrogen in the radiopharmaceuticals using Limulus test and inhibitory factors in the gelation reaction

International Nuclear Information System (INIS)

Murata, Hajime; Iio, Masahiro; Yamada, Hideo; Chiba, Kazuo; Kobayashi, Masayoshi.

1975-01-01

To examine the sensitivities of the Limulus test and the inhibitory factors in radiopharmaceuticals, the following procedures were employed. Twenty commonly used radiopharmaceuticals were examined by Limulus Lysate (Pre-gel). In order to detect the inhibitory factors, several doses of endotoxin (E. coli) were added to the radiopharmaceuticals before the Limulus test was made and the results were compared with control results using saline solution of endotoxin. When the pH of the reaction solution lay out of a suitable range (6.0-7.5), the pH was adjusted by Tris-HCl buffer before the reaction. The sensitivity of the Limulus test control using Pre-gel was positive at a concentration of 10 -3 μg/ml of endotoxin. The Limulus test was sensitive and without inhibitory reactions for sup(99m)TcO 4 -, sup(99m)Tc-albumin, sup(99m)Tc-MAA, sup(99m)Tc-Sn-colloid, 131 I-hippurate, Na 131 I, Na 2 51 CrO 4 , 67 Ga-citrate and 57 Co-bleomycin as they were supplied. 111 In-DTPA, sup(99m)Tc-phytate, sup(99m)Tc-pyrophosphate, sup(99m)Tc-DTPA, 131 I-PVP, 59 FeCl 3 , Na-phosphate ( 32 P), 198 Au-colloid and 75 Se-selenomethionine needed to have their pH adjusted to avoid inhibition. Benzyl alcohol in the radiopharmaceutical showed an inhibitory effect at a concentration greater than 1%. Commonly used 169 Yb-DTPA which was evaluated by this test had a sensitivity of 2.5 x 10 -3 μg/ml due to addition of a small amount of benzyl alcohol. 131 I-BSP showed intense inhibition in gelation reaction. Contaminations of endotoxin were detected in sup(99m)Tc-albumin, sup(99m)Tc-Sn-colloid, 131 I-hippurate, Na 131 I, Na 2 51 CrO 4 , 198 Au-colloid, 57 Co-bleomycin and 75 Se-selenomethionine. (auth.)

Toluene inducing acute respiratory failure in a spray paint sniffer.

Science.gov (United States)

Peralta, Diego P; Chang, Aymara Y

2012-01-01

Toluene, formerly known as toluol, is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent. Like other solvents, toluene is sometimes also used as an inhalant drug for its intoxicating properties. It has potential to cause multiple effects in the body including death. I report a case of a 27-year-old male, chronic spray paint sniffer, who presented with severe generalized muscle weakness and developed acute respiratory failure requiring ventilatory support. Toluene toxicity was confirmed with measurement of hippuric acid of 8.0 g/L (normal <5.0 g/L). Acute respiratory failure is a rare complication of chronic toluene exposure that may be lethal if it is not recognized immediately. To our knowledge, this is the second case of acute respiratory failure due to toluene exposure.

NMR-based metabolomic profiling of overweight adolescents

DEFF Research Database (Denmark)

Zheng, Hong; Yde, Christian C; Arnberg, Karina

2014-01-01

The plasma and urine metabolome of 192 overweight 12-15-year-old adolescents (BMI of 25.4 ± 2.3 kg/m(2)) were examined in order to elucidate gender, pubertal development measured as Tanner stage, physical activity measured as number of steps taken daily, and intra-/interindividual differences...... and the metabolome could be identified. The present study for the first time provides comprehensive information about associations between the metabolome and gender, pubertal development, and physical activity in overweight adolescents, which is an important subject group to approach in the prevention of obesity...... affecting the metabolome detected by proton NMR spectroscopy. Higher urinary excretion of citrate, creatinine, hippurate, and phenylacetylglutamine and higher plasma level of phosphatidylcholine and unsaturated lipid were found for girls compared with boys. The results suggest that gender differences...

Comparison of aspirin renogram and captopril renogram in the diagnosis of renovascular hypertension

International Nuclear Information System (INIS)

Dabiri Oskoie, S.; Argani, H.

2002-01-01

Renal artery stenosis is the most common cause of secondary hypertension. Preliminary data indicate that aspirin renography with hippurate may be more sensitive for detection renal artery stenosis. In this study 20 patients with known or suspected renal artery stenosis underwent aspirin renography (20 mg/kg orally 1 hour before injection of radiotracer) and captopril renography (50 mg orally) with 99 Tc-DTPA. Renal angiography was performed in all patients. Of the 20 patients enrolled, 11 had unilateral renal artery stenosis on angiography. Captopril renography was positive in 10 patients (915 sensitivity and 90% specificity). Aspirin renogram showed 9 patients with renal artery stenosis correctly (81.85 sensitivity and 100% specificity). Our data suggest that aspirin renography with 99 Tc-DTPA has comparable sensitivity with captopril in detection of unilateral renal artery stenosis

Studies on drug metabolism by use of isotopes, 22

International Nuclear Information System (INIS)

Horie, Masanobu; Baba, Shigeo

1978-01-01

The human urinary metabolites of 3-phenylpropyl carbamate (I) were analysed by using an ion cluster technique. After oral administration of an equimolar mixture of non-labeled I and deuterium labeled I, neutral metabolites were extracted with ethyl acetate at pH 7.0, trimethylsilylated and subjected to gas chromatograph-mass spectrometer. In the case of the analysis of acidic metabolites, the urine of human receiving deuterium labeled I alone was used. The obtained acidic metabolites were methylated with diazomethane and subjected to gas chromatograph-mass spectrometer. As neutral metabolites, 3-hydroxy-3-phenylpropyl carbamate 2,3-dihydroxy-3-phenylpropyl carbamate and 3,4'-dihydroxy-3-phenylpropyl carbamate were identified. Unchanged I, however, was not detected. Benzoic and hippuric acids originated from I could be clearly distinguished from the corresponding compounds endogenously produced. (auth.)

Identification of campylobacteria isolated from Danish broilers by phenotypic tests and species-specific PCR assays

DEFF Research Database (Denmark)

Wainø, M.; Bang, Dang Duong; Lund, Marianne

2003-01-01

campylobacterial cultures, 108 Campylobacter jejuni cultures and 351 campylobacterial cultures other than Camp. jejuni were subjected to various species-specific PCR assays. On the basis of the genotypic tests, it was demonstrated that Camp. jejuni and Camp. coli constituted approx. 99% of all cultures, while...... other species identified were Helicobacter pullorum, Camp. lari and Camp. upsaliensis. However, 29% of the 309 Camp. coli cultures identified by phenotypic tests were hippurate-variable or negative Camp. jejuni cultures, whereas some Camp. lari cultures and unspeciated campylobacter cultures belonged...... and Impact of the Study: Future phenotypic test schemes should be designed to allow a more accurate differentiation of Campylobacter and related species. Preferably, the phenotypic tests should be supplemented with a genotypic strategy to disclose the true campylobacterial species diversity in broilers....

Renal sequence and functional series scintigraphy with o131I-hippuric acid in patients with diabetes mellitus

International Nuclear Information System (INIS)

Kempken, K.; Heidenreich, P.; Langhammer, H.; Bottermann, P.; Pabst, H.W.; Technische Univ. Muenchen

1974-01-01

The appearance of disturbances of the renal function in diabetes mellitus is a function of the quality of the therapy and control of the patient, the duration of the disease, and the age of manifestation as well as other factors such as the lipide metabolism and unspecific infections. Such infections often lead to pyelonephritis which may be regarded as a real complication and in particular so in connection with the late diabetic syndrome (Lundbaek), i.e. especially in diabetics of advanced age. Apart from the true diabetic nephropathia, gromerulosclerosis, which is more frequently found in younger patients, arterio-arteriolosclerosis of the kidneys and tubular atrophies due to interstitial deposits of proteins and glycogens should also be mentioned. An assessment of the renal function in all stages of diabetes mellitus and in hypertonicity was carried out with the aid of renal sequential and functional series scintigraphy. No similar investigations have been reported in the relevant literature. (orig./AK) [de

Validation of a simple isotopic technique for the measurement of global and separated renal function

International Nuclear Information System (INIS)

Chachati, A.; Meyers, A.; Rigo, P.; Godon, J.P.

1986-01-01

Schlegel and Gates described an isotopic method for the measurement of global and separated glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on the determination by scintillation camera of the fraction of the injected dose (99mTc-DTPA-[ 131 I]hippuran) present in the kidneys 1-3 min after its administration. This method requires counting of the injected dose and attenuation correction, but no blood or urine sampling. We validated this technique by the simultaneous infusion of inulin and para-amino hippuric acid (PAH) in patients with various levels of renal function (anuric to normal). To better define individual renal function we studied 9 kidneys in patients either nephrectomized or with a nephrostomy enabling separated function measurement. A good correlation between inulin, PAH clearance, and isotopic GFR-ERPF measurement for both global and separate renal function was observed

Reversible diminished renal sup(99m)Tc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis

Energy Technology Data Exchange (ETDEWEB)

Kremer Hovinga, T K; Beukhof, J R; Donker, A J.M.; Luyk, W H.J. van; Piers, D A

1984-03-01

A patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. sup(99m)Tc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of /sup 131/I hippurate was preserved. Uptake of sup(99m)Tc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained. This, caution must be taken when interpreting results of sup(99m)Tc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of /sup 99/Tc-DMSA.

Reversible diminished renal sup(99m)Tc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis

International Nuclear Information System (INIS)

Kremer Hovinga, T.K.; Beukhof, J.R.; Donker, A.J.M.; Luyk, W.H.J. van; Piers, D.A.

1984-01-01

A patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. sup(99m)Tc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of 131 I hippurate was preserved. Uptake of sup(99m)Tc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained. This, caution must be taken when interpreting results of sup(99m)Tc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of 99 Tc-DMSA. (orig.)

Cardiac metabolism of 15 (p-I-123 phenyl-) pentadecanoic acid after intracoronary tracer application

Energy Technology Data Exchange (ETDEWEB)

Reske, S.N.; Reichmann, K.; Knopp, R.; Winkler, C.; Koischwitz, D.; Machulla, H.J.; Simon, H.

1984-05-01

Myocardial turnover of ..omega..-(p/sup 123/I-Phenyl-) pentadecanoic acid and release of its metabolites into the coronary sinus and peripheral blood has been studied in patients with coronary artery and valvular heart disease. After intracoronary tracer injection myocardial extraction fractions of 45-53% in control subjects were observed. In patients with coronary artery disease (CAD) normal to reduced values (34-61%) were established. Hydrophilic catabolites of I-PPA, probably p/sup 123/I-benzoic and -hippuric acid as well as small amounts of the non-metabolized tracer were found in coronary sinus and peripheral blood. Myocardial tracer uptake and clearance patterns were clearly different in normal myocardium when compared to that obtained in patients with CAD. Thus, evaluation of myocardial I-PPA metabolism might provide a new diagnostic tool for assessment of integrity of the heart's muscular metabolic function.

Bacteriological, histological and functional examination of rat kidneys during 5-days gentamycin therapy of experimental E. coli pyelonephritis as compared to 9-days therapy

International Nuclear Information System (INIS)

Hagemann, I.; Briedigkeit, H.; Strangfeld, D.; Ditscherlein, G.; Schuerer, M.; Pietsch, R.; Kruse, L.; Camu, A.; Blank, W.

1985-01-01

Short-term antibiotic treatment is recommended in infections of the lower urinary tract but its effectiveness is questioned in upper urinary tract infections. 5 and 9-days treatment of experimental E. coli 022 pyelonephritis after unilateral nephrectomy in 127 male Wistar rats were compared. 9 mg gentamycin per kg b.w. twice daily were applied. 131 I-hippurate excretion was not decreased during the 5 day treatment but was temporarily diminished during 9-days treatment. Histologically the severe acute pyelonephritis was decreased after 9-days treatment but not after 5 days of treatment. Bacteriologically almost all the kidneys were sterile after 9-days treatment but the majority of the kidneys showed the injected strain of E. coli after 5-days treatment. The results indicated that the shortened treatment was much less effective in acute experimental pyelonephritis. (author)

A simple and accurate grading system for orthoiodohippurate renal scans in the assessment of post-transplant renal function

International Nuclear Information System (INIS)

Zaki, S.K.; Bretan, P.N.; Go, R.T.; Rehm, P.K.; Streem, S.B.; Novick, A.C.

1990-01-01

Orthoiodohippurate renal scanning has proved to be a reliable, noninvasive method for the evaluation and followup of renal allograft function. However, a standardized system for grading renal function with this test is not available. We propose a simple grading system to distinguish the different functional phases of hippurate scanning in renal transplant recipients. This grading system was studied in 138 patients who were evaluated 1 week after renal transplantation. There was a significant correlation between the isotope renographic functional grade and clinical correlates of allograft function such as the serum creatinine level (p = 0.0001), blood urea nitrogen level (p = 0.0001), urine output (p = 0.005) and need for hemodialysis (p = 0.007). We recommend this grading system as a simple and accurate method to interpret orthoiodohippurate renal scans in the evaluation and followup of renal allograft recipients

Detection of the pyrogen in the radiopharmaceuticals using Limulus test and inhibitory factors in the gelation reaction

Energy Technology Data Exchange (ETDEWEB)

Murata, H; Iio, M; Yamada, H; Chiba, K [Tokyo Metropolitan Geriatric Medical Center (Japan); Kobayashi, M

1975-08-01

To examine the sensitivities of the Limulus test and the inhibitory factors in radiopharmaceuticals, the following procedures were employed. Twenty commonly used radiopharmaceuticals were examined by Limulus Lysate (Pre-gel). In order to detect the inhibitory factors, several doses of endotoxin (E. coli) were added to the radiopharmaceuticals before the Limulus test was made and the results were compared with control results using saline solution of endotoxin. When the pH of the reaction solution lay out of a suitable range (6.0-7.5), the pH was adjusted by Tris-HCl buffer before the reaction. The sensitivity of the Limulus test control using Pre-gel was positive at a concentration of 10/sup -3/ ..mu..g/ml of endotoxin. The Limulus test was sensitive and without inhibitory reactions for sup(99m)TcO/sub 4/-, sup(99m)Tc-albumin, sup(99m)Tc-MAA, sup(99m)Tc-Sn-colloid, /sup 131/I-hippurate, Na/sup 131/I, Na/sub 2//sup 51/CrO/sub 4/, /sup 67/Ga-citrate and /sup 57/Co-bleomycin as they were supplied. /sup 111/In-DTPA, sup(99m)Tc-phytate, sup(99m)Tc-pyrophosphate, sup(99m)Tc-DTPA, /sup 131/I-PVP, /sup 59/FeCl/sub 3/, Na-phosphate (/sup 32/P), /sup 198/Au-colloid and /sup 75/Se-selenomethionine needed to have their pH adjusted to avoid inhibition. Benzyl alcohol in the radiopharmaceutical showed an inhibitory effect at a concentration greater than 1%. Commonly used /sup 169/Yb-DTPA which was evaluated by this test had a sensitivity of 2.5 x 10/sup -3/ ..mu..g/ml due to addition of a small amount of benzyl alcohol. /sup 131/I-BSP showed intense inhibition in gelation reaction. Contaminations of endotoxin were detected in sup(99m)Tc-albumin, sup(99m)Tc-Sn-colloid, /sup 131/I-hippurate, Na/sup 131/I, Na/sub 2//sup 51/CrO/sub 4/, /sup 198/Au-colloid, /sup 57/Co-bleomycin and /sup 75/Se-selenomethionine.

Cardiovascular, endocrine and renal effects of urodilatin in normal humans

DEFF Research Database (Denmark)

Bestle, M.H.; Olsen, N.V.; Christensen, P.

1999-01-01

remained below 0.1%. The results indicate that even moderately natriuretic doses of urodilatin exert protracted effects on systemic hemodynamic, endocrine, and renal functions, including decreases in cardiac output and renal blood flow, without changes in arterial pressure or glomerular filtration rate......Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7......-22%) and urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng. kg-1. min-1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood...

Neuronal nitric oxide synthase supports Renin release during sodium restriction through inhibition of phosphodiesterase 3

DEFF Research Database (Denmark)

Sällström, Johan; Jensen, Boye L; Skøtt, Ole

2010-01-01

NOS supports renin release by cyclic guanosine monophosphate (cGMP)-mediated inhibition of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase 3 (PDE3) in juxtaglomerular (JG) cells. METHODS: The experiments were performed in conscious nNOS⁻(/)⁻ and wild types after 10 days on a low-sodium diet...... by measurements of inulin- and para-amino hippuric acid (PAH) clearances, respectively. RESULTS: The basal PRC was reduced in nNOS⁻(/)⁻ compared to the wild types. Administration of milrinone caused a more pronounced PRC increase in nNOS⁻(/)⁻, resulting in normalized renin levels, whereas PDE5 inhibition did...... not affect PRC in any genotype. The blood pressure was similar in both genotypes, and milrinone did not affect blood pressure compared to vehicle. GFR and RPF were similar at baseline and were reduced by milrinone. CONCLUSIONS: The present study provides in vivo evidence supporting the view that NO...

Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines

DEFF Research Database (Denmark)

Stuhr-Hansen, Nicolai; Bork, Nicolai; Strømgaard, Kristian

2014-01-01

The influence of arylthiols on cysteine-free ligation, i.e. the reaction between an alkyl thioester and a primary amine forming an amide bond, was studied in a polar aprotic solvent. We reacted the ethylthioester of hippuric acid with cyclohexylamine in the absence or presence of various quantities...... of thiophenol (PhSH) in a slurry of disodium hydrogen phosphate in dry DMF. Quantitative conversions into the resulting amide were observed within a few hours in the presence of equimolar amounts of thiophenol. Ab initio calculations showed that the reaction mechanism in DMF is similar to the well-known aqueous...... reaction mechanism. The energy barrier of the catalyzed amidation reaction is approximately 40 kJ mol(-1) lower than the non-catalyzed amidation reaction. At least partially this can be explained by a hydrogen bond from the amine to the π-electrons of the thiophenol, stabilizing the transition state...

Current utilization of research reactor on radioisotopes production in China

International Nuclear Information System (INIS)

Liu Yishu

2000-01-01

The main technical parameters of the four research reactors and their current utilization status in radioisotope manufacture and labeling compounds preparation are described. The radioisotopes, such as Co-60 sealed source, Ir-192 sealed source, γ-knife source, I-131, I-125, Sm-153, P-32 series products, In-113m generator, Tc-99m gel generator, Re-188 gel generator, C-14, Ba-131, Sr-89, 90 Y, etc., and their labeling compounds prepared from the reactor produced radionuclides, such as I-131-MIBG, I-131-Hippure, I-131-capsul, Sm-153-EDTMP, Re-186-HEDP, Re-186-HA, C-14-urea, and radioimmunoassay kits etc. are presented as well. Future development plan of radioisotopes and labeling compounds in China is also given. Simultaneously, the possibility and methods of bilateral or multilateral co-operation in utilization of research reactor, personnel and technology exchange of radioisotope production and labeling compounds is also discussed. (author)

An isotope dilution gas chromatography/mass spectrometry method for trace analysis of xylene and its metabolites in tissues following threshold limit value exposures

Energy Technology Data Exchange (ETDEWEB)

Pyon, K.H.; Kracko, D.A.; Strunk, M.R. [and others

1995-12-01

The existence of a nose-brain barrier that functions to protect the central nervous system (CNS) from inhaled toxicants has been postulated. Just as a blood-brain barrier protects the CNS from systemic toxicants, the nose-brain barrier may have similar characteristic functions. One component of interest is nasal xenobiotic metabolism and its effect on the transport of pollutants into the CNS at environmentally plausible levels of exposure. Previous results have shown that inhaled xylene are dimethyl phenol (DMP) and methyl benzyl alcohol (MBA), and the nonvolatile metabolites are toluic acid (TA) and methyl hippuric acid (MHA). The nonvolatile metabolites of xylene, along with a small quantity of volatiles, representing either parent xylene or volatile metabolites, are transported via the olfactory epithelium to the glomeruli within the olfactory bulbs of the brain. Further work will be done to establish the linearity for each analyte at the actual highest detection limit of the GC/MS.

Radioisotope examination of the renal function in gravidic pyelonephritis

Energy Technology Data Exchange (ETDEWEB)

Voigt, R; Stoll, W; Arndt, J [Friedrich-Schiller-Universitaet, Jena (German Democratic Republic). Radiologische Klinik und Poliklinik

1980-08-01

By means of the results of combined renal sequence scintigraphy and /sup 131/I-hippurate clearance in 18 pregnant women with gravidic pyelonephritis as well as in 22 voluntary healthy pregnant women of the corresponding duration of pregnancy and in 13 non-pregnant women without hormonal anticonception as control groups the detection of the renal function with the clinical picture of gravidic pyelonephritis is discussed. The clearance equivalents are represented globally as well as subdivided to the single kidney. Besides typical activity-time curves of the control groups are demonstrated. It was shown that at the time of the most frequent occurrence of gravidic pyelonephritis in the 7th-8th month of pregnancy the clearance equivalents are decreased compared to those of uncomplicated pregnancy. The changes in the course of activity-time curves manifest themselves in a decreased initial phase as well as in an increased excretory phase. Conclusions are drawn for the clinical preliminary diagnosis of risky pregnancies from the results discussed regarding further references.

An isotope dilution gas chromatography/mass spectrometry method for trace analysis of xylene and its metabolites in tissues following threshold limit value exposures

International Nuclear Information System (INIS)

Pyon, K.H.; Kracko, D.A.; Strunk, M.R.

1995-01-01

The existence of a nose-brain barrier that functions to protect the central nervous system (CNS) from inhaled toxicants has been postulated. Just as a blood-brain barrier protects the CNS from systemic toxicants, the nose-brain barrier may have similar characteristic functions. One component of interest is nasal xenobiotic metabolism and its effect on the transport of pollutants into the CNS at environmentally plausible levels of exposure. Previous results have shown that inhaled xylene are dimethyl phenol (DMP) and methyl benzyl alcohol (MBA), and the nonvolatile metabolites are toluic acid (TA) and methyl hippuric acid (MHA). The nonvolatile metabolites of xylene, along with a small quantity of volatiles, representing either parent xylene or volatile metabolites, are transported via the olfactory epithelium to the glomeruli within the olfactory bulbs of the brain. Further work will be done to establish the linearity for each analyte at the actual highest detection limit of the GC/MS

Current utilization of research reactor on radioisotopes production in China

Energy Technology Data Exchange (ETDEWEB)

Liu Yishu [Nuclear Power Institute of China, Chengdu (China)

2000-10-01

The main technical parameters of the four research reactors and their current utilization status in radioisotope manufacture and labeling compounds preparation are described. The radioisotopes, such as Co-60 sealed source, Ir-192 sealed source, {gamma}-knife source, I-131, I-125, Sm-153, P-32 series products, In-113m generator, Tc-99m gel generator, Re-188 gel generator, C-14, Ba-131, Sr-89, {sup 90}Y, etc., and their labeling compounds prepared from the reactor produced radionuclides, such as I-131-MIBG, I-131-Hippure, I-131-capsul, Sm-153-EDTMP, Re-186-HEDP, Re-186-HA, C-14-urea, and radioimmunoassay kits etc. are presented as well. Future development plan of radioisotopes and labeling compounds in China is also given. Simultaneously, the possibility and methods of bilateral or multilateral co-operation in utilization of research reactor, personnel and technology exchange of radioisotope production and labeling compounds is also discussed. (author)

Variations of some parameters of enzyme induction in chemical workers

Energy Technology Data Exchange (ETDEWEB)

Dolara, P. (Univ. of Florence, Italy); Lodovici, M.; Buffoni, F.; Buiatti, E.; Baccetti, S.; Ciofini, O.; Bavazzano, P.; Barchielli, S.; Vannucci, V.

1982-01-01

Several parameters related to mono-oxygenase activity were followed in a population of chemical workers and controls. Workers exposed to toluene and xylene had a significant increase of urinary glucaric acid, that was correlated with hippuric acid excretion. On the other hand, workers exposed to pigments showed a marked increase of antipyrine half-life. A dose-related decrease of liver N-demethylase was induced in rats by the administration of a mixture of three of the pigments in use in the plant. Serum gamma-glutamyltranspeptidase was decreased in the workers exposed to pigments, but this variation was not statistically significant. The exposure to different chemicals in the workplace seemed to induce a complicated variation of mono-oxygenase levels, some enzyme being inhibited and others induced in the same group of workers. The sensitivity of these workers to toxic effects of chemicals, carcinogenic compounds and drugs seems to differ markedly from the control population.

Sequential and functional renal scintiscanning in diabetic and hypertensive patients

International Nuclear Information System (INIS)

Wagner, M.

1978-01-01

47 diabetics (94 kidneys), 30 diabetics with concurrent hypertension (60 kidneys), and 23 hypertensives (46 kidneys) were examined by renal serial functional scintiscanning with 131 I-ortho-iodo-hippuric acid. For evaluation, camera nephrographs of the whole kidney, renal hemispheres, and renal cortex were used according to the technique of 'regions of interest', and the parameters of secretory value, maximum secretion, and elimination half-life were determined on this basis. With regard to the extent of hypertension, there are significant differences between all three groups for the elimination half-life; as far as the secretory value was concerned, there was a difference between the group with high hypertension and the two other groups. Significant differences in secretory value and elimination half-life were also observed in hypertensives with and without changes in the fundus of the eye. There was no noticeable difference between the three parameters in groups with and without albuminuria. (orig./AJ) 891 AJ/orig.- 892 MKO [de

Radioisotope examination of the renal function in gravidic pyelonephritis

International Nuclear Information System (INIS)

Voigt, R.; Stoll, W.; Arndt, J.

1980-01-01

By means of the results of combined renal sequence scintigraphy and 131 I-hippurate clearance in 18 pregnant women with gravidic pyelonephritis as well as in 22 voluntary healthy pregnant women of the corresponding duration of pregnancy and in 13 non-pregnant women without hormonal anticonception as control groups the detection of the renal function with the clinical picture of gravidic pyelonephritis is discussed. The clearance equivalents are represented globally as well as subdivided to the single kidney. Besides typical activity-time curves of the control groups are demonstrated. It was shown that at the time of the most frequent occurrence of gravidic pyelonephritis in the 7th-8th month of pregnancy the clearance equivalents are decreased compared to those of uncomplicated pregnancy. The changes in the course of activity-time curves manifest themselves in a decreased initial phase as well as in an increased excretory phase. Conclusions are drawn for the clinical preliminary diagnosis of risky pregnancies from the results discussed regarding further references. (author)

Mechanism of ochratoxin A transport in kidney

International Nuclear Information System (INIS)

Sokol, P.P.; Ripich, G.; Holohan, P.D.; Ross, C.R.

1988-01-01

The effect of the fungal metabolite (mycotoxin) Ochratoxin A (OTA) on the transport of p-amino[ 3 H]hippurate (PAH), a prototypic organic anion, was examined in renal brush border (BBMV) and basolateral membrane vesicles (BLMV). OTA was as effective an inhibitor of PAH uptake in both membranes as probenecid. The dose response curves for OTA in BBMV and BLMV gave IC50 values of 20 +/- 6 and 32 +/- 7 microM, respectively. The effect was specific since the transport of the organic cation N1-methylnicotinamide was not affected. The phenomenon of counterflow was studied to establish that OTA is translocated. OTA produced trans stimulation of PAH transport in both BBMV and BLMV, demonstrating that OTA is transported across both these membranes. The data suggest that OTA interacts with the PAH transport system in both BBMV and BLMV. We conclude that OTA transport in the kidney is mediated via the renal organic anion transport system

New insights into the catalytic mechanism of human glycine N-acyltransferase.

Science.gov (United States)

van der Sluis, Rencia; Ungerer, Vida; Nortje, Carla; A van Dijk, Alberdina; Erasmus, Elardus

2017-11-01

Even though the glycine conjugation pathway was one of the first metabolic pathways to be discovered, this pathway remains very poorly characterized. The bi-substrate kinetic parameters of a recombinant human glycine N-acyltransferase (GLYAT, E.C. 2.3.1.13) were determined using the traditional colorimetric method and a newly developed HPLC-ESI-MS/MS method. Previous studies analyzing the kinetic parameters of GLYAT, indicated a random Bi-Bi and/or ping-pong mechanism. In this study, the hippuric acid concentrations produced by the GLYAT enzyme reaction were analyzed using the allosteric sigmoidal enzyme kinetic module. Analyses of the initial rate (v) against substrate concentration plots, produced a sigmoidal curve (substrate activation) when the benzoyl-CoA concentrations was kept constant, whereas the plot with glycine concentrations kept constant, passed through a maximum (substrate inhibition). Thus, human GLYAT exhibits mechanistic kinetic cooperativity as described by the Ferdinand enzyme mechanism rather than the previously assumed Michaelis-Menten reaction mechanism. © 2017 Wiley Periodicals, Inc.

Microwave Assisted Condensation Reactions of 2-Aryl Hydrazonopropanals with Nucleophilic Reagents and Dimethyl Acetylenedicarboxylate

Directory of Open Access Journals (Sweden)

Rita M. Borik

2007-08-01

Full Text Available The reaction of methyl ketones 1a-g with dimethylformamide dimethylacetal (DMFDMA afforded the enaminones 2a-g, which were coupled with diazotized aromatic amines 3a,b to give the corresponding aryl hydrazones 6a-h. Condensation of compounds 6a-h with some aromatic heterocyclic amines afforded iminoarylhydrazones 9a-m. Enaminoazo compounds 12a,b could be obtained from condensation of 6c with secondary amines. The reaction of 6e,h with benzotriazolylacetone yielded 14a,b. Also, the reaction of 6a,b,d-f,h with glycine and hippuric acid in acetic anhydride afforded pyridazinone derivatives 17a-f. Synthesis of pyridazine carboxylic acid derivatives 22a,b from the reaction of 6b,e with dimethyl acetylenedicarboxylate (DMAD in the presence of triphenylphosphine at room temperature is also reported. Most of these reactions were conducted under irradiation in a microwave oven in the absence of solvent in an attempt to improve the product yields and to reduce the reaction times.

The use of portable semiconductor detectors in nuclear medicine

International Nuclear Information System (INIS)

Kuhn, W.

1986-01-01

A new biotelemetric system, CdTe semiconductor detectors with portable hard memory, for the registration of time activity curves in particular body regions of patients is introduced. The hard- and software connection of the system to the already present EDV configuration is described. The characteristics of the detectors are studied, theoretically explained and compared to the information given by the producers. By means of the determination of the ortho-iodine hippuric acid clearance (OIH) from the registration of the time activity curves in the chest the first information about the practicability in clinical use as well as the validity of the method are deduced. The detector system proved itself to be susceptible to problems, especially from manipulation of the cable or from movement of the patient. The determination of the OIH clearance from the partial body curve was problematic, because an extrapolation to the whole body based on the specific OIH kinetic in the small, observed tissue section is difficult. The comparison with the camera picture should be carefully evaluated, because this method has in principle the same inadequacies. (orig./HP) [de

Use of deuterated tyrosine and phenylalanine in the study of catecholamine and aromatic acid metabolism

International Nuclear Information System (INIS)

Curtius, H.C.; Redweik, U.; Steinmann, B.; Leimbacher, W.; Wegmann, H.

1975-01-01

Deuterated tyrosine and phenylalanine have been used for the study of their respective metabolism in patients with phenylketonuria (PKU) and in healthy persons. Urinary excretion of dopamine and its metabolites was studied by GC-MS after oral administration of deuterated L-tyrosine in 2 patients with PKU and in normal controls at low and high plasma phenylalanine levels. From these studies it seemed that the in vivo tyrosine 3-hydroxylase activity and thus the formation of L-dopa depend on the phenylalanine concentration in plasma and also in tissues. After loading 3 mentally retarded patients with 3,5-[ 2 H 2 ]-4-hydroxyphenylalanine, we found, among others, excretion of deuterated m-hydroxyphenyl-hydracrylic acid, p-hydroxymandelic acid, p-hydroxybenzoic acid, p-hydroxyhippuric acid, benzoic acid and hippuric acid. An intramolecular rearrangement is postulated. Deuterated phenylalanine was used to investigate phenylalanine and dopa metabolism in PKU. In addition, one untreated person with PKU of normal intelligence and normal excretion of catecholamines at high plasma phenylalanine concentration was investigated in order to see whether there exists an alternative metabolic pathway from phenylalanine to dopa formation

Blanching improves anthocyanin absorption from highbush blueberry ( Vaccinium corymbosum L.) purée in healthy human volunteers: a pilot study.

Science.gov (United States)

Del Bo', Cristian; Riso, Patrizia; Brambilla, Ada; Gardana, Claudio; Rizzolo, Anna; Simonetti, Paolo; Bertolo, Gianni; Klimis-Zacas, Dorothy; Porrini, Marisa

2012-09-12

Blueberries ( Vaccinium corymbosum L.) are rich sources of phenolics and anthocyanins (ACNs). We investigated the absorption of ACNs after consumption of one portion (300 g) of minimally processed blueberry purée (P) obtained from blanched (BL) or unblanched (NB) berries. A repeated-measures, crossover design study was conducted on healthy human volunteers. Blood was drawn between baseline and 24 h after BL-P or NB-P consumption, while urine were collected from the day before the experiment up to 48 h. Total plasma ACN content was not significantly different, while phenolics content was higher in BL-P with respect to NB-P. The maximum ACN absorption in plasma was observed after 1.5 h from the intake of the purées and was significantly higher (p ≤ 0.05) after the intake of BL-P. Both products increased the excretion of hippuric acid in urine. In conclusion, blanching had no significant effect on total ACN content and enhanced their absorption from minimally processed purées.

Aroma release in the oral cavity after wine intake is influenced by wine matrix composition.

Science.gov (United States)

Esteban-Fernández, Adelaida; Muñoz-González, Carolina; Jiménez-Girón, Ana; Pérez-Jiménez, María; Pozo-Bayón, María Ángeles

2018-03-15

The aim of this study has been to investigate if wine matrix composition might influence the interaction between odorants and oral mucosa in the oral cavity during a "wine intake-like" situation. Aroma released after exposing the oral cavity of three individuals to different wines (n=12) previously spiked with six target aromas was followed by an -in vivo intra-oral SPME approach. Results showed a significant effect of wine matrix composition on the intra-oral aroma release of certain odorants. Among the wine matrix parameters, phenolic compounds showed the largest impact. This effect was dependent on their chemical structure. Some phenolic acids (e.g. hippuric, caffeic) were associated to an increase in the intra-oral release of certain odorants (e.g. linalool, β-ionone), while flavonoids showed the opposite effect, decreasing the intra-oral release of aliphatic esters (ethyl hexanoate). This work shows for the first time, the impact of wine composition on oral-mucosa interactions under physiological conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Occurrence of Campylobacter species in poultry forms in Lagos area of Nigeria.

Science.gov (United States)

Aboaba, O O; Smith, S I

2005-06-01

Samples of poultry droppings were collected from fifty poultry farms in Lagos area of Nigeria. Campylobacter species were isolated from serially diluted samples using Bolton selective enrichment medium under microaerophilic condition at 42 degrees C. Samples of water, both treated and untreated used in the farms were also analysed in the same manner. Fifteen Campylobacter strains were isolated from the droppings. All the strains were identified using biochemical characteristics differentiating Campylobacter species. They were identified as hippurate positive (C. jejuni) and negative species (C. coli). They were biotype' using the extended scheme described by Lior (1984). Campylobacter coli biotype 'I was the most prevalent (66.66%) followed by C. jejuni biotype 1 (20.00%). The biotype ii of the two species accounted for 6.67% each. The C. jejuni biotype III and IV were not isolated during the study. The preponderance of C. coli indicates that poultry can be a major reservoir for the spread of human campylobacteriosis. Poultry farmers, therefore, must ensure prompt and adequate means of disposal of waste materials as well as maintaining good sanitary conditions.

Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption

Directory of Open Access Journals (Sweden)

Hyang Yeon Kim

2015-02-01

Full Text Available In this study, we investigated the clinical changes induced by a high fat diet (HFD and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs, and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND, HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS, gas chromatography (GC-TOF-MS, and linear trap quadruple mass spectrometry (LTQ-XL-MS combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling.

Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats.

Science.gov (United States)

Zhu, Lei; Zhao, Zhi Jun; Ren, Xiao Bin; Li, Qiang; Ding, Hua; Sun, Zhou; Kao, Qing Jun; Wang, Li Hua

2018-01-01

The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig

Science.gov (United States)

Kandasamy, S. B.; Williams, B. A.

1983-01-01

The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl normetazocine and an agonist at both kappa and sigma receptors, pentazocine, was found to induce hyperthermia in guinea pigs. The similar administration of peptide opioids like beta endorphin, methionine endkephalin, leucine endkephaline, and several of their synthetic analogues was also found to cause hyperthermia. Only the liver-like transport system of the three anion transport systems (iodide, hippurate, and liver-like) present in the choroid plexus was determined to be important to the central inactivation of beta-endorphin and two synthetic analogues. Prostaglandins and norepinephrine (NE) as well as cAMP were not involved in peptide and nonpeptide opioid-induced hyperthermia. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine and beta-endorphin, while hyperthermic responses to ketocyclazocine, N-allyl normetazocine, pentazocine, Met-enkephalin, Leu-enkephalin, and two of the synthetic analogues were not antagonized by nalozone. The lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP, and NE-induced hyperthermia shows that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.

Isotope nephrography in the assessment of different methods of surgical repair of the kidney after blunt lesions of intermediate degree

International Nuclear Information System (INIS)

Hoeflin, F.G.; Schoenenberger, A.; Mettler, D.; Roesler, H.; Zimmermann, A.; Bilweis, J.; Zingg, E.

1986-01-01

Despite recent improvements in diagnostic facilities there are no clear guidelines for the management of intermediate degree blunt renal trauma. Sixteen experimentally induced blunt renal lesions in pigs were treated either with a new alloplastic renal capsule made to our specifications of semi-elastic Vicryl mesh or with homologous pig fibrin sealant of with through-and-through chromic catgut sutures. Postoperative renal function was repeatedly assessed in all animals by isotope renography using 123 I-hippuric acid. Results: At surgery the Vicryl mesh was easily and quickly applied. The two other procedures were technically more demanding and time-consuming. Full haemostasis was obtained with all three methods. Kidneys which had been repaired with the Vicryl mesh contained considerably less scar tissue at the site of parenchymal rupture and showed neither perirenal fibrosis nor atrophy of the parenchyma in the vicintiy of the capsule. In a first net version, where high initial tension was applied, final clearance was significantly lower than in the other groups, due to an initial transient ischemic period. A modified technique with a second, final net version allowing controlled expansion of the kidneys during the postoperative period resulted in optimal late results. (Author)

Using NMR-Based Metabolomics to Evaluate Postprandial Urinary Responses Following Consumption of Minimally Processed Wheat Bran or Wheat Aleurone by Men and Women.

Science.gov (United States)

Garg, Ramandeep; Brennan, Lorraine; Price, Ruth K; Wallace, Julie M W; Strain, J J; Gibney, Mike J; Shewry, Peter R; Ward, Jane L; Garg, Lalit; Welch, Robert W

2016-02-17

Wheat bran, and especially wheat aleurone fraction, are concentrated sources of a wide range of components which may contribute to the health benefits associated with higher consumption of whole-grain foods. This study used NMR metabolomics to evaluate urine samples from baseline at one and two hours postprandially, following the consumption of minimally processed bran, aleurone or control by 14 participants (7 Females; 7 Males) in a randomized crossover trial. The methodology discriminated between the urinary responses of control, and bran and aleurone, but not between the two fractions. Compared to control, consumption of aleurone or bran led to significantly and substantially higher urinary concentrations of lactate, alanine, N-acetylaspartate acid and N-acetylaspartylglutamate and significantly and substantially lower urinary betaine concentrations at one and two hours postprandially. There were sex related differences in urinary metabolite profiles with generally higher hippurate and citrate and lower betaine in females compared to males. Overall, this postprandial study suggests that acute consumption of bran or aleurone is associated with a number of physiological effects that may impact on energy metabolism and which are consistent with longer term human and animal metabolomic studies that used whole-grain wheat diets or wheat fractions.

Renal function after unilateral nephrectomy for Wilms' tumour: the influence of radiation therapy

International Nuclear Information System (INIS)

Graaf, S.S.N. de; Gent, H. van; Reitsma-Bierens, W.Ch.C.; Luyk, W.H.J. van; Postma, A.; Dolsma, W.V.

1996-01-01

The effect of therapy on renal function after unilateral nephrectomy for Wilms' tumour was studied. In the second year following unilateral nephrectomy, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated simultaneously by measuring 125 I-iothalamate clearance and 131 I-hippurate clearance. Of 41 evaluable patients, 29 received chemotherapy as sole treatment modality following nephrectomy (group 1); 12 patients additionally received radiation therapy to a field that included the remaining kidney (group 2). Results were expressed as standard deviation scores (z-scores). In group 1, mean z-score for GFR was -0.27 (94.6% of normal) and in group 2 mean z-score was -1.51 (72.7% of normal for two kidneys) (P = 0.022, Mann-Whitney U-test). Mean z-score for ERPF was -0.09 (97.0%) in group 1 and -1.53 (73.8%) in group 2 (P 0.039). It was concluded that the combination of chemotherapy and radiation therapy, in contrast to chemotherapy alone, negatively affects the ability of the remaining kidney to adjust its function after the loss of its counterpart. (author)

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction.

Science.gov (United States)

Naidoo, V; Swan, G E

2009-04-01

Diclofenac (DF), a non-steroidal anti-inflammatory drug (NSAID), is largely regarded as one of the most devastating environmental toxicant in recent times, after accidental exposure via their food-chain lead to massive mortalities in three vulture species on the Asian subcontinent. Although the use of diclofenac was recently banned on the Indian subcontinent, following the favourable safety profile of meloxicam, its mechanism of toxicity remains unknown. In an attempt to establish this mechanism, we test three hypotheses using models established from either the domestic chicken (Gallus domesticus) or the African White-backed vulture (Gyps africanus). We demonstrate that both DF and meloxicam are toxic to renal tubular epithelial (RTE) cells following 12 h of exposure, due to an increase in production of reactive oxygen species (ROS), which could be temporarily ameliorated by pre-incubation with uric acid (UA). When cultures were incubated with either drug for only 2 h, meloxicam showed no toxicity in contrast to diclofenac. In both cases no increase in ROS production was evident. In addition, diclofenac decreased the transport of uric acid, by interfering with the p-amino-hippuric acid (PAH) channel. We conclude that vulture susceptibility to diclofenac results from a combination of an increased ROS, interference with UA transport and the duration of exposure.

Urinary Metabolite Profiling Offers Potential for Differentiation of Liver-Kidney Yin Deficiency and Dampness-Heat Internal Smoldering Syndromes in Posthepatitis B Cirrhosis Patients

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Xiaoning Wang

2015-01-01

Full Text Available Zheng is the basic theory and essence of traditional Chinese medicine (TCM in diagnosing diseases. However, there are no biological evidences to support TCM Zheng differentiation. In this study we elucidated the biological alteration of cirrhosis with TCM “Liver-Kidney Yin Deficiency (YX” or “Dampness-Heat Internal Smoldering (SR” Zheng and the potential of urine metabonomics in TCM Zheng differentiation. Differential metabolites contributing to the intergroup variation between healthy controls and liver cirrhosis patients were investigated, respectively, and mainly participated in energy metabolism, gut microbiota metabolism, oxidative stress, and bile acid metabolism. Three metabolites, aconitate, citrate, and 2-pentendioate, altered significantly in YX Zheng only, representing the abnormal energy metabolism. Contrarily, hippurate and 4-pyridinecarboxylate altered significantly in SR Zheng only, representing the abnormalities of gut microbiota metabolism. Moreover, there were significant differences between two TCM Zhengs in three metabolites, glycoursodeoxycholate, cortolone-3-glucuronide, and L-aspartyl-4-phosphate, among all differential metabolites. Metabonomic profiling, as a powerful approach, provides support to the understanding of biological mechanisms of TCM Zheng stratification. The altered urinary metabolites constitute a panel of reliable biological evidence for TCM Zheng differentiation in patients with posthepatitis B cirrhosis and may be used for the potential biomarkers of TCM Zheng stratification.

An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

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Gooda Sahib Jambocus, Najla; Saari, Nazamid; Ismail, Amin; Mahomoodally, Mohamad Fawzi; Abdul Hamid, Azizah

2016-01-01

The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a 1H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment. PMID:26798649

Impact of coexposure on toluene biomarkers in rats.

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Cosnier, Frédéric; Nunge, Hervé; Brochard, Céline; Burgart, Manuella; Rémy, Aurélie; Décret, Marie-Josèphe; Cossec, Benoît; Campo, Pierre

2014-03-01

1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of these biomarkers may depend on factors potentially interfering with TOL biotransformation, such as the presence of other solvents in the workplace. Mercapturic acids (MAs) could be an alternative to the "traditional" TOL biomarkers. 2. This study aims (1) to investigate in rat the effects of an exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well MAs performed in these contexts compared to the traditional TOL biomarkers. 3. Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH), ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological exposure indicators were then measured. 4. Depending on the compounds in the mixture and their concentrations, TOL metabolism was accelerated (with BuOH), unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an increase in blood TOL concentrations, even at authorized atmospheric concentrations, which may potentiate the effect of TOL. 5. MAs excretions are little affected by coexposure scenarios, their levels correlating well with atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric TOL exposure.

An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

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Najla Gooda Sahib Jambocus

2016-01-01

Full Text Available The prevalence of obesity is increasing worldwide, with high fat diet (HFD as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60. After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a 1H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate, amino acid metabolism (alanine, 2-hydroxybutyrate, choline metabolism (betaine, creatinine metabolism (creatinine, and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline. Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment.

Effect of pistachio consumption on the modulation of urinary gut microbiota-related metabolites in prediabetic subjects.

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Hernández-Alonso, Pablo; Cañueto, Daniel; Giardina, Simona; Salas-Salvadó, Jordi; Cañellas, Nicolau; Correig, Xavier; Bulló, Mònica

2017-07-01

The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Nuclear magnetic resonance (NRM) was performed to determine changes in 24-h urine metabolites. Significant changes in urine metabolites according to the different intervention periods were found in uni- and multivariate analysis. Score plot of the first two components of the multilevel partial least squares discriminant analysis (ML-PLS-DA) showed a clear separation of the intervention periods. Three metabolites related with gut microbiota metabolism (i.e., hippurate, p-cresol sulfate and dimethylamine) were found decreased in PD compared with CD (Ppistachio consumption may modulate some urinary metabolites related to gut microbiota metabolism and the TCA cycle; all associated with metabolic derangements associated with insulin resistance and Type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Concentrations of Environmental Chemicals in Urine and Blood Samples of Children from San Luis Potosí, Mexico.

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Perez-Maldonado, Ivan N; Ochoa-Martinez, Angeles C; Orta-Garcia, Sandra T; Ruiz-Vera, Tania; Varela-Silva, Jose A

2017-08-01

Human biomonitoring (HBM) is an appreciated tool used to evaluate human exposure to environmental, occupational or lifestyle chemicals. Therefore, the aim of this study was to evaluate the exposure levels for environmental chemicals in urine and blood samples of children from San Luis Potosí, Mexico (SLP). This study identifies environmental chemicals of concern such as: arsenic (45.0 ± 15.0 µg/g creatinine), lead (5.40 ± 2.80 µg/dL), t,t-muconic acid (266 ± 220 µg/g creatinine), 1-hydroxypyrene (0.25 ± 0.15 µmol/mol creatinine), PBDEs (28.0 ± 15.0 ng/g lipid), and PCBs (33.0 ± 16.0 ng/g lipid). On the other hand, low mercury (1.25 ± 1.00 µg/L), hippuric acid (0.38 ± 0.15 µg/g creatinine) and total DDT (130 ± 35 ng/g lipid) exposure levels were found. This preliminary study showed the tool's utility, as the general findings revealed chemicals of concern. Moreover, this screening exhibited the need for HBM in the general population of SLP.

Structurally modified fatty acids - clinical potential as tracers of metabolism

International Nuclear Information System (INIS)

Dudczak, R.; Schmoliner, R.; Angelberger, P.; Knapp, F.F.; Goodman, M.M.

1985-01-01

Recently 15-p-iodophenyl-betamethyl-pentadecanoic acid (BMPPA) was proposed for myocardial scintigraphy, as possible probe of metabolic processes other than β-oxidation. In 19 patients myocardial scintigraphy was done after i.v. BMPPA (2 to 4 mCi). Data were collected (LAO 45 0 /14; anterior/5) for 100 minutes in the fasted patients. From heart (H) and liver (L) organ to background (BG) ratios were calculated, and the elimination (E) behavior was analyzed from BG (V. cava region) corrected time activity curves. In 10 patients plasma and urine were examined. By CHCl 3 /MeOH extraction of plasma samples (90 min. pi) both in water and in organic medium soluble catabolites were found. TLC fractionation showed that those were co-migrating, compared to standards, with benzoic acid, BMPPA and triglycerides. In urine (0 to 2h pi: 4.1% dose) hippuric acid was found. It is concluded that BMPPA is a useful agent for myocardial scintigraphy. Its longer retention in the heart compared to unbranched radioiodinated fatty acids may facilitate SPECT studies. Rate of elimination and plasma analysis indicate the metabolic breakdown of BMPPA. Yet, the complexity of the supposed mechanism may impede curve interpretation in terms of specific metabolic pathways. 19 refs., 5 tabs

Mediterranean Diet Score: Associations with Metabolic Products of the Intestinal Microbiome, Carotid Plaque Burden, and Renal Function

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Michael Pignanelli

2018-06-01

Full Text Available Metabolic products of the intestinal microbiome such as trimethylamine N-oxide (TMAO that accumulate in renal failure (gut-derived uremic toxins, GDUTs affect atherosclerosis and increase cardiovascular risk. We hypothesized that patients on a Mediterranean diet and those consuming lower amounts of dietary precursors would have lower levels of GDUTs. Patients attending vascular prevention clinics completed a Harvard Food Frequency Questionnaire (FFQ and had plasma levels of TMAO, p-cresylsulfate, hippuric acid, indoxyl sulfate, p-cresyl glucuronide, phenyl acetyl glutamine, and phenyl sulfate measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Carotid plaque burden was measured by ultrasound; CKD-Epi equations were used to estimate the glomerular filtration rate. In total, 276 patients completed the study. Even moderate renal function significantly increased plasma GDUTs, which were significantly associated with higher carotid plaque burden. There was no significant difference in plasma levels of any GDUT associated with a Mediterranean diet score or with intake of dietary precursors. In omnivorous patients with vascular disease, the intake of dietary precursors of intestinal metabolites or adherence to a Mediterranean diet did not change plasma GDUT. Approaches other than diet, such as probiotics and repopulation of the intestinal microbiome, may be required to mitigate the adverse effects of GDUTs.

The juniper bush of autism spectrum disorder (ASD: metabolomics, microbiomics, acetaminophen. What else?

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Vassilios Fanos

2018-05-01

. By using 1H NMR spectroscopy, our group found a combination of increased and decreased concentrations of: hippurate, glycine, creatine, tryptophan, D-threitol, and glutamate, creatinine, lactate, valine, betaine, and taurine, respectively. These findings strongly suggest a crucial role of oxidative stress and gut microflora in ASD development. In children with ASD, gut dysbiosis is characterized by the increase in Clostridium, Alistipes, Akkermansia, Caloramator, Sarcina spp., and by the reduction in Prevotella spp., E. siraeum, and Bifidobacterium spp. As a result, in these children the urine metabolome is marked by alterations in hippuric acid, p-hydroxyphenylacetic acid and 3-(3-hydroxyphenyl-3-hydroxypropanoic acid concentration. Moreover, propionic acid, related to Clostridium spp. is strongly involved. Metabolomics can lead to the discovery of dozens of biomarkers strongly implicated in the pathogenesis of ASD (i.e. mannitol, L-threonic acid, fucose, glycine, serine, and many others. Finally, the potential toxicity of acetaminophen (paracetamol, a very common analgesic and antipyretic drug widely used during pregnancy, after birth and in early childhood should be carefully considered in combination with the microbiome.

Pea fiber and wheat bran fiber show distinct metabolic profiles in rats as investigated by a 1H NMR-based metabolomic approach.

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Guangmang Liu

Full Text Available This study aimed to examine the effect of pea fiber (PF and wheat bran fiber (WF supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-ketoglutarate. However, PF significantly decreased the plasma levels of isoleucine, leucine, lactate, and pyruvate as well as the urine levels of allantoin, bile acids, and trigonelline. WF significantly increased the plasma levels of acetone, isobutyrate, lactate, myo-inositol, and lipids as well as the urine levels of alanine, lactate, dimethylglycine, N-methylniconamide, and α-ketoglutarate. However, WF significantly decreased the plasma levels of amino acids, and glucose as well as the urine levels of acetate, allantoin, citrate, creatine, hippurate, hydroxyphenylacetate, and trigonelline. Results suggest that PF and WF exposure can promote antioxidant activity and can exhibit common systemic metabolic changes, including lipid metabolism, energy metabolism, glycogenolysis and glycolysis metabolism, protein biosynthesis, and gut microbiota metabolism. PF can also decrease bile acid metabolism. These findings indicate that different fiber diet may cause differences in the biofluid profile in rats.

Metabonomics-Based Study of Clinical Urine Samples in Suboptimal Health with Different Syndromes

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Hai-Zhen Cui

2013-01-01

Full Text Available Objective. To explore the urinary biochemistry features of syndromes of traditional Chinese medicine (TCM such as syndrome of stagnation of liver Qi, spleen deficiency, liver Qi stagnation, and spleen deficiency (LSSDS in sub-optimal health status (SHS. Methods. 12 cases for each syndrome group in SHS were selected, 12 subjects were used as a normal control group, and 1H NMR detection was, respectively, carried out, and the data was corrected by the orthogonal signal correction (OSC and then adopted a partial least squares (PLS method for discriminate analysis. Results. The OSC-PLS (ctr analysis results of the nuclear overhauser enhancement spectroscopy (NOESY detection indicated that the syndromes in SHS could be differentiated, and there were significant differences in the levels of metabolites of the urine samples of the four groups; the biomarkers of LSSDS in SHS were found out. The contents of citric acid (2.54 and 2.66, trimethylamineoxide (3.26, and hippuric acid (3.98, 7.54, 7.58, 7.62, 7.66, 7.82, and 7.86 in the urine samples of LSSDS group were lower than that of the normal control group. Conclusion. There are differences in the 1H-NMR metabolic spectrum of the urine samples of the four groups, and the specific metabolic products of the LSSDS in SHS can be identified from metabonomics analysis.

Radioisotope production

International Nuclear Information System (INIS)

1988-01-01

The trial production runs started in the previous report period were continued and have been extended to 67 Ga, 81 Rb/ 81m Kr and 111 In, the production of which will be taken over from the Pretoria cyclotron at the end of this year, when that machine is scheduled to be shut down. After commissioning of the target water cooling system and the helium cooling system for beam foil windows at the beginning of this year, these production runs could also be extended to high beam currents (up to 50 μA). Test consignments of a number of products have been supplied to various potential future users, and 123 I, in the form of Na 123 I capsules as well as 123 I-sodium hippurate, and 52 Fe-citrate have actually been used with success in trial diagnostic studies on patients. A procedure for labelling IPPA and 3-IPMPA with 123 I has been developed, while initial work has also been done on the radioiodination of monoclonal antifibrine antibodies. The last major facility needed for the commencement of the routine radioisotope production programme, namely the multiple-target facility, is now ready for installation in the production vault within the next few weeks, and routine production runs are expected to start in November 1988. 4 figs., 18 refs

Prevalence and Distribution of Campylobacter jejuni in Small-Scale Broiler Operations.

Science.gov (United States)

Tangkham, Wannee; Janes, Marlene; LeMieux, Frederick

2016-01-01

Campylobacter jejuni has been recognized as one of the most prevalent causes of foodborne bacterial illnesses in humans. Previous studies have focused on the transmission routes of C. jejuni from commercial flock farms to the final retail product. The objective of this study was to determine the prevalence of C. jejuni and Campylobacter spp. in eggshells, live birds, feed, drinking water, and the rearing environment in a small-scale broiler operation. Broilers were raised under two different production systems: (i) environmentally controlled housing and (ii) open-air housing with two replications. Each week, samples were collected from eggshells, bird feces, feed, drinking water, enclosures (vertical walls of bird housing), and feed troughs for enumeration and isolation testing. All samples were plated on modified charcoal-cefoperazone-deoxycholate agar to determine the log CFU per gram and percent prevalence of Campylobacter spp. Isolation of C. jejuni was verified with latex agglutination and hippurate hydrolysis tests. The results from this study suggest that vertical transmission of these bacteria from egg surfaces to newly hatched chicks is not a significant risk factor. The results also suggest that the prevalence of C. jejuni at time of harvest (week 6) was significantly higher (P < 0.05) in the open-air housing broilers than in those in the environmentally controlled housing. Elevated levels of cross-contaminants, especially water and feed, may have played a role in this outcome.

Professor Rastislav Dzúrik: the Man and the Scientist.

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Derzsiová, Katarina; Mydlík, Miroslav

2016-02-01

Rastislav Dzrik, finished his medical study at the Medical School of Comenius University in Bratislava in 1953. After graduation he began to work at the Institute of chemistry and biochemistry of the Medical School and in 1957 he continued working at the IIIrd Internal Clinic of this faculty, which became later the base of "Internal School of Professor T. R. Niederland" with biochemical focusing. In the year 1967 ProfessorDzrik in cooperation with ProfessorJan Brod founded the Nephrological Section of the Slovak Internal Society and then the postgraduate scientific-research activity in nephrology began. The main topics of his scientific activity, in which he received many priority results, were: Isolation and characteristic of inhibitor of glucose utilisation and of inhibitor of renal gluconeogenesis; Effect of "middle molecular substances, especially in the development of renal insufficiency; Isolation and identification of hippurate and pseudouridine. His publishing activity was manifested in more than 500 scientific papers, several monographs and many chapters in various textbooks and manuals of internal medicine and clinical biochemistry, and more than 1,000 citations. The most important success of Professor Dzrik was the textbook "Nephrology which was published in 2004 and he was its main editor. Rastislav Dzriks impact on the field of Nephrology in Slovakia was manifold. It included his complex work of clinical nephrology, his pedagogical activities, and last but not least his excellent organizing abilities.

Liver function in patients exposed to a toluene in a hydrocarbon processing plant

International Nuclear Information System (INIS)

Sanchez, E; Fernandez D'Pool, J.

1996-01-01

Since the hepatotoxic role of toluene in exposed workers from the petroleum and petrochemical industries chronically exposed to low concentration has no been entirely dilucidated, this transversal study was undertaken in order to clarify the situation in the local industries. A group of 33 non-exposed men workers of such industries (group control, aged 33.0 +/- 4.88 years) were compared with 33 toluene-exposed men (aged 35.0 +/- 9.33 years) from the related industries, with a minimal of 6 months exposition time to toluene and without liver disease history. In addition to a complete occupational diseases medical history, each subject was tested by both a venous blood sample (to determine prothrombin, total and fractioned bilirubin, total and fractioned proteins, liver enzymes and cholesterol) and urine sample (hippuric acid). Also the environmental concentration of toluene in working areas was determined by gas chromatography, which was below the recommended standard levels in working areas. Although the analyzed parameters were in the normal range, it was observed that those workers with known alcohol ingestion and toluene exposition had several abnormalities. The results of this study confirm that toluene may have a synergistic hepatotoxic effect in toluene-exposed workers that are alcohol consumers. The alcohol in considered as a confounding factor and it is not possible to rule out in the etiology of hepatic changes detected in the study

Chinese medicinal formula Fufang Xueshuantong capsule could inhibit the activity of angiotensin converting enzyme

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Sheng, Shujing; Wang, Yonggang; Long, Chaofeng; Su, Weiwei; Rong, Xia

2014-01-01

Fufang Xueshuantong (FXST) capsule, a Chinese medicinal formula composed of four herbals – Panax notoginseng, Radix Astragali, Radix Salvia Miltiorrhizae and Radix Scrophulariaceae, has been used to treat cardiovascular diseases for many years, but the pharmacological mechanisms underlying its effects has not been clarified. This study investigates if a connection between FXST and angiotensin converting enzyme (ACE) might be an explanation for its pharmacological effects. ACE inhibition assay was performed on FXST capsule, 50% ethanol extracts from the four herbals and three selected saponins most abundant in P. notoginseng (Ginsenoside Rg1, Ginsenoside Rb1 and Notoginsenoside R1) using a biochemical test. Reversed-phase high-performance liquid chromatography of liberated hippuric acid from the ACE assay was conducted to determine the inhibitory effect. As a result, FXST and extracts from P. notoginseng showed a significant and dose-dependent inhibition on ACE activity with the IC50 values of 115 μg/ml and 179 μg/ml, respectively. But extracts from the other three herbals and the three selected saponins had no significant effect on ACE inhibition. Compared to other reported plant extracts, FXST could be considered as an effective ACE inhibitor. The inhibition of ACE activity supports the traditional use of FXST on blood circulation and the inhibitory property of FXST is mainly caused by P. notoginseng. PMID:26019516

Appraisal of the renal function in health donors of the Specialities Hospital Centro Medico La Raza, IMSS

International Nuclear Information System (INIS)

Llanos O, S.V.

2004-01-01

The techniques of Nuclear Medicine (MN) represent the most reliable and sure forms in measurement of the glomeruli filtrate (FG) and of the effective renal plasmatic flow (FPRE), by means of a simple, practical, innocuous and economic method that doesn't require urine gathering, available in the services of (MN). The renal gamma gram is at the moment the election procedure in the diagnosis and evaluation of diverse nephro urological pathologies since it provides objective information of the renal function as well as of the characteristics of the drainage of the urinal tract. They provide to the clinical doctor a real measurement of the state of the purifying renal function. their determinations are not affected by the habitual protein ingesta, they can be made with any level of seric creatinine, the exercise, size, sex. Their methodology uses the unique injection technique for each one, in which the renal purification is determined by means of Gary Gates method and the tubular secretion by based on the method of Schlegel. These techniques show a very high correlation coefficient with those standard of gold and they lack the inherent inconveniences to the technique of urine gathering. The used radiopharmaceuticals are diethylen triamine penta acetic-Tc 99m acid and Orto iodine hippurate- I 131 the only requirement for the realization of the study is an appropriate hydration (10-15 ml/Kg is calculated.) (Author)

Legionella cardiaca sp. nov., isolated from a case of native valve endocarditis in a human heart

Science.gov (United States)

Pearce, Meghan M.; Theodoropoulos, Nicole; Mandel, Mark J.; Brown, Ellen; Reed, Kurt D.

2012-01-01

A Gram-negative, rod-shaped bacterium, designated H63T, was isolated from aortic valve tissue of a patient with native valve endocarditis. 16S rRNA gene sequencing revealed that H63T belongs to the genus Legionella, with its closest neighbours being the type strains of Legionella brunensis (98.8 % similarity), L. londiniensis (97.0 %), L. jordanis (96.8 %), L. erythra (96.2 %), L. dresdenensis (96.0 %) and L. rubrilucens, L. feeleii, L. pneumophila and L. birminghamensis (95.7 %). DNA–DNA hybridization studies yielded values of Legionella. H63T was distinguishable from its neighbours based on it being positive for hippurate hydrolysis. H63T was further differentiated by its inability to grow on BCYE agar at 17 °C, its poor growth on low-iron medium and the absence of sliding motility. Also, H63T did not react with antisera generated from type strains of Legionella species. H63T replicated within macrophages. It also grew in mouse lungs, inducing histopathological evidence of pneumonia and dissemination to the spleen. Together, these results confirm that H63T represents a novel, pathogenic Legionella species, for which the name Legionella cardiaca sp. nov. is proposed. The type strain is H63T ( = ATCC BAA-2315T  = DSM 25049T  = JCM 17854T). PMID:22286905

Pressure-assisted introduction of urine samples into a short capillary for electrophoretic separation with contactless conductivity and UV spectrometry detection.

Science.gov (United States)

Makrlíková, Anna; Opekar, František; Tůma, Petr

2015-08-01

A computer-controlled hydrodynamic sample introduction method has been proposed for short-capillary electrophoresis. In the method, the BGE flushes sample from the loop of a six-way sampling valve and is carried to the injection end of the capillary. A short pressure impulse is generated in the electrolyte stream at the time when the sample zone is at the capillary, leading to injection of the sample into the capillary. Then the electrolyte flow is stopped and the separation voltage is turned on. This way of sample introduction does not involve movement of the capillary and both of its ends remain constantly in the solution during both sample injection and separation. The amount of sample introduced to the capillary is controlled by the duration of the pressure pulse. The new sample introduction method was tested in the determination of ammonia, creatinine, uric acid, and hippuric acid in human urine. The determination was performed in a capillary with an overall length of 10.5 cm, in two BGEs with compositions 50 mM MES + 5 mM NaOH (pH 5.1) and 1 M acetic acid + 1.5 mM crown ether 18-crown-6 (pH 2.4). A dual contactless conductivity/UV spectrometric detector was used for the detection. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis

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Olivier Deltombe

2015-09-01

Full Text Available As protein binding of uremic toxins is not well understood, neither in chronic kidney disease (CKD progression, nor during a hemodialysis (HD session, we studied protein binding in two cross-sectional studies. Ninety-five CKD 2 to 5 patients and ten stable hemodialysis patients were included. Blood samples were taken either during the routine ambulatory visit (CKD patients or from blood inlet and outlet line during dialysis (HD patients. Total (CT and free concentrations were determined of p-cresylglucuronide (pCG, hippuric acid (HA, indole-3-acetic acid (IAA, indoxyl sulfate (IS and p-cresylsulfate (pCS, and their percentage protein binding (%PB was calculated. In CKD patients, %PB/CT resulted in a positive correlation (all p < 0.001 with renal function for all five uremic toxins. In HD patients, %PB was increased after 120 min of dialysis for HA and at the dialysis end for the stronger (IAA and the highly-bound (IS and pCS solutes. During one passage through the dialyzer at 120 min, %PB was increased for HA (borderline, IAA, IS and pCS. These findings explain why protein-bound solutes are difficult to remove by dialysis: a combination of the fact that (i only the free fraction can pass the filter and (ii the equilibrium, as it was pre-dialysis, cannot be restored during the dialysis session, as it is continuously disturbed.

Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry

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Rodrigo P. Feliciano

2016-08-01

Full Text Available Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (polyphenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (polyphenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%–48% in plasma and 47%–54% in urine. Taken together, our results illustrate that blueberry (polyphenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

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Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

2016-08-09

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Alteration of metabolomic markers of amino-acid metabolism in piglets with in-feed antibiotics.

Science.gov (United States)

Mu, Chunlong; Yang, Yuxiang; Yu, Kaifan; Yu, Miao; Zhang, Chuanjian; Su, Yong; Zhu, Weiyun

2017-04-01

In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets.

Plasma and Urinary Phenolic Profiles after Acute and Repetitive Intake of Wild Blueberry.

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Feliciano, Rodrigo P; Istas, Geoffrey; Heiss, Christian; Rodriguez-Mateos, Ana

2016-08-25

Recent studies have shown that blueberries may have cardiovascular and cognitive health benefits. In this work, we investigated the profile of plasma and urine (poly)phenol metabolites after acute and daily consumption of wild blueberries for 30 days in 18 healthy men. The inter-individual variability in plasma and urinary polyphenol levels was also investigated. Blood samples were collected at baseline and 2 h post-consumption on day 1 and day 30. Twenty-four-hour urine was also collected on both days. A total of 61 phenolic metabolites were quantified in plasma at baseline, of which 43 increased after acute or chronic consumption of blueberries over one month. Benzoic and catechol derivatives represented more than 80% of the changes in phenolic profile after 2 h consumption on day 1, whereas hippuric and benzoic derivatives were the major compounds that increased at 0 and 2 h on day 30, respectively. The total (poly)phenol urinary excretion remained unchanged after 30 days of wild blueberry intake. The inter-individual variability ranged between 40%-48% in plasma and 47%-54% in urine. Taken together, our results illustrate that blueberry (poly)phenols are absorbed and extensively metabolized by phase II enzymes and by the gut microbiota, leading to a whole array of metabolites that may be responsible for the beneficial effects observed after blueberry consumption.

Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

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Hitoshi Uchiyama

2014-09-01

Full Text Available The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF. Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated. In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated. However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated. These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers.

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Vauzour, David; Houseman, Emily J; George, Trevor W; Corona, Giulia; Garnotel, Roselyne; Jackson, Kim G; Sellier, Christelle; Gillery, Philippe; Kennedy, Orla B; Lovegrove, Julie A; Spencer, Jeremy P E

2010-04-01

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

NMR analysis of male fathead minnow urinary metabolites: A potential approach for studying impacts of chemical exposures

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Ekman, D.R. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States)], E-mail: ekman.drew@epa.gov; Teng, Q. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States); Jensen, K.M.; Martinovic, D.; Villeneuve, D.L.; Ankley, G.T. [Mid-Continent Ecology Division, U.S. EPA, 6201 Congdon Boulevard, Duluth, MN 55804 (United States); Collette, T.W. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States)

2007-11-30

The potential for profiling metabolites in urine from male fathead minnows (Pimephales promelas) to assess chemical exposures was explored using nuclear magnetic resonance (NMR) spectroscopy. Both one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy was used for the assignment of metabolites in urine from unexposed fish. Because fathead minnow urine is dilute, we lyophilized these samples prior to analysis. Furthermore, 1D {sup 1}H NMR spectra of unlyophilized urine from unexposed male fathead minnow and Sprague-Dawley rat were acquired to qualitatively compare rat and fish metabolite profiles and to provide an estimate of the total urinary metabolite pool concentration difference. As a small proof-of-concept study, lyophilized urine samples from male fathead minnows exposed to three different concentrations of the antiandrogen vinclozolin were analyzed by 1D {sup 1}H NMR to assess exposure-induced changes. Through a combination of principal components analysis (PCA) and measurements of {sup 1}H NMR peak intensities, several metabolites were identified as changing with statistical significance in response to exposure. Among those changes occurring in response to exposure to the highest concentration (450 {mu}g/L) of vinclozolin were large increases in taurine, lactate, acetate, and formate. These increases coincided with a marked decrease in hippurate, a combination potentially indicative of hepatotoxicity. The results of these investigations clearly demonstrate the potential utility of an NMR-based approach for assessing chemical exposures in male fathead minnow, using urine collected from individual fish.

Application of {sup 1}H-NMR-based metabolomics for detecting injury induced by long-term microwave exposure in Wistar rats' urine

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Wang, Li-Feng; Peng, Rui-Yun; Wang, Shui-Ming; Gao, Ya-Bing; Dong, Ji; Zhao, Li; Li, Xiang; Zuo, Hong-Yan; Wang, Chang-Zhen [Beijing Institute of Radiation Medicine, Laboratory of Pathology, Beijing (China); Hu, Xiang-Jun [Beijing Institute of Radiation Medicine, Beijing (China); Gao, Rong-Lian [Beijing Institute of Radiation Medicine, Laser Medicine, Beijing (China); Su, Zhen-Tao [Beijing Institute of Radiation Medicine, Radiation Protection, Beijing (China); Feng, Xin-Xing [Chinese Academy of Medical Sciences, Endocrine and Cardiovascular Center, Fuwai Hospital and Cardiovascular Institute, Beijing (China)

2012-07-15

There has been growing public concern regarding exposure to microwave fields as a potential human health hazard. This study aimed to identify sensitive biochemical indexes for the detection of injury induced by microwave exposure. Male Wistar rats were exposed to microwaves for 6 min per day, 5 days per week over a period of 1 month at an average power density of 5 mW/cm{sup 2} (specific absorption rate of 2.1 W/kg). Urine specimens were collected over 24 h in metabolic cages at 7 days, 21 days, 2 months, and 6 months after exposure. {sup 1}H NMR spectroscopy data were analyzed using multivariate statistical techniques. Urine metabolic profiles of rats after long-term microwave exposure were significantly differentiated from those of sham-treated controls using principal component analysis or partial least squares discriminant analysis. Significant differences in low molecular weight metabolites (acetate, succinate, citrate, ketoglutarate, glucose, taurine, phenylalanine, tyrosine, and hippurate) were identified in the 5 mW/cm{sup 2} microwave exposure group compared with the sham-treated controls at 7 days, 21 days, and 2 months. Metabolites returned to normal levels by 6 months after exposure. These data indicated that these metabolites were related to the perturbations of energy metabolism particularly in the tricarboxylic acid cycle, and the metabolism of amino acids, monoamines, and choline in urine represent potential indexes for the detection of injury induced by long-term microwave exposure. (orig.)

Three-phase molecularly imprinted sol-gel based hollow fiber liquid-phase microextraction combined with liquid chromatography-tandem mass spectrometry for enrichment and selective determination of a tentative lung cancer biomarker.

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Moein, Mohammad Mahdi; Javanbakht, Mehran; Karimi, Mohammad; Akbari-Adergani, Behrouz; Abdel-Rehim, Mohamed

2015-07-15

In the present study, the modification of a polysulfone hollow fiber membrane with in situ molecularly imprinted sol-gel process (as a novel and one-step method) was prepared and investigated. 3-(propylmethacrylate)trimethoxysilane (3PMTMOS) as an inorganic precursor was used for preparation of molecularly imprinted sol-gel. The modified molecularly imprinted sol-gel hollow fiber membrane (MSHM) was used for the liquid-phase microextraction (LPME) of hippuric acid (HA) in human plasma and urine samples. MSHM as a selective, robust, and durable tool was used for at least 50 extractions without significant decrease in the extraction efficiency. The non-molecularly imprinted sol-gel hollow fiber membrane (NSHM) as blank hollow fiber membrane was prepared by the same process, only without HA. To achieve the best condition, influential parameters on the extraction efficiency were thoroughly investigated. The capability of this robust, green, and simple method for extraction of HA was successfully accomplished with LC/MS/MS. The limits of detection (LOD) and quantification (LOQ) in human plasma and urine samples were 0.3 and 1.0nmolL(-1), respectively. The standard calibration curves were obtained within the concentration range 1-2000nmolL(-1) for HA in human plasma and urine. The coefficients of determination (r(2)) were ≥0.998. The obtained data exhibited recoveries were higher than 89% for the extraction of HA in human plasma and urine samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Variation in antibiotic-induced microbial recolonization impacts on the host metabolic phenotypes of rats.

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Swann, Jonathan R; Tuohy, Kieran M; Lindfors, Peter; Brown, Duncan T; Gibson, Glenn R; Wilson, Ian D; Sidaway, James; Nicholson, Jeremy K; Holmes, Elaine

2011-08-05

The interaction between the gut microbiota and their mammalian host is known to have far-reaching consequences with respect to metabolism and health. We investigated the effects of eight days of oral antibiotic exposure (penicillin and streptomycin sulfate) on gut microbial composition and host metabolic phenotype in male Han-Wistar rats (n = 6) compared to matched controls. Early recolonization was assessed in a third group exposed to antibiotics for four days followed by four days recovery (n = 6). Fluorescence in situ hybridization analysis of the intestinal contents collected at eight days showed a significant reduction in all bacterial groups measured (control, 10(10.7) cells/g feces; antibiotic-treated, 10(8.4)). Bacterial suppression reduced the excretion of mammalian-microbial urinary cometabolites including hippurate, phenylpropionic acid, phenylacetylglycine and indoxyl-sulfate whereas taurine, glycine, citrate, 2-oxoglutarate, and fumarate excretion was elevated. While total bacterial counts remained notably lower in the recolonized animals (10(9.1) cells/g faeces) compared to the controls, two cage-dependent subgroups emerged with Lactobacillus/Enterococcus probe counts dominant in one subgroup. This dichotomous profile manifested in the metabolic phenotypes with subgroup differences in tricarboxylic acid cycle metabolites and indoxyl-sulfate excretion. Fecal short chain fatty acids were diminished in all treated animals. Antibiotic treatment induced a profound effect on the microbiome structure, which was reflected in the metabotype. Moreover, the recolonization process was sensitive to the microenvironment, which may impact on understanding downstream consequences of antibiotic consumption in human populations.

(1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors.

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Vázquez-Fresno, Rosa; Llorach, Rafael; Alcaro, Francesca; Rodríguez, Miguel Ángel; Vinaixa, Maria; Chiva-Blanch, Gemma; Estruch, Ramon; Correig, Xavier; Andrés-Lacueva, Cristina

2012-08-01

Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100mL/day, alcohol control). After each period, 24-h urine samples were collected and analyzed by (1) H-NMR. According to the results of a one-way ANOVA, significant markers were grouped in four categories: alcohol-related markers (ethanol); gin-related markers; wine-related markers; and gut microbiota markers (hippurate and 4-hydroxphenylacetic acid). Wine metabolites were classified into two groups; first, metabolites of food metabolome: tartrate (RWA and RWD), ethanol, and mannitol (RWA); and second, biomarkers that relates to endogenous modifications after wine consumption, comprising branched-chain amino acid (BCAA) metabolite (3-methyl-oxovalerate). Additionally, a possible interaction between alcohol and gut-related biomarkers has been identified. To our knowledge, this is the first time that this approach has been applied in a nutritional intervention with red wine. The results show the capacity of this approach to obtain a comprehensive metabolome picture including food metabolome and endogenous biomarkers of moderate wine intake. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

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Tyagi, Ritu; Rana, Poonam; Khan, Ahmad Raza; Bhatnagar, Deepak; Devi, M Memita; Chaturvedi, Shubhra; Tripathi, Rajendra P; Khushu, Subash

2011-10-01

Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity. Copyright © 2011 John Wiley & Sons, Ltd.

NMR analysis of male fathead minnow urinary metabolites: A potential approach for studying impacts of chemical exposures

International Nuclear Information System (INIS)

Ekman, D.R.; Teng, Q.; Jensen, K.M.; Martinovic, D.; Villeneuve, D.L.; Ankley, G.T.; Collette, T.W.

2007-01-01

The potential for profiling metabolites in urine from male fathead minnows (Pimephales promelas) to assess chemical exposures was explored using nuclear magnetic resonance (NMR) spectroscopy. Both one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy was used for the assignment of metabolites in urine from unexposed fish. Because fathead minnow urine is dilute, we lyophilized these samples prior to analysis. Furthermore, 1D 1 H NMR spectra of unlyophilized urine from unexposed male fathead minnow and Sprague-Dawley rat were acquired to qualitatively compare rat and fish metabolite profiles and to provide an estimate of the total urinary metabolite pool concentration difference. As a small proof-of-concept study, lyophilized urine samples from male fathead minnows exposed to three different concentrations of the antiandrogen vinclozolin were analyzed by 1D 1 H NMR to assess exposure-induced changes. Through a combination of principal components analysis (PCA) and measurements of 1 H NMR peak intensities, several metabolites were identified as changing with statistical significance in response to exposure. Among those changes occurring in response to exposure to the highest concentration (450 μg/L) of vinclozolin were large increases in taurine, lactate, acetate, and formate. These increases coincided with a marked decrease in hippurate, a combination potentially indicative of hepatotoxicity. The results of these investigations clearly demonstrate the potential utility of an NMR-based approach for assessing chemical exposures in male fathead minnow, using urine collected from individual fish

Isolation and identification of probiotic lactic acid bacteria from donkey,s milk

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Mohamad javad Akrami

2016-02-01

Full Text Available Background : The utilization of donkey’s milk is increasing with regard to nutritional values and non-allergenic proteins. Donkey’s milk microbiota, especially lactic acid bacteria (LAB has not yet been fully identified. This study was conducted to identify and isolate LAB with probiotic properties. Materials and Methods: Specific culture-dependent techniques and standard microbiology methods were used to identify LAB. 250 isolates were randomly picked from different donkey’s milk samples different farms in Alashtar, north of Lorestan province, Iran. Gram-staining, catalase reaction, motility test, growth at different temperatures, pH 9.6 and in presence of 6.5% NaCl as well as the ability to ferment different sugars, sodium hippurate hydrolysis and light microscope analysis were investigated. Results: Out of 250 isolates, 20 isolates were gram-positive, catalase-negative and cocci form. Enterococcus and Streptoccus genera were dominant LAB in donkey’s milk. Entreococcus faecalis (55% and Streptococcus devriesei (45% were among the predominant species. The results of this experiment, for the first time, reported the occurrence of Streptococcus devriesei in donkey’s milk in Iran. Conclusion: Despite high lysozyme concentration, donkey’s milk rich in probiotic LAB can be used to feed infants with allergy to cow’s milk proteins. Both Entreococcus and Streptococcus bacteria produce different types of bacteriocins which are effective against a wide range of different type of infections. Occurrence of Streptococcus devriesei in donkey,s milk may provide new research field in Iran.

Appraisal of the renal function in health donors of the Specialities Hospital Centro Medico La Raza, IMSS; Valoracion de la funcion renal en donadores sanos del Hospital de Especialidades Centro Medico La Raza, IMSS

Energy Technology Data Exchange (ETDEWEB)

Llanos O, S.V

2004-07-01

The techniques of Nuclear Medicine (MN) represent the most reliable and sure forms in measurement of the glomeruli filtrate (FG) and of the effective renal plasmatic flow (FPRE), by means of a simple, practical, innocuous and economic method that doesn't require urine gathering, available in the services of (MN). The renal gamma gram is at the moment the election procedure in the diagnosis and evaluation of diverse nephro urological pathologies since it provides objective information of the renal function as well as of the characteristics of the drainage of the urinal tract. They provide to the clinical doctor a real measurement of the state of the purifying renal function. their determinations are not affected by the habitual protein ingesta, they can be made with any level of seric creatinine, the exercise, size, sex. Their methodology uses the unique injection technique for each one, in which the renal purification is determined by means of Gary Gates method and the tubular secretion by based on the method of Schlegel. These techniques show a very high correlation coefficient with those standard of gold and they lack the inherent inconveniences to the technique of urine gathering. The used radiopharmaceuticals are diethylen triamine penta acetic-Tc {sup 99m} acid and Orto iodine hippurate- I{sup 131} the only requirement for the realization of the study is an appropriate hydration (10-15 ml/Kg is calculated.) (Author)

Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal Hemodynamics in Severely Obese Individuals

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Edoardo Vitolo

2016-10-01

Full Text Available Objective: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR is unusual, and how estimation formulae (EstForm perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm. Methods: We measured GFR (mGFR by iohexol plasma clearance, renal plasma flow (RPF by 123I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects. Results: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland-Altman analysis. mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R2 = 0.67, accounting for 15% and 21% of mGFR variance, respectively. Conclusions: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR.

Spontaneous variability of pre-dialysis concentrations of uremic toxins over time in stable hemodialysis patients.

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Sunny Eloot

Full Text Available Numerous outcome studies and interventional trials in hemodialysis (HD patients are based on uremic toxin concentrations determined at one single or a limited number of time points. The reliability of these studies however entirely depends on how representative these cross-sectional concentrations are. We therefore investigated the variability of predialysis concentrations of uremic toxins over time.Prospectively collected predialysis serum samples of the midweek session of week 0, 1, 2, 3, 4, 8, 12, and 16 were analyzed for a panel of uremic toxins in stable chronic HD patients (N = 18 while maintaining dialyzer type and dialysis mode during the study period.Concentrations of the analyzed uremic toxins varied substantially between individuals, but also within stable HD patients (intra-patient variability. For urea, creatinine, beta-2-microglobulin, and some protein-bound uremic toxins, Intra-class Correlation Coefficient (ICC was higher than 0.7. However, for phosphorus, uric acid, symmetric and asymmetric dimethylarginine, and the protein-bound toxins hippuric acid and indoxyl sulfate, ICC values were below 0.7, implying a concentration variability within the individual patient even exceeding 65% of the observed inter-patient variability.Intra-patient variability may affect the interpretation of the association between a single concentration of certain uremic toxins and outcomes. When performing future outcome and interventional studies with uremic toxins other than described here, one should quantify their intra-patient variability and take into account that for solutes with a large intra-patient variability associations could be missed.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats

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Muhammad Tayyab Akhtar

2016-08-01

Full Text Available Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM. Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM. Proton Nuclear Magnetic Resonance (1H-NMR spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese–diabetic (obdb rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

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Berg, Ulla B; Németh, Antal

2018-04-01

On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

Feline urine metabolomic signature: characterization of low-molecular-weight substances in urine from domestic cats.

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Rivera-Vélez, Sol-Maiam; Villarino, Nicolas F

2018-02-01

Objectives This aim of this study was to characterize the composition and content of the feline urine metabolome. Methods Eight healthy domestic cats were acclimated at least 10 days before starting the study. Urine samples (~2 ml) were collected by ultrasound-guided cystocentesis. Samples were centrifuged at 1000 × g for 8 mins, and the supernatant was analyzed by gas chromatography/time-of-flight mass spectrometery. The urine metabolome was characterized using an untargeted metabolomics approach. Results Three hundred and eighteen metabolites were detected in the urine of the eight cats. These molecules are key components of at least 100 metabolic pathways. Feline urine appears to be dominated by carbohydrates, carbohydrate conjugates, organic acid and derivatives, and amino acids and analogs. The five most abundant molecules were phenaceturic acid, hippuric acid, pseudouridine phosphate and 3-(4-hydroxyphenyl) propionic acid. Conclusions and relevance This study is the first to characterize the feline urine metabolome. The results of this study revealed the presence of multiple low-molecular-weight substances that were not known to be present in feline urine. As expected, the origin of the metabolites detected in urine was diverse, including endogenous compounds and molecules biosynthesized by microbes. Also, the diet seemed to have had a relevant role on the urine metabolome. Further exploration of the urine metabolic phenotype will open a window for discovering unknown, or poorly understood, metabolic pathways. In turn, this will advance our understanding of feline biology and lead to new insights in feline physiology, nutrition and medicine.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

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Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

2010-03-01

As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

Plasma metabonomics study on toxicity biomarker in rats treated with Euphorbia fischeriana based on LC-MS.

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Wang, Yingfeng; Man, Hongxue; Gao, Jian; Liu, Xinfeng; Ren, Xiaolei; Chen, Jianxin; Zhang, Jiayu; Gao, Kuo; Li, Zhongfeng; Zhao, Baosheng

2016-09-01

Lang-du (LD) has been traditionally used to treat human diseases in China. Plasma metabolic profiling was applied in this study based on LC-MS to elucidate the toxicity in rats induced by injected ethanol extract of LD. LD injection was given by intraperitoneal injection at doses of 0.1, 0.05, 0.025 and 0 g kg(-1) body weight per day to rats. The blood biochemical levels of alanine aminotransferase, direct bilirubin, creatinine, serum β2-microglobulin and low-density lipoprotein increased in LD-injected rats, and the levels of total protein and albumin decreased in these groups. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structures discriminate analysis (OPLS-DA). The metabolic characters in rats injected with LD were perturbed in a dose-dependent manner. By OPLS-DA, 18 metabolites were served as the potential toxicity biomarkers. Moreover, LD treatment resulted in an increase in the p-cresol, p-cresol sulfate, lysophosphatidylethanolamine (LPE) (18:0), LPE (16:0), lysophosphatidylcholine (16:0) and 12-HETE concentrations, and a decrease in hippuric acid, cholic acid and N-acetyl-l-phenylalanine. These results suggested that chronic exposure to LD could cause a disturbance in lipids metabolism and amino acids metabolism, etc. Therefore, an analysis of the metabolic profiles can contribute to a better understanding of the adverse effects of LD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Combination of ¹H NMR- and GC-MS-based metabonomics to study on the toxicity of Coptidis Rhizome in rats.

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Yuting Zhou

Full Text Available BACKGROUND: Coptidis Rhizome (CR, widely applied to treat with heat and toxicity, is one of the most commonly used traditional Chinese medicine (TCM, however, an extensive dosage can induce toxicity. Diarrhea is one of the most frequent side effects of CR treatment. METHODOLOGY/PRINCIPAL FINDINGS: In this study, metabonomics was combined with the multivariate statistical analysis to discover the endogenous metabolites which related to the diarrheal induced by CR. The male Sprague-Dawley rats were dosed with 4.95 g CR/kg weight. Urine samples were collected at day -1 (before treatment, and days 14 and 21 for NMR analysis. Serum and tissues were collected at day 14 for GC-MS analysis and histopathological examination, respectively. The urine and serum metabolic profiles provided clearer distinction between CR-treated group and control group, which was confirmed by body weight change and diarrhea. Through multivariate statistical analysis, 12 marker metabolites from ¹H NMR and 8 ones from GC-MS have been found. Among those metabolites, hippurate, acetate, alanine, glycine and glutamate are likely to break the balance of gut microbiota, whereas, lactate and 2-ketoisovalerate showed association with energy metabolism. Meanwhile, we observed that the CR-induced toxicity will recover when the treatment was stopped. CONCLUSIONS/SIGNIFICANCE: These results suggest that the main reason for the CR-associated diarrhea might be disturbance in the normal gut microbiota. This metabonomics approach may provide an effective way to study the alteration of gut microbiota, which is expected to find broader application in other drug-induced gastrointestinal reaction assessment.

NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure to PCBs and TCDD in rats

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Lu Chunfeng; Wang Yimei; Sheng Zhiguo; Liu Gang; Fu Ze; Zhao Jing; Zhao Jun; Yan Xianzhong; Zhu Benzhan; Peng Shuangqing

2010-01-01

A metabonomic approach using 1 H NMR spectroscopy was adopted to investigate the metabonomic pattern of rat urine after oral administration of environmental endocrine disruptors (EDs) polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) alone or in combination and to explore the possible hepatotoxic mechanisms of combined exposure to PCBs and TCDD. 1 H NMR spectra of urines collected 24 h before and after exposure were analyzed via pattern recognition by using principal component analysis (PCA). Serum biochemistry and liver histopathology indicated significant hepatotoxicity in the rats of the combined group. The PCA scores plots of urinary 1 H NMR data showed that all the treatment groups could be easily distinguished from the control group, so could the PCBs or TCDD group and the combined group. The loadings plots of the PCA revealed remarkable increases in the levels of lactate, glucose, taurine, creatine, and 2-hydroxy-isovaleric acid and reductions in the levels of 2-oxoglutarate, citrate, succinate, hippurate, and trimethylamine-N-oxide in rat urine after exposure. These changes were more striking in the combined group. The changed metabolites may be considered possible biomarker for the hepatotoxicity. The present study demonstrates that combined exposure to PCBs and TCDD induced significant hepatotoxicity in rats, and mitochondrial dysfunction and fatty acid metabolism perturbations might contribute to the hepatotoxicity. There was good conformity between changes in the urine metabonomic pattern and those in serum biochemistry and liver histopathology. These results showed that the NMR-based metabonomic approach may provide a promising technique for the evaluation of the combined toxicity of EDs.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

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Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan; Yan Guangyan; Cen Xiaobo; Deng Pengchi; Peng Feng; Xue Aiqin; Wang Yanli

2010-01-01

As titanium dioxide nanoparticles (TiO 2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO 2 NPs (dosed at 0.16, 0.4 and 1 g kg -1 , respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1 H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO 2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO 2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO 2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO 2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

Stress transgenerationally programs metabolic pathways linked to altered mental health.

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Kiss, Douglas; Ambeskovic, Mirela; Montina, Tony; Metz, Gerlinde A S

2016-12-01

Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress lineage (the great-great-grandmother and each subsequent generation experienced stress during pregnancy) and a transgenerational stress lineage (only the great-great-grandmother was stressed during pregnancy). Urine samples were collected from adult male F4 offspring and analyzed using 1 H NMR spectroscopy. The results of variable importance analysis based on random variable combination were used for unsupervised multivariate principal component analysis and hierarchical clustering analysis, as well as metabolite set enrichment analysis (MSEA) and pathway analysis. We identified distinct metabolic profiles associated with the multigenerational and transgenerational stress phenotype, with consistent upregulation of hippurate and downregulation of tyrosine, threonine, and histamine. MSEA and pathway analysis showed that these metabolites are involved in catecholamine biosynthesis, immune responses, and microbial host interactions. The identification of metabolic signatures linked to ancestral programming assists in the discovery of gene targets for future studies of epigenetic regulation in pathogenic processes. Ultimately, this research can lead to biomarker discovery for better prediction and prevention of mental health disorders.

Application of ultraperformance liquid chromatography/mass spectrometry-based metabonomic techniques to analyze the joint toxic action of long-term low-level exposure to a mixture of organophosphate pesticides on rat urine profile.

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Du, Longfei; Wang, Hong; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhang, Yuqiu; Zhao, Xiujuan; Sun, Changhao

2013-07-01

In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL). Results show that a single pesticide elicits no toxic response. This study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology. Pesticides were administered daily to rats through drinking water for 24 weeks. The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide. The metabonomic profiles of rats urine were analyzed by ultraperformance liquid chromatography/mass spectrometry. The 16 metabolites statistically significantly changed in all treated groups compared with the control group. Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides. Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine, and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid, and citric acid. The results indicated that a mixture of OP pesticides induced DNA damage and oxidative stress, disturbed the metabolism of lipids, and interfered with the tricarboxylic acid cycle. Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake but also the joint toxic action.

In vitro metabolism of [14C]-toluene by human and rat liver microsomes and liver slices

International Nuclear Information System (INIS)

Chapman, D.E.; Moore, T.J.; Michener, S.R.; Powis, G.

1990-01-01

Toluene metabolites produced by liver microsomes from six human donors included benzylalcohol (Balc), benzaldehyde (Bald) and benzoic acid (Bacid). Microsomes from only one human donor metabolized toluene to p-cresol and o-cresol. Human liver microsomes also metabolized Balc to Bald. Balc metabolism required NADPH, was inhibited by carbon monoxide, and was decreased at a buffer pH of 10. Balc metabolism was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P450 is responsible for the in vitro metabolism of Balc by human liver microsomes. Toluene metabolites formed by human liver slices and released into the incubation media included hippuric acid, and Bacid. Cresols or cresol-conjugates were not detected in liver slice incubation media from any human donor. Toluene metabolism by human liver was compared to metabolism by comparable liver preparations from male Fischer F344 rats. Rates of toluene metabolism by human liver microsomes and liver slices were 9-fold and 1.3-fold greater than for rat liver, respectively. Covalent binding of toluene to human liver microsomes and liver slices was 21-fold and 4-fold greater than for comparable rat liver preparations. Covalent binding of toluene to human microsomes required NADPH, was significantly decreased by coincubation with 4 mM cysteine or 4 mM glutathione, and radioactivity associated with microsomes was decreased by subsequent digestion of microsomes with protease. These results suggest that toluene metabolism and covalent binding of toluene are underestimated if the male Fischer 344 rat is used as a model for human toluene metabolism

Metabolic interaction between n-hexane and toluene in vivo and in vitro

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Perbellini, L.; Brugnone, F.; Leone, R.; Fracasso, M.E.; Venturini, M.S.

1982-01-01

Metabolic interference between n-hexane and toluene was studied both in vivo and in vitro. In in vivo experiments the urinary excretion of n-hexane and toluene metabolites was tested in rats treated with the two solvents separately or in combination. The same experimental program was repeated in rats pretreated with phenobarbital (PB). The urinary excretion of n-hexane metabolites in rats treated with the two solvents showed a significantly decreased excretion of all n-hexane metabolites in comparison with those treated with n-hexane alone. In rats pretreated with PB the excretion of n-hexane metabolites was significantly higher compared with that of unpretreated rats; the combined administration of the two solvents showed in this case, too, that n-hexane metabolite excretion was less than that found in rats treated with n-hexane alone. The biotransformation of toluene to o-cresol and hippuric acid studied in the urine of rats treated with or without n-hexane and pretreated or not with PB did not show any difference. The in vitro metabolic interference was studied by measuring the disappearance of solvents from rat's incubated liver microsomes. The inhibition constant of toluene on n-hexane biotransformation was 7.5 ..mu..M and that of n-hexane on toluene was 30 ..mu..M. The data show that a mutual non-competitive interference exists in vitro between n-hexane and toluene. The interference of toluene on n-hexane biotransformation was detectable also in vivo experiments, while n-hexane did not modify the biotransformation of toluene.

Urinary metabolomic profiling in rats exposed to dietary di(2-ethylhexyl) phthalate (DEHP) using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS).

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Dong, Xinwen; Zhang, Yunbo; Dong, Jin; Zhao, Yue; Guo, Jipeng; Wang, Zhanju; Liu, Mingqi; Na, Xiaolin; Wang, Cheng

2017-07-01

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental chemical with widespread nonoccupational human exposure through multiple ways. Although considerable efforts have been invested to investigate mechanisms of DEHP toxicity, the key metabolic biomarkers of DEHP toxicity remain to be identified. The aim of this study was to assess the urinary metabonomics of dietary DEHP in rats using the technique of ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). Fourteen female Wistar rats were divided into two groups and given increasing dietary doses of DEHP for 30 consecutive days. The urinary metabolite profile was studied using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) enabled clusters to be clearly separated. Eleven principal urinary metabolites were identified as contributing to the clusters. The clusters in the positive electrospray ionization (ESI) mode were xanthurenic acid, kynurenic acid, nonate, N6-methyladenosine, and L-isoleucyl-L-proline. The clusters in the negative ESI mode were hippuric acid, tetrahydrocortisol, citric acid, phenylpropionylglycine, cPA(18:2(9Z, 12Z)/0:0), and LysoPC(14:1(9Z)). The urinary metabonomic changes indicated that exposure to dietary DEHP can affect energy-related metabolism, liver and renal function, fatty acid metabolism, and cause DNA damage in rats. The findings of this study on the urinary metabolites and metabolic pathways of DEHP may form the basis for future studies on the mechanisms of toxicity of this commonly found environmental chemical.

Toxicological effects of cinnabar in rats by NMR-based metabolic profiling of urine and serum

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Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing; Pei Fengkui; Li Weisheng; Wu Yijie

2008-01-01

Cinnabar, an important traditional Chinese mineral medicine, has been widely used as a Chinese patent medicine ingredient for sedative therapy. However, the pharmaceutical and toxicological effects of cinnabar, especially in the whole organism, were subjected to few investigations. In this study, an NMR-based metabolomics approach has been applied to investigate the toxicological effects of cinnabar after intragastrical administration (dosed at 0.5, 2 and 5 g/kg body weight) on male Wistar rats. Liver and kidney histopathology examinations and serum clinical chemistry analyses were also performed. The 1 H NMR spectra were analyzed using multivariate pattern recognition techniques to show the time- and dose-dependent biochemical variations induced by cinnabar. The metabolic signature of urinalysis from cinnabar-treated animals exhibited an increase in the levels of creatinine, acetate, acetoacetate, taurine, hippurate and phenylacetylglycine, together with a decrease in the levels of trimethyl-N-oxide, dimethylglycine and Kreb's cycle intermediates (citrate, 2-oxoglutarate and succinate). The metabolomics analyses of serum showed elevated concentrations of ketone bodies (3-D-hydroxybutyrate and acetoacetate), branched-chain amino acids (valine, leucine and isoleucine), choline and creatine as well as decreased glucose, lipids and lipoproteins from cinnabar-treated animals. These findings indicated cinnabar induced disturbance in energy metabolism, amino acid metabolism and gut microflora environment as well as slight injury in liver and kidney, which might indirectly result from cinnabar induced oxidative stress. This work illustrated the high reliability of NMR-based metabolomic approach on the study of the biochemical effects induced by traditional Chinese medicine

Metabolic profiling studies on the toxicological effects of realgar in rats by 1H NMR spectroscopy

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Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing; Pei Fengkui; Li Weisheng; Wu Yijie

2009-01-01

The toxicological effects of realgar after intragastrical administration (1 g/kg body weight) were investigated over a 21 day period in male Wistar rats using metabonomic analysis of 1 H NMR spectra of urine, serum and liver tissue aqueous extracts. Liver and kidney histopathology examination and serum clinical chemistry analyses were also performed. 1 H NMR spectra and pattern recognition analyses from realgar treated animals showed increased excretion of urinary Kreb's cycle intermediates, increased levels of ketone bodies in urine and serum, and decreased levels of hepatic glucose and glycogen, as well as hypoglycemia and hyperlipoidemia, suggesting the perturbation of energy metabolism. Elevated levels of choline containing metabolites and betaine in serum and liver tissue aqueous extracts and increased serum creatine indicated altered transmethylation. Decreased urinary levels of trimethylamine-N-oxide, phenylacetylglycine and hippurate suggested the effects on the gut microflora environment by realgar. Signs of impairment of amino acid metabolism were supported by increased hepatic glutamate levels, increased methionine and decreased alanine levels in serum, and hypertaurinuria. The observed increase in glutathione in liver tissue aqueous extracts could be a biomarker of realgar induced oxidative injury. Serum clinical chemistry analyses showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. The time-dependent biochemical variations induced by realgar were achieved using pattern recognition methods. This work illustrated the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by traditional Chinese medicine

The rebirth of interest in renal tubular function.

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Lowenstein, Jerome; Grantham, Jared J

2016-06-01

The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. Copyright © 2016 the American Physiological Society.

NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

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Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

2010-03-26

As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

A urinary metabonomics analysis of long-term effect of acetochlor exposure on rats by ultra-performance liquid chromatography/mass spectrometry.

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Li, Longxue; Wang, Maoqing; Chen, Shuhong; Zhao, Wei; Zhao, Yue; Wang, Xu; Zhang, Yang

2016-03-01

The study was to assess the long-term toxic effects of acetochlor on rats. Two different doses (42.96 and 107.4 mg/kg body weight/day) of acetochlor were administered to Wistar rats through their food for over 24 weeks. Rat urine samples were collected at two time-points for the measurements of the metabonomics profiles with ultra-performance liquid chromatography-mass spectrometry (UPLC-MSMS). The results of clinical chemistry and histopathology suggested that long-term use of acetochlor in rats caused liver and kidney damage, and dysfunction of antioxidant system. The urinary metabonomics analysis indicated that the high and low-dose exposure of acetochlor could cause alterations of these metabonomics in urine in the rat. Significant changes of the levels of hippuric acid (0.403-fold decrease), citric acid (0.430-fold decrease), pantothenic acid (0.486-fold decrease), uracil (0.419-fold decrease), β-Alanine (0.325-fold decrease), nonanedioic acid (0.445-fold decrease), L-tyrosine (0.410-fold decrease), D-glucuronic acid (8.389-fold increase) and 2-ethyl-6-methyl-N-methyl-2-chloro-acetanilide in urine were observed. In addition, it may interfere with the fatty acid synthesis, the pyrimidine degradation and pantothenate biosynthesis. The level of 2-ethyl-6-methyl-N-methyl-2-chloro-acetanilide is detected in all treated groups which is not found in the control groups, indicating which can be used as an early, sensitive marker of acetochlor exposure in rat. This study illustrates the important utility of metabonomics approaches to understand the toxicity of long-term exposure of acetochlor. Copyright © 2015. Published by Elsevier Inc.

Triamide mercaptide (N/sub 3/S) ligands for Tc-99m as potential Tc-99m renal function agents

International Nuclear Information System (INIS)

Fritzberg, A.R.; Kasina, S.; Johnson, D.L.; Eshima, D.

1985-01-01

A number of diamide dimercaptide (N/sub 2/S/sub 2/) complexes of Tc-99m have shown potential as renal tubular function radiopharmaceuticals that could replace radioiodinated hippurate (OIH). Evaluation of such ligands suggested that maximum efficiency for tubular secretion and specificity resulted from addition of a carboxylate group. However, such derivatives resulted in chelate ring stereoisomers that were differently transported by the renal tubular system. The problem of stereoisomers was obviated by replacing one sulfur with an effectively planar amido nitrogen. Groups on the nitrogen then result in diastereomers only when an additional asymetric center is present. A series of triamide mercaptide compounds have been synthesized to evaluate this class as ligands for Tc-99m. One of the simplest of the series, mercaptoacetylglycylglycylglycine (MAG/sub 3/), formed a single Tc-99m product in high yield as determined by HPLC. Preliminary results with pmr and ms of the Tc-99 complex indicate a structure consistent with a 1:1 metal to ligand ratio and monooxo technetium group. Biological evaluation of Tc-99m MAG/sub 3/ showed high renal specificity and rate of excretion exceeding OIH in several species including humans. Members of the N/sub 3/S series studied include mercaptoacetylglycylglycyl-amino acids. In some cases with second asymmetric centers, two components were seen on HPLC. In mice several dianionic Tc-99m complexes were excreted faster than OIH, Tc-99m MAG/sub 2/-ala, -asn, and -gln. Trianionic Tc-99m MAG/sub 2/-asp and -glu were excreted more slowly, and Tc-99m MAG/sub 2/-phe showed hepatobiliary excretion. Triamide mercaptides represent a new ligand class for Tc-99m

Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: patient perspectives.

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Peña-Quintana, Luis; Llarena, Marta; Reyes-Suárez, Desiderio; Aldámiz-Echevarria, Luis

2017-01-01

Urea-cycle disorders are a group of rare hereditary metabolic diseases characterized by deficiencies of one of the enzymes and transporters involved in the urea cycle, which is necessary for the removal of nitrogen produced from protein breakdown. These hereditary metabolic diseases are characterized by hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. Sodium benzoate combines with glycine and phenylacetate/phenylbutyrate with glutamine, forming, respectively, hippuric acid and phenylacetylglutamine, which are eliminated in the urine. Among the ammonia-scavenging drugs, sodium phenylbutyrate is a well-known long-term treatment of urea-cycle disorders. It has been used since 1987 as an investigational new drug, and was approved for marketing in the US in 1996 and the EU in 1999. However, sodium phenylbutyrate has an aversive odor and taste, which may compromise patients' compliance, and many patients have reported difficulty in taking this drug. Sodium phenylbutyrate granules are a new tasteless and odor-free formulation of sodium phenylbutyrate, which is indicated in the treatment of urea-cycle disorders. This recently developed taste-masked formulation of sodium phenylbutyrate granules was designed to overcome the considerable issues that taste has on adherence to therapy. Several studies have reported the clinical experience of patients with urea-cycle disorders treated with this new tasteless formulation of sodium phenylbutyrate. Analysis of the data indicated that this taste-masked formulation of sodium phenylbutyrate granules improved quality of life for urea-cycle disorder patients. Furthermore, a postmarketing report on the use of the product has confirmed the previous observations of improved compliance, efficacy, and safety with this taste-masked formulation of sodium phenylbutyrate.

Combined untargeted and targeted fingerprinting by comprehensive two-dimensional gas chromatography: revealing fructose-induced changes in mice urinary metabolic signatures.

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Bressanello, Davide; Liberto, Erica; Collino, Massimo; Chiazza, Fausto; Mastrocola, Raffaella; Reichenbach, Stephen E; Bicchi, Carlo; Cordero, Chiara

2018-04-01

This study exploits the information potential of comprehensive two-dimensional gas chromatography configured with a parallel dual secondary column-dual detection by mass spectrometry and flame ionization (GC×2GC-MS/FID) to study changes in urinary metabolic signatures of mice subjected to high-fructose diets. Samples are taken from mice fed with normal or fructose-enriched diets provided either in aqueous solution or in solid form and analyzed at three stages of the dietary intervention (1, 6, and 12 weeks). Automated Untargeted and Targeted fingerprinting for 2D data elaboration is adopted for the most inclusive data mining of GC×GC patterns. The UT fingerprinting strategy performs a fully automated peak-region features fingerprinting and combines results from pre-targeted compounds and unknowns across the sample-set. The most informative metabolites, with statistically relevant differences between sample groups, are obtained by unsupervised multivariate analysis (MVA) and cross-validated by multi-factor analysis (MFA) with external standard quantitation by GC-MS. Results indicate coherent clustering of mice urine signatures according to dietary manipulation. Notably, the metabolite fingerprints of mice fed with liquid fructose exhibited greater derangement in fructose, glucose, citric, pyruvic, malic, malonic, gluconic, cis-aconitic, succinic and 2-keto glutaric acids, glycine acyl derivatives (N-carboxy glycine, N-butyrylglycine, N-isovaleroylglycine, N-phenylacetylglycine), and hippuric acid. Untargeted fingerprinting indicates some analytes which were not a priori pre-targeted which provide additional insights: N-acetyl glucosamine, N-acetyl glutamine, malonyl glycine, methyl malonyl glycine, and glutaric acid. Visual features fingerprinting is used to track individual variations during experiments, thereby extending the panorama of possible data elaboration tools. Graphical abstract ᅟ.

Effect of Ipomoea aquatica ethanolic extract in streptozotocin (STZ) induced diabetic rats via1H NMR-based metabolomics approach.

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Abu Bakar Sajak, Azliana; Mediani, Ahmed; Maulidiani; Mohd Dom, Nur Sumirah; Machap, Chandradevan; Hamid, Muhajir; Ismail, Amin; Khatib, Alfi; Abas, Faridah

2017-12-01

Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown. This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract. By using a combination of 1 H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified. The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified. I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism. Copyright © 2017 Elsevier GmbH. All rights reserved.

Impact of bioaccessibility and bioavailability of phenolic compounds in biological systems upon the antioxidant activity of the ethanolic extract of Triplaris gardneriana seeds.

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Neto, José Joaquim Lopes; de Almeida, Thiago Silva; de Medeiros, Jackeline Lima; Vieira, Leonardo Rogério; Moreira, Thaís Borges; Maia, Ana Isabel Vitorino; Ribeiro, Paulo Riceli Vasconcelos; de Brito, Edy Sousa; Farias, Davi Felipe; Carvalho, Ana Fontenele Urano

2017-04-01

The most studied bioactive potential of phenolic compounds corresponds to antioxidant activity, which in turn, is associated with a reduction in the incidence of various human diseases. However, the total quantity of these bioactive substances in foods and medicinal preparations does not reflect the amount absorbed and metabolized by the body. The present study aimed to investigate the bioaccessibility of Triplaris gardneriana seeds ethanolic extract (EETg) by determination of phenolic composition and antioxidant activities before and after in vitro digestion as well as to estimate its bioavailability by chemical analysis of plasma and urine in animal models after oral administration. The bioaccessibility indexes of phenolic compounds in EETg were 48.65 and 69.28% in the presence and absence of enzymes, respectively. Among the identified phenolics classes, flavonoids, represented by galloylated procyanidins type B, proved to be more bioaccessible, 81.48 and 96.29% in the post-intestinal phase with and without enzymes, respectively. The oral administration in Wistar rats resulted in a significant decrease in plasma of the total antioxidant capacity, TAC, by FRAP assay 4h after beginning the experiment. For urine samples, an increase in TAC by DPPH and FRAP was observed from 1 and 4h after administration, respectively. UPLC-QTOF analysis of urine detected 2 metabolites originated from the degradation of phenolic compounds, i.e. hippuric acid and phenylacetil glycine. These results suggest that phenolic compounds in T. gardneriana are unstable under gastrointestinal conditions, being flavonoids the components with higher bioaccessibility; besides that, they showed limited bioavailability due to their rapid biotransformation and urinary elimination. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Concomitant ingestion of lactic acid bacteria and black tea synergistically enhances flavonoid bioavailability and attenuates d-galactose-induced oxidative stress in mice via modulating glutathione antioxidant system.

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Zhao, Danyue; Shah, Nagendra P

2016-12-01

Black tea (BT) has been positively linked to improved redox status, while its efficacy is limited due to the low bioavailability of BT flavonoids. In addition to the direct antioxidant activity, flavonoids regulate redox balance via inducing endogenous antioxidants, particularly glutathione (GSH) and GSH-dependent antioxidant enzymes. This work first examined the effect of lactic acid bacteria (LAB) and BT alone or in combination on flavonoid bioavailability and metabolism; next, the effect of LAB-fermented BT diet in attenuating oxidative stress in mice and the underlying mechanisms were studied. Phenolic profiles of plasma, urine and feces from healthy mice consuming plain yogurt, BT milk (BTM) or BT yogurt (BTY) were acquired using LC-MS/MS. Plasma antioxidant capacity, lipid peroxidation level, content of nonprotein thiols and expression of GSH-related antioxidant enzymes and Nrf2 were examined in d-galactose-treated mice. Total flavonoid content in plasma following a single dose of BTY attained 0.657 μmol/l, increased by 50% compared with the BTM group. Increased excretion of phenolic metabolite and hippuric acid in urine and feces indicated enhanced metabolism of flavonoids in BTY-fed mice. In the second study, 8-week concomitant LAB-BT treatment of oxidatively stressed mice effectively restored plasma antioxidant capacity and GSH levels, and mitigated lipid peroxidation, which were associated with significant induction of GSH-dependent antioxidant enzymes and nuclear accumulation of Nrf2. Our results demonstrated the effect of LAB fermentation in enhancing BT flavonoid bioavailability in vivo. The synergistic antioxidant efficacy of LAB-BT diet implied its therapeutic potential in enhancing antioxidant defenses and protecting organisms from oxidative damage. Copyright © 2016. Published by Elsevier Inc.

Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

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Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

2017-04-01

Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

Prevention of Renal Injury After Induction of Ozone Tolerance in Rats Submitted to Warm Ischaemia

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E. Barber

1999-01-01

Full Text Available On the basis that ozone (O3 can upregulate cellular antioxidant enzymes, a morphological, biochemical and functional renal study was performed in rats undergoing a prolonged treatment with O3 before renal ischaemia. Rats were divided into four groups: (1 control, a medial abdominal incision was performed to expose the kidneys; (2 ischaemia, in animals undergoing a bilateral renal ischaemia (30 min, with subsequent reperfusion (3 h; (3 O3 + ischaemia, as group 2, but with previous treatment with O3 (0.5 mg/kg per day given in 2.5 ml O2 via rectal administration for 15 treatments; (4 O2 + ischaemia, as group 3, but using oxygen (O2 alone. Biochemical parameters as fructosamine level, phospholipase A, and superoxide dismutases (SOD activities, as well as renal plasma flow (RPF and glomerular filtration rate (GFR, were measured by means of plasma clearance of p-amino-hippurate and inulin, respectively. In comparison with groups 1 and 3, the RPF and GFR were significantly decreased in groups 2 and 4. Interestingly, renal homogenates of the latter groups yielded significantly higher values of phospholipase A activity and fructosamine level in comparison with either the control (1 and the O3 (3 treated groups. Moreover renal SOD activity showed a significant increase in group 3 without significant differences among groups 1, 2 and 4. Morphological alterations of the kidney were present in 100%, 88% and 30% of the animals in groups 2, 4 and 3, respectively. It is proposed that the O3 protective effect can be ascribed to the substantial possibility of upregulating the antioxidant defence system capable of counteracting the damaging effect of ischaemia. These findings suggest that, whenever possible, ozone preconditioning may represent a prophylactic approach for minimizing renal damage before transplantation.

Short-term inhalation toxicity of methanol, gasoline, and methanol/gasoline in the rat.

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Poon, R; Chu, I; Bjarnason, S; Vincent, R; Potvin, M; Miller, R B; Valli, V E

1995-01-01

Four- to five-week-old male and female Sprague Dawley rats were exposed to vapors of methanol (2500 ppm), gasoline (3200 ppm), and methanol/gasoline (2500/3200 ppm, 570/3200 ppm) six hours per day, five days per week for four weeks. Control animals were exposed to filtered room air only. Depression in body weight gain and reduced food consumption were observed in male rats, and increased relative liver weight was detected in rats of both sexes exposed to gasoline or methanol/gasoline mixtures. Rats of both sexes exposed to methanol/gasoline mixtures had increased relative kidney weight and females exposed to gasoline and methanol/gasoline mixtures had increased kidney weight. Decreased serum glucose and cholesterol were detected in male rats exposed to gasoline and methanol/gasoline mixtures. Decreased hemoglobin was observed in females inhaling vapors of gasoline and methanol/gasoline at 570/3200 ppm. Urine from rats inhaling gasoline or methanol/gasoline mixtures had up to a fourfold increase in hippuric acid, a biomarker of exposure to the toluene constituent of gasoline, and up to a sixfold elevation in ascorbic acid, a noninvasive biomarker of hepatic response. Hepatic mixed-function oxidase (aniline hydroxylase, aminopyrine N-demethylase and ethoxyresorufin O-deethylase) activities and UDP-glucuronosyltransferase activity were elevated in rats exposed to gasoline and methanol/gasoline mixtures. Histopathological changes were confined to very mild changes in the nasal passages and in the uterus, where decreased incidence or absence of mucosal and myometrial eosinophilia was observed in females inhaling gasoline and methanol/gasoline at 570/3200 ppm. It was concluded that gasoline was largely responsible for the adverse effects, the most significant of which included depression in weight gain in the males, increased liver weight and hepatic microsomal enzyme activities in both sexes, and suppression of uterine eosinophilia. No apparent interactive effects

Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease.

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Barbara, Giovanni; Scaioli, Eleonora; Barbaro, Maria Raffaella; Biagi, Elena; Laghi, Luca; Cremon, Cesare; Marasco, Giovanni; Colecchia, Antonio; Picone, Gianfranco; Salfi, Nunzio; Capozzi, Francesco; Brigidi, Patrizia; Festi, Davide

2017-07-01

The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by 1 H nuclear magnetic resonance. Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia . Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy. Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease. Published by the BMJ Publishing Group Limited

Exercise induced renal dysfunction demonstrated both in hypertensives and normotensive controls studies by Tc-99m-DTPA

International Nuclear Information System (INIS)

Mizuiri, S.; Hayashi, I.; Ohara, T.; Hirata, K.; Sasaki, Y.

1985-01-01

It was previously reported that the hippurate transport disturbance after exercise is a specific phenomenon to patients with hypertension. The authors' study with Tc-99m-DTPA revealed exercise induced renal dysfunction not only in hypertensives (H) but also in normotensive controls (N). The details of the investigation is presented. Tc-99m-DTPA was intravenously injected at rest and during bicycle ergometric stress to 14 H and 14 N in sitting position. Serial dynamic renal images were taken, of which data were simultaneously stored in a data processor for later analysis. The renogram was drawn setting ROI on each kidney. Peak counts (PC) of vascular phase, peak time (PT) of secretory phase and radioisotope retention rate (RR) at 10 minutes were the parameters being compared between at rest and at exercise. GFR of each kidney was determined. Blood samples were obtained at rest and at the end of exercise for the measurement of aldosterone (ALD), plasma renin activity (PRA) and catecholamines (A, NA). Exercise caused significant lowering of PC, prolongation of PT and increase in RR (10 min. counts/peak counts) both in H and N. GFR (miota/min.) during exercise was significantly lower than at rest in both H (80 +- 22 vs 93.8 +- 16.9, p<0.02) and N (84 +- 17 vs 102 +- 15, p<0.01). ALD, PRA, A and NA are all elevated during exercise both in H and N. None of the rest-exercise differences significantly differed between H and N. The data indicate the exercise induced renal dysfunction demonstrated by Tc-99m-DTPA renograms is not specified to H but can also be observed in N, which may be resulted from the common changes in H and N of GFR and humoral factors

An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

International Nuclear Information System (INIS)

Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

2010-01-01

Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

Angiotensin-converting enzyme (ACE) inhibitory potential of standardized Mucuna pruriens seed extract.

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Chaudhary, Sushil Kumar; De, Apurba; Bhadra, Santanu; Mukherjee, Pulok K

2015-01-01

Mucuna pruriens Linn. (Fabaceae) is a tropical legume, traditionally used for controlling blood pressure. Inhibition of angiotensin-converting enzyme (ACE) is one of the successful strategies for controlling hypertension. The present study evaluated the ACE inhibition potential of the standardized extract of M. pruriens seeds. Standardization of the extract and its fractions were carried out by RP-HPLC method [methanol and 1% v/v acetic acid in water (5:95 v/v)] using levodopa as a marker. The ACE inhibition activity of the extract and fractions was evaluated at different concentrations (20, 40, 60, 80, and 100 µg/mL) using the HPLC-DAD and the UV spectrophotometric method. The liberation of hippuric acid (HA) from hippuryl-L-histidyl-L-leucine (HHL) was estimated in the spectrophotometric method and RP-HPLC assay at 228 nm. Methanol extract and aqueous fraction showed a maximum activity with IC50 values of 38.44 ± 0.90 and 57.07 ± 2.90 µg/mL (RP-HPLC), and 52.68 ± 2.02 and 67.65 ± 2.40 µg/mL (spectrophotometry), respectively. The study revealed that the aqueous extract contains the highest amount of levodopa. Eventually the methanol extract showed highest ACE inhibition activity except levodopa alone. It was further observed that the inhibition was altered with respect to the change in the content of levodopa in the extract. Thus, it can be assumed that levodopa may be responsible for the ACE inhibition activity of M. pruriens seeds. It can be concluded that M. pruriens seed is a potential ACE inhibitor can be explored further as an effective antihypertensive agent.

An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

Science.gov (United States)

Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

2010-10-01

Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

Energy Technology Data Exchange (ETDEWEB)

Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

2010-10-01

Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

Integrative Metabolic Signatures for Hepatic Radiation Injury.

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Irwin Jack Kurland

Full Text Available Radiation-induced liver disease (RILD is a dose-limiting factor in curative radiation therapy (RT for liver cancers, making early detection of radiation-associated liver injury absolutely essential for medical intervention. A metabolomic approach was used to determine metabolic signatures that could serve as biomarkers for early detection of RILD in mice.Anesthetized C57BL/6 mice received 0, 10 or 50 Gy Whole Liver Irradiation (WLI and were contrasted to mice, which received 10 Gy whole body irradiation (WBI. Liver and plasma samples were collected at 24 hours after irradiation. The samples were processed using Gas Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry.Twenty four hours after WLI, 407 metabolites were detected in liver samples while 347 metabolites were detected in plasma. Plasma metabolites associated with 50 Gy WLI included several amino acids, purine and pyrimidine metabolites, microbial metabolites, and most prominently bradykinin and 3-indoxyl-sulfate. Liver metabolites associated with 50 Gy WLI included pentose phosphate, purine, and pyrimidine metabolites in liver. Plasma biomarkers in common between WLI and WBI were enriched in microbial metabolites such as 3 indoxyl sulfate, indole-3-lactic acid, phenyllactic acid, pipecolic acid, hippuric acid, and markers of DNA damage such as 2-deoxyuridine. Metabolites associated with tryptophan and indoles may reflect radiation-induced gut microbiome effects. Predominant liver biomarkers in common between WBI and WLI were amino acids, sugars, TCA metabolites (fumarate, fatty acids (lineolate, n-hexadecanoic acid and DNA damage markers (uridine.We identified a set of metabolomic markers that may prove useful as plasma biomarkers of RILD and WBI. Pathway analysis also suggested that the unique metabolic changes observed after liver irradiation was an integrative response of the intestine, liver and kidney.

Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: Effect of sex and arsenic exposure

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Huang, Madelyn C.; Douillet, Christelle; Su, Mingming; Zhou, Kejun; Wu, Tao; Chen, Wenlian; Galanko, Joseph A.; Drobná, Zuzana; Saunders, R. Jesse; Martin, Elizabeth; Fry, Rebecca C.; Jia, Wei; Stýblo, Miroslav

2016-01-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID:26883664

Influence of a polyphenol-enriched protein powder on exercise-induced inflammation and oxidative stress in athletes: a randomized trial using a metabolomics approach.

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David C Nieman

Full Text Available Polyphenol supplementation was tested as a countermeasure to inflammation and oxidative stress induced by 3-d intensified training.Water soluble polyphenols from blueberry and green tea extracts were captured onto a polyphenol soy protein complex (PSPC. Subjects were recruited, and included 38 long-distance runners ages 19-45 years who regularly competed in road races. Runners successfully completing orientation and baseline testing (N = 35 were randomized to 40 g/d PSPC (N = 17 (2,136 mg/d gallic acid equivalents or placebo (N = 18 for 17 d using double-blinded methods and a parallel group design, with a 3-d running period inserted at day 14 (2.5 h/d, 70% VO2max. Blood samples were collected pre- and post-14 d supplementation, and immediately and 14 h after the third day of running in subjects completing all aspects of the study (N = 16 PSPC, N = 15 placebo, and analyzed using a metabolomics platform with GC-MS and LC-MS.Metabolites characteristic of gut bacteria metabolism of polyphenols were increased with PSPC and 3 d running (e.g., hippurate, 4-hydroxyhippurate, 4-methylcatechol sulfate, 1.8-, 1.9-, 2.5-fold, respectively, P<0.05, an effect which persisted for 14-h post-exercise. Fatty acid oxidation and ketogenesis were induced by exercise in both groups, with more ketones at 14-h post-exercise in PSPC (3-hydroxybutyrate, 1.8-fold, P<0.05. Established biomarkers for inflammation (CRP, cytokines and oxidative stress (protein carbonyls did not differ between groups.PSPC supplementation over a 17-d period did not alter established biomarkers for inflammation and oxidative stress but was linked to an enhanced gut-derived phenolic signature and ketogenesis in runners during recovery from 3-d heavy exertion.ClinicalTrials.gov, U.S. National Institutes of Health, identifier: NCT01775384.

The effects of toluene plus noise on hearing thresholds: an evaluation based on repeated measurements in the German printing industry.

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Schäper, Michael; Seeber, Andreas; van Thriel, Christoph

2008-01-01

The ototoxicity of occupational exposure to toluene plus noise was investigated in a longitudinal study in rotogravure printing and existing findings in the literature were evaluated. The study comprised four repeated examinations during 5 years and started with 333 male workers. Lifetime weighted average exposures (LWAE) to toluene and noise were determined from individual work histories and historic recordings; recent individual exposures were measured 10 times during the study (toluene, active sampling; noise, stationary measurements). Auditory thresholds were measured with pure tone audiometry at 0.125, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 kHz. Mean LWAE exposures to toluene and noise were 45+/-17 ppm plus 82+/-7 dB(A) for high toluene exposed and 10+/-7 ppm plus 82+/-4 dB(A) for low toluene exposed subjects, mean current exposures were 26+/-20 ppm plus 81+/-4 dB(A) and 3+/-3 ppm plus 82+/-4 dB(A). Mean exposure duration was 21.3+/-6.5 years for long exposed and 5.9+/-2.2 years for short exposed subjects. Repeated measurement analyses of variance did not reveal effects of toluene intensity, exposure duration and interactions between toluene intensity and noise intensity. Noise intensity [79+/-3 dB(A) vs. 84+/-1 dB(A)] was significant for auditory thresholds. A case concept utilising developments of individual auditory thresholds did not reveal significant toluene effects. Logistic models including age, exposure duration, toluene in ambient air, current noise and either hippuric acid or ortho-cresol (o-cresol) found only age to be significant for elevated OR of high frequency hearing loss. Due to missing toluene effects, it was concluded that the threshold level for developing hearing loss as a result of occupational exposure to toluene plus noise might be above the current limit of 50 ppm toluene.

Methionine metabolism in piglets Fed DL-methionine or its hydroxy analogue was affected by distribution of enzymes oxidizing these sources to keto-methionine.

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Fang, Zhengfeng; Luo, Hefeng; Wei, Hongkui; Huang, Feiruo; Qi, Zhili; Jiang, Siwen; Peng, Jian

2010-02-10

Previous evidence shows that the extensive catabolism of dietary essential amino acids (AA) by the intestine results in decreased availability of these AA for protein synthesis in extraintestinal tissues. This raises the possibility that extraintestinal availability of AA may be improved by supplying the animal with an AA source more of which can bypass the intestine. To test this hypothesis, six barrows (35-day-old, 8.6 +/- 1.4 kg), implanted with arterial, portal, and mesenteric catheters, were fed a DL-methionine (DL-MET) or DL-2-hydroxy-4-methylthiobutyrate (DL-HMTB) diet once hourly and infused intramesenterically with 1% p-amino hippurate. Although the directly available L-MET in DL-MET diet was about 1.2-fold that in DL-HMTB diet, the net portal appearance of L-MET was not different between the two diets. Compared with the low mRNA abundance and low activity of D-2-hydroxy acid dehydrogenase (D-HADH) and l-2-hydroxy acid oxidase (L-HAOX) in the intestine, the high mRNA abundance and high activity of D-AA oxidase (D-AAOX) indicated that the intestine had a relatively higher capacity of D-MET utilization than of dl-HMTB utilization to L-MET synthesis and its subsequent metabolism. However, in contrast to the much lower D-AAOX activity (nmol/g tissue) in the stomach than in the liver and kidney, both d-HADH and L-HAOX activity in the stomach was comparable with those in the liver and/or kidney, indicating the substantial capacity of the stomach to convert DL-HMTB to L-MET. Collectively, the difference in distribution of activity and mRNA abundance of D-AAOX, D-HADH, and L-HAOX in the piglets may offer a biological basis for the similar portal appearance of L-MET between DL-MET and DL-HMTB diets, and thus may provide new important insights into nutritional efficiency of different L-MET sources.

Does the adequacy parameter Kt/V(urea reflect uremic toxin concentrations in hemodialysis patients?

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Sunny Eloot

Full Text Available Hemodialysis aims at removing uremic toxins thus decreasing their concentrations. The present study investigated whether Kt/V(urea, used as marker of dialysis adequacy, is correlated with these concentrations. Predialysis blood samples were taken before a midweek session in 71 chronic HD patients. Samples were analyzed by colorimetry, HPLC, or ELISA for a broad range of uremic solutes. Solute concentrations were divided into four groups according to quartiles of Kt/V(urea, and also of different other parameters with potential impact, such as age, body weight (BW, Protein equivalent of Nitrogen Appearance (PNA, Residual Renal Function (RRF, and dialysis vintage. Dichotomic concentration comparisons were performed for gender and Diabetes Mellitus (DM. Analysis of Variance in quartiles of Kt/V(urea did not show significant differences for any of the solute concentrations. For PNA, however, concentrations showed significant differences for urea (P<0.001, uric acid (UA, p-cresylsulfate (PCS, and free PCS (all P<0.01, and for creatinine (Crea and hippuric acid (HA (both P<0.05. For RRF, concentrations varied for β₂-microglobulin (P<0.001, HA, free HA, free indoxyl sulfate, and free indole acetic acid (all P<0.01, and for p-cresylglucuronide (PCG, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF, free PCS, and free PCG (all P<0.05. Gender and body weight only showed differences for Crea and UA, while age, vintage, and diabetes mellitus only showed differences for one solute concentration (UA, UA, and free PCS, respectively. Multifactor analyses indicated a predominant association of concentration with protein intake and residual renal function. In conclusion, predialysis concentrations of uremic toxins seem to be dependent on protein equivalent of nitrogen appearance and residual renal function, and not on dialysis adequacy as assessed by Kt/V(urea. Efforts to control intestinal load of uremic toxin precursors by dietary or other

Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in rats.

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Chu, I; Poon, R; Valli, V; Yagminas, A; Bowers, W J; Seegal, R; Vincent, R

2005-01-01

The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin-O-deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol-gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible

Biomarker Discovery Using New Metabolomics Software for Automated Processing of High Resolution LC-MS Data

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Hnatyshyn, S.; Reily, M.; Shipkova, P.; McClure, T.; Sanders, M.; Peake, D.

2011-01-01

Robust biomarkers of target engagement and efficacy are required in different stages of drug discovery. Liquid chromatography coupled to high resolution mass spectrometry provides sensitivity, accuracy and wide dynamic range required for identification of endogenous metabolites in biological matrices. LCMS is widely-used tool for biomarker identification and validation. Typical high resolution LCMS profiles from biological samples may contain greater than a million mass spectral peaks corresponding to several thousand endogenous metabolites. Reduction of the total number of peaks, component identification and statistical comparison across sample groups remains to be a difficult and time consuming challenge. Blood samples from four groups of rats (male vs. female, fully satiated and food deprived) were analyzed using high resolution accurate mass (HRAM) LCMS. All samples were separated using a 15 minute reversed-phase C18 LC gradient and analyzed in both positive and negative ion modes. Data was acquired using 15K resolution and 5ppm mass measurement accuracy. The entire data set was analyzed using software developed in collaboration between Bristol Meyers Squibb and Thermo Fisher Scientific to determine the metabolic effects of food deprivation on rats. Metabolomic LC-MS data files are extraordinarily complex and appropriate reduction of the number of spectral peaks via identification of related peaks and background removal is essential. A single component such as hippuric acid generates more than 20 related peaks including isotopic clusters, adducts and dimers. Plasma and urine may contain 500-1500 unique quantifiable metabolites. Noise filtering approaches including blank subtraction were used to reduce the number of irrelevant peaks. By grouping related signals such as isotopic peaks and alkali adducts, data processing was greatly simplified by reducing the total number of components by 10-fold. The software processes 48 samples in under 60minutes. Principle

Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study

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Armaghan Shafaei

2016-11-01

Full Text Available This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE inhibition activity of different extracts of Orthosiphon stamineus (OS leaves and their main flavonoids, namely rosmarinic acid (RA, sinensetin (SIN, eupatorin (EUP and 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF. Furthermore, to identify possible mechanisms of action based on structure–activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX: BioSolveIT’s LeadIT program. OS ethanolic extract (OS-E exhibited highest inhibition and lowest IC50 value (45.77 ± 1.17 µg/mL against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II (56.03% ± 1.26% compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.

Relevance of fruits, vegetables and flavonoids from fruits and vegetables during early life, mid-childhood and adolescence for levels of insulin-like growth factor (IGF-1) and its binding proteins IGFBP-2 and IGFBP-3 in young adulthood.

Science.gov (United States)

Krupp, Danika; Remer, Thomas; Penczynski, Katharina J; Bolzenius, Katja; Wudy, Stefan A; Buyken, Anette E

2016-02-14

The growth hormone (GH) insulin-like growth factor (IGF) axis has been linked to insulin metabolism and cancer risk. Experimental evidence indicates that the GH-IGF axis itself can be influenced by dietary flavonoids. As fruit and vegetable (FV) intake is a major source of flavonoid consumption, FV's beneficial health effects may be explained via flavonoids' influence on the GH-IGF axis, but observational evidence is currently rare. We used data from Dortmund Nutritional and Anthropometric Longitudinally Designed Study participants to analyse prospective associations between FV, fruit intake and flavonoid intake from FV (FlavFV) with IGF-1 and its binding proteins IGFBP-2 and IGFBP-3. Subjects needed to provide a fasting blood sample in adulthood (18-39 years) and at least two 3-d weighed dietary records in early life (0·5-2 years, n 191), mid-childhood (3-7 years, n 265) or adolescence (girls: 9-15 years, boys: 10-16 years, n 261). Additional analyses were conducted among those providing at least three 24-h urine samples in adolescence (n 236) to address the predictor urinary hippuric acid (HA), a biomarker of polyphenol intake. Higher fruit intake in mid-childhood and adolescence was related to higher IGFBP-2 in adulthood (P=0·03 and P=0·045). Comparable trends (P=0·045-0·09) were discernable for FV intake (but not FlavFV) in all three time windows. Similarly, higher adolescent HA excretion tended to be related (P=0·06) to higher adult IGFBP-2 levels. Regarding IGFBP-3, a marginal (P=0·08) positive association was observed with FlavFV in mid-childhood only. None of the investigated dietary factors was related to IGF-1. In conclusion, higher fruit and FV intakes during growth may be relevant for adult IGFBP-2, but probably not for IGFBP-3 or IGF-1.

Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study.

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Shafaei, Armaghan; Sultan Khan, Md Shamsuddin; F A Aisha, Abdalrahim; Abdul Majid, Amin Malik Shah; Hamdan, Mohammad Razak; Mordi, Mohd Nizam; Ismail, Zhari

2016-11-09

This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure-activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX : BioSolveIT's LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC 50 value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC 50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.

NMR-based metabonomics study on the effect of Gancao in the attenuation of toxicity in rats induced by Fuzi.

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Sun, Bo; Wang, Xubin; Cao, Ruili; Zhang, Qi; Liu, Qiao; Xu, Meifeng; Zhang, Ming; Du, Xiangbo; Dong, Fangting; Yan, Xianzhong

2016-12-04

Fuzi, the processed lateral root of Aconitum carmichaelii Debeaux, is a traditional Chinese medicine used for its analgesic, antipyretic, anti-rheumatoid arthritis and anti-inflammation effects; however, it is also well known for its toxicity. Gancao, the root of Glycyrrhiza uralensis Fisch., is often used concurrently with Fuzi to alleviate its toxicity. However, the mechanism of detoxication is still not well clear. In this study, the effect of Gancao on the metabolic changes induced by Fuzi was investigated by NMR-based metabonomic approaches. Fifty male Wistar rats were randomly divided into five groups (group A: control, group B: Fuzi decoction alone, group C: Gancao decoction alone, group D: Fuzi decoction and Gancao decoction simultaneously, group E: Fuzi decoction 5h after Gancao decoction) and urine samples were collected for NMR-based metabolic profiling analysis. Statistical analyses such as unsupervised PCA, t-test, hierarchical cluster, and pathway analysis were used to detect the effects of Gancao on the metabolic changes induced by Fuzi. The behavioral and biochemical characteristics showed that Fuzi exhibited toxic effects on treated rats (group B) and statistical analyses showed that their metabolic profiles were in contrast to those in groups A and C. However, when Fuzi was administered with Gancao, the metabolic profiles became similar to controls, whereby Gancao reduced the levels of trimethylamine N-oxide, betaine, dimethylglycine, valine, acetoacetate, citrate, fumarate, 2-ketoglutarate and hippurate, and regulated the concentrations of taurine and 3-hydroxybutyrate, resulting in a decrease in toxicity. Furthermore, important pathways that are known to be involved in the effect of Gancao on Fuzi, including phenylalanine, tyrosine and tryptophan biosynthesis, the synthesis and degradation of ketone bodies, and the TCA cycle, were altered in co-treated rats. Gancao treatment mitigated the metabolic changes altered by Fuzi administration in rats

Ammonia Nitrogen Added to Diets Deficient in Dispensable Amino Acid Nitrogen Is Poorly Utilized for Urea Production in Growing Pigs.

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Mansilla, Wilfredo D; Silva, Kayla E; Zhu, Cuilan L; Nyachoti, Charles M; Htoo, John K; Cant, John P; de Lange, Cornelis Fm

2017-12-01

Background: Including ammonia in low-crude protein (CP) diets deficient in dispensable amino acid (DAAs) increases nitrogen retention in growing pigs. Objective: We investigated the absorption and metabolism of dietary ammonia nitrogen in the portal-drained viscera (PDV) and liver of pigs fed a diet deficient in DAA nitrogen. Methods: Eight pigs with an initial mean ± SD body weight (BW) of 26.5 ± 1.4 kg were surgically fitted with 4 catheters each (portal, hepatic and mesenteric veins, and carotid artery). The pigs were fed (2.8 × 191 kcal/kg BW 0.60 ), for 7 d and every 8 h, a diet deficient in DAA nitrogen supplemented with increasing amounts of ammonia nitrogen (CP: 7.76%, 9.27%, and 10.77%; indispensable amino acid nitrogen:total nitrogen ratio: 0.71, 0.59, and 0.50 for control and low- and high-ammonia diets, respectively). The treatment sequence was based on a Latin square design with 3 consecutive periods. On the last day of each period, blood flows in the portal and hepatic veins were determined with a continuous infusion of ρ-amino hippuric acid into the mesenteric vein. Serial blood samples were taken to determine ammonia and urea nitrogen concentration. Net balances of ammonia and urea nitrogen were calculated for the PDV and liver. Results: Cumulative (8 h) ammonia nitrogen appearance in the portal vein increased ( P ≤ 0.05) with ammonia intake (433, 958, and 1629 ± 60 mg ammonia nitrogen/meal for control and low- and high-ammonia diets, respectively). The cumulative hepatic uptake of ammonia nitrogen increased ( P ≤ 0.05) with ammonia nitrogen supply. The cumulative urea nitrogen appearance in the hepatic vein tended to increase ( P ≤ 0.10) only in high-ammonia treatment (-92.5, -59.4, and 209.7 ± 92 mg urea nitrogen/meal for control and low- and high-ammonia diets, respectively) and, relative to the control diet, represented -6.0% and 11% of ammonia nitrogen intake. Conclusion: Dietary ammonia nitrogen is poorly utilized for urea

Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: patient perspectives

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Peña-Quintana L

2017-09-01

Full Text Available Luis Peña-Quintana,1–3 Marta Llarena,2 Desiderio Reyes-Suárez,2 Luis Aldámiz-Echevarria4 1Pediatric Gastroenterology, Hepatology, and Nutrition Unit, Universitario Materno-Infantil Hospital de Canarias, University of Las Palmas de Gran Canaria, 2Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, 3CIBEROBN, Madrid, 4Unit of Metabolism, Cruces University Hospital, BioCruces Health Research Institute, GCV-CIBER de Enfremedades Raras (CIBERER, Barakaldo, Spain Abstract: Urea-cycle disorders are a group of rare hereditary metabolic diseases characterized by deficiencies of one of the enzymes and transporters involved in the urea cycle, which is necessary for the removal of nitrogen produced from protein breakdown. These hereditary metabolic diseases are characterized by hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. Sodium benzoate combines with glycine and phenylacetate/phenylbutyrate with glutamine, forming, respectively, hippuric acid and phenylacetylglutamine, which are eliminated in the urine. Among the ammonia-scavenging drugs, sodium phenylbutyrate is a well-known long-term treatment of urea-cycle disorders. It has been used since 1987 as an investigational new drug, and was approved for marketing in the US in 1996 and the EU in 1999. However, sodium phenylbutyrate has an aversive odor and taste, which may compromise patients’ compliance, and many patients have reported difficulty in taking this drug. Sodium phenylbutyrate granules are a new tasteless and odor-free formulation of sodium phenylbutyrate, which is indicated in the treatment of urea-cycle disorders. This recently developed taste-masked formulation of sodium phenylbutyrate granules was designed to overcome the considerable issues that taste has on adherence to therapy. Several studies have reported the

Nuclear medicine program progress report for quarter ending March 31, 1996

Energy Technology Data Exchange (ETDEWEB)

Knapp, F.F. Jr.; Ambrose, K.R.; Beets, A.L.; Guhlke, S.; Luo, H.; McPherson, D.W.; Mirzadeh, S.; Mokler, F.

1996-10-01

Biodistribution studies with the radioiodinated 3(R)- and 3(S)-BMIPP isomers in rats have shown that 3(R)-BMIPP has 20-25% higher heart uptake (15-180 min) than 3(S)-BMIPP, while uptake in other tissues examined is similar. To evaluate the possible differences in metabolic fate of the two isomers, a mixture of [I-125]-3(R)/[I-131]- 3(S)-BMIPP was administered to fasted female Fisher rats. Groups (n=3 rats per group) were sacrificed after 15, 60 and 180 min, and urine and feces collected from another group. Samples of blood, heart, liver, lungs, kidney, and urine were Folch-extracted. The distribution of I-125 and I-131 in the organic, aqueous, and pellet samples were determined. Organic samples were then analyzed by thin-layer chromatography (TLC) and high performance liquid chromatography (HPLC). The relative distribution of I-125/I-131 in the lipid, aqueous, and pellet samples was similar for both isomers. Distribution of I-125/I-131 in the various components of the lipid extracts observed by TLC was similar, with principal incorporation into the free fatty acid (FFA) and triglyceride (TG) pools. HPLC analyses (Cl8) of the FFA fraction showed similar I-125/I-131 profiles, corresponding to BMIPP, and the {alpha}-methyl-C,4 (PIPA) and C12, Cl0 and C6 carbon chain-length catabolites. By TLC, urine I-125/I-131 chromatographed with hippuric acid. HPLC analyses (Cl 8) of acid-hydrolyzed urine gave a single I-125/I-131 component with the same RRT as 2-({beta}-iodophenyl)acetic acid, the final {alpha}/{beta}-oxidative BMIPP catabolite. Unexpectedly, HPLC of lipids from base hydrolyzed TG from the heart tissue, showed I-125/I-125 co-chromatographing with short-chain fatty acids, with only levels in BMIPP. These unexpected results demonstrate that the 3(R)-BMIPP and 3(S)-BMIPP isomers are metabolized similarly in rat tissues, and that the higher myocardial extraction observed for the 3(R)-BMIPP may reflect differences in the relative membrane transport of the two isomers.

Hepatotoxic constituents and toxicological mechanism of Xanthium strumarium L. fruits.

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Xue, Li-Ming; Zhang, Qiao-Yan; Han, Ping; Jiang, Yi-Ping; Yan, Rong-Di; Wang, Yang; Rahman, Khalid; Jia, Min; Han, Ting; Qin, Lu-Ping

2014-03-14

In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This paper is in an attempt to identify the hepatotoxic components in Xanthium strumarium L. fruits (XSF) and interpret the toxicological mechanism induced by XSF. XSF extract was prepared and seven characteristic components were isolated and identified in XSF water extracts. We evaluated their hepatotoxicity effect on cell proliferation and lactate dehydrogenase (LDH) activity in L-02 and BRL liver cell line. An integrated metabonomics study using high-resolution (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy combined with multivariate statistical analysis was undertake to elucidate the hepatotoxicity mechanism induced in rats by XSF. The urine and serum metabolites were measured after treatment of rats with XSF (7.5, 15.0 and 30.0 g/kg/day) for 5 days. The results showed that atractyloside, carboxyatractyloside, 4'-desulphate-atractyloside and XSF induced significant cytotoxic effects in both L-02 and BRL liver cell lines, indicating that atractyloside, carboxyatractyloside, and 4'-desulphate-atractyloside were the toxic components of XSF. When rats were treated with XSF at 30.0 g/kg the hepatotoxicity was reflected in the changes observed in serum biochemical profiles and by the histopathological examination of the liver. The levels of VLDL/LDL, 3-HB, lactate, acetate, acetone and glutamate in serum were increased in this group, while d-glucose, choline and valine were decreased. The elevation in the levels of succinate, citrate, 2-oxo-glutamate, glycine, 3-HB, acetate, lactate, hippurate, dimethylglycine, methylamine, dimethylamine, phenylalanine and tryptophan was observed in urine, in contrast a reduction in the intensities of taurine, d-glucose, N-acetyl-glucoprotein and trimethylamine

Pasture Feeding Changes the Bovine Rumen and Milk Metabolome

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Tom F. O’Callaghan

2018-04-01

. CLV feeding resulted in increased concentrations of milk urea. Milk from pasture-based feeding systems was shown to have significantly higher concentrations of hippuric acid, a potential biomarker of pasture-derived milk. This study has demonstrated that 1H-NMR metabolomics coupled with multivariate analysis is capable of distinguishing both rumen-fluid and milk derived from cows on different feeding systems, specifically between indoor TMR and pasture-based diets used in this study.

Comprehensive Biological Monitoring to Assess Isocyanates and Solvents Exposure in the NSW Australia Motor Vehicle Repair Industry.

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Hu, Jimmy; Cantrell, Phillip; Nand, Aklesh

2017-10-01

Urethane products that contain isocyanates are extensively used in the motor vehicle repair (MVR) industry and other industries such as furniture and cabinet-making as two-pack spray paints, clears, and adhesives. Attention has recently been refocussed on isocyanate-containing chemicals, particularly in paints. The spray painters in the MVR industry had a propensity to develop industrial asthma at a rate 80 times higher than the general public, which was previously reported in the UK. To track workers exposure to isocyanates, urine samples were collected from 196 spray painters who worked mainly in 78 MVR shops across 54 New South Wales (NSW) towns and suburbs. The biological monitoring also covered exposure testing to a wide variety of solvents including aromatic hydrocarbons, ketones, and alcohols. The main finding of the study was that 2.6% of the spray painters surveyed in the MVR industry in NSW that handled isocyanate-containing paints showed exposure to isocyanates; with 1.0% being moderately exposed, which is more than twice the current UK's Health and Safety Executive (HSE) Biological Monitoring Guidance Value (BMGV) of 1 µmol mol-1 creatinine. Potential exposures to toluene (a solvent often found in paint thinners) was monitored via hippuric acid (HA) urine levels and showed 2.6% of the spray painters surveyed to be over the US' American Conference of Government Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) of 1010 mmol/mole creatinine for HA. The other solvents or their metabolites were all below their respective BEI; these comprised benzene, xylene, ethyl benzene, methyl ethyl ketone, acetone, methanol, and ethanol. These findings indicate that isocyanates and certain solvents exposure were occurring in the NSW Australia vehicle repair industry, albeit at lower levels than previous occupational biological monitoring studies that showed higher exposure levels, particularly for isocyanates. One reason for this could be the increasing use

Preparation, characterization and biological evaluation of fac(M(CO)3)+ labeled amino carboxy ligands

International Nuclear Information System (INIS)

Baishya, Rinku; Halder, K.K.; Debnath, M.C.

2010-01-01

Full text: The objective of this study is to radiolabel various amino carboxy based chelating ligands with fac(M(CO) 3 )+ core, their physicochemical and biological characterization so that they can be used as bifunctional chelators and could be incorporated into biomolecules. Introduction: Amino acids as a class attract considerable physiological interest because of their participation in many vital processes associated with the living system. Some amino acids express in some particular organ like glutamic acid acts as excitatory neurotransmitter in mammalian brain. Histidine, methionine, tryptophan express in the tumor cell. Amino acids also play an important role for development of a new series of chelate complexes of 99m Tc that can direct the biodistribution of the radiotracer for purposes in diagnostic nuclear medicine. Various 99m Tc-amino acid chelates based on (Tc(V)O) 3 + core were reported from this laboratory some of which exhibited high renal specificity in animals. The structural requirements favouring this biological behaviour could be the oxotechnetium glycine sequence (TcO-NH-CH 2 -COOH) resembling the -CO-glycine sequence of hippurate. In recent years with the development of organometallic chemistry of technetium and rhenium for biological application intensive efforts have been executed on designing of the bifunctional chelator for effective coordination to (M(CO) 3 )+ core. The suitability and stability of the metal carbonyl core has given rise to a new platform for the preparation of the metal complexes of biologically active peptide in macroscopic quantity using the solid phase synthetic approach. Materials and Methods: We chelated different amino carboxy based ligands with ( 99m Tc(CO) 3 )+ and (Re(CO) 3 )+ core. The choice of amino acid was made by taking representative members from various groupings such as mono amino mono carboxylate, mono amino poly carboxylate, poly amino mono carboxylate and sulfur containing amino carboxylates. The

Probiotics for preventing urinary tract infection in people with neuropathic bladder.

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Toh, Swee-Ling; Boswell-Ruys, Claire L; Lee, Bon San B; Simpson, Judy M; Clezy, Kate R

2017-09-08

Neuropathic or neurogenic bladder describes a process of dysfunctional voiding as the result of injury in the brain, spinal cord or nerves innervating the bladder. People with neuropathic bladder, such as from spinal cord injury (SCI), are at significant risk of morbidity from urinary tract infections (UTI). Effective methods to prevent UTI in people with SCI have been sought for many years. Probiotics (micro-organisms that exert beneficial health effects in the host) have been recommended for bacterial interference of the urological tract to reduce colonisation by uropathogen and to manage the dual problems of infection and antibiotic resistance. This review looked at the benefits and harms of probiotics in preventing symptomatic UTI in people with neuropathic bladder compared with placebo, no therapy, or non-antibiotic prophylaxis (cranberry juice, methenamine hippurate, topical oestrogen). We searched the Cochrane Kidney and Transplant Specialised Register up to 10 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. All randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs looking at the use of probiotics for the prophylaxis of UTI in people with neuropathic bladders was considered for inclusion. Men, women and children of all ages with neuropathic bladders from neurological injury such as suprapontine, supra sacral and sacral aetiologies was included. All bladder management types, including reflex voiding, time voiding, indwelling and intermittent catheterization were eligible for this review.Studies comparing probiotics to placebo, no treatment or other non-antibiotic prophylaxis was included. Studies comparing probiotics with antibiotics or in combination with antibiotics were

Cranberries for preventing urinary tract infections

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Ruth G. Jepson

Full Text Available BACKGROUND: Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs. This is the third update of our review first published in 1998 and updated in 2004 and 2008. OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. METHODS: Search methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies. Date of search: July 2012. Selection criteria: All randomised controlled trials (RCTs or quasi-RCTs of cranberry products for the prevention of UTIs. Data collection and analysis: Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy. Risk ratios (RR were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool. MAIN RESULTS: This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants evaluated only cranberry juice/concentrate; nine studies (1032 participants evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta