A pilot study of the effect of human breast milk on urinary metabolome analysis in infants.

PubMed

Shoji, Hiromichi; Taka, Hikari; Kaga, Naoko; Ikeda, Naho; Kitamura, Tomohiro; Miura, Yoshiki; Shimizu, Toshiaki

2017-08-28

This study aimed to examine the nutritional effect of breast feeding on healthy term infants by using urinary metabolome analysis. Urine samples were collected from 19 and 14 infants at 1 and 6 months, respectively. Infants were separated into two groups: the breast-fed group receiving <540 mL/week of their intake from formula (n=13 at 1 month; n=9 at 6 months); and the formula-fed group receiving no breast milk (BM) (n=6 at 1 month; n=5 at 6 months). Urinary metabolome analysis was performed using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS). A total of 29 metabolites were detected by CE-TOF/MS metabolome analysis in all samples. Urinary excretion of choline metabolites (choline base solution, N,N-dimethylglycine, sarcosine, and betaine) at 1 month were significantly (p<0.05) higher in breast-fed infants than in formula-fed infants. However, choline metabolites were not significantly different between the groups at 6 months. Urinary excretion of lactic acid in breast-fed infants at 1 and 6 months was significantly lower than that in formula-fed infants. Urinary l(-)-threonine and l-carnosine excretion at 1 month was significantly lower in breast-fed infants than in formula-fed infants, but it was not significantly different between the groups at 6 months. The type of feeding in early infancy affects choline metabolism, as well as lactate, threonine, and carnosine levels, in healthy term infants. Urinary metabolome analysis by the CE-TOF/MS method is useful for assessing nutritional metabolism in infants.

Updated bioavailability and 48 h excretion profile of flavan-3-ols from green tea in humans.

PubMed

Calani, Luca; Del Rio, Daniele; Luisa Callegari, Maria; Morelli, Lorenzo; Brighenti, Furio

2012-08-01

Green tea is a popular beverage, prepared with infusion of unfermented dried leaves of Camellia sinensis, and is one of the most relevant sources of polyphenolic compounds in the human diet. This study reports green tea flavan-3-ol absorption, metabolism and complete urinary excretion up to 48 h in 20 healthy volunteers. Urinary and tea samples were analysed by high-performance liquid chromatography coupled with tandem mass spectrometry. Green tea contained monomeric flavan-3-ols and proanthocyanidins with a total polyphenol content of 728 μmol. A total of 41 metabolites were identified in urines, all present in conjugated forms. Among these, six colonic metabolites of green tea flavan-3-ols were identified for the first time after green tea consumption in humans. The average 48 h bioavailability was close to 62%, major contributors being microbial metabolites. Some volunteer showed a 100% absorption/excretion, whereas some others were unable to efficiently absorb/excrete this class of flavonoids. This suggests that colonic ring fission metabolism could be relevant in the putative bioactivity of green tea polyphenols.

Characterization of urinary metabolites of testosterone, methyltestosterone, mibolerone and boldebone in greyhound dogs.

PubMed

Williams, T M; Kind, A J; Hyde, W G; Hill, D W

2000-06-01

Androgenic steroids are used in female greyhound dogs to prevent the onset of estrus; moreover, these steroids also have potent anabolic activity. As anabolic steroids increase muscle mass and aggression in animals, the excessive use of these agents in racing greyhounds gives an unfair performance advantage to treated dogs. The biotransformation of most anabolic steroids has not been determined in greyhound dogs. The objective of the present study was to identify the urinary metabolites of testosterone, methyltestosterone, mibolerone, and boldenone in greyhound dogs. These steroids were administered orally (1 mg/kg) to either male or female greyhound dogs and urine samples were collected pre-administration and at 2, 4, 8, 12, 24, 72, and 96 h post-administration. Urine extracts were analyzed by high-performance liquid chromatography/mass spectrometry (HPLC/MS) to identify major metabolites and to determine their urinary excretion profiles. Major urinary metabolites, primarily glucuronide, conjugated and free, were detected for the selected steroids. Sulfate conjugation did not appear to be a major pathway for steroid metabolism and excretion in the greyhound dog. Phase I biotransformation was also evaluated using greyhound dog liver microsomes from untreated dogs. The identification of several in vivo steroid metabolites generated in this study will be useful in detecting these steroids in urine samples submitted for drug screening.

ESTIMATES OF AGE-SPECIFIC URINARY EXCRETION RATES FOR CREATININE AMONG CHILDREN

EPA Science Inventory

The results of this study suggest that naïve adjustment by creatinine concentration, without consideration of the age-dependence of the physiological mechanisms controlling its excretion, may introduce sizeable error and is inappropriate when comparing metabolite concentrations a...

TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN C57BL/6 MICE FOLLOWING SUBCHRONIC EXPOSURE TO ARSENATE (ASV) IN DRINKING WATER

EPA Science Inventory

The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent metabolites hav...

Estimation of caffeine intake from analysis of caffeine metabolites in wastewater.

PubMed

Gracia-Lor, Emma; Rousis, Nikolaos I; Zuccato, Ettore; Bade, Richard; Baz-Lomba, Jose Antonio; Castrignanò, Erika; Causanilles, Ana; Hernández, Félix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; van Nuijs, Alexander L N; Plósz, Benedek G; Ramin, Pedram; Ryu, Yeonsuk; Santos, Miguel M; Thomas, Kevin; de Voogt, Pim; Yang, Zhugen; Castiglioni, Sara

2017-12-31

Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further information is needed to standardize this approach. Wastewater analysis proved useful to providing additional local information on caffeine use. Copyright © 2017 Elsevier B.V. All rights reserved.

TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ACUTE ORAL ADMINISTRATION OF ARSENATE

EPA Science Inventory

ABSTRACT The relationship of exposure dose and tissue concentration of parent chemical and metabolites is a critical issue in cases where toxicity may be mediated by a metabolite or parent chemical and metabolite acting together. This has emerged as an issue for inorganic ars...

Individual variability in the human metabolism of an arsenic-containing carbohydrate, 2',3'-dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-beta-D-riboside, a naturally occurring arsenical in seafood.

PubMed

Raml, Reingard; Raber, Georg; Rumpler, Alice; Bauernhofer, Thomas; Goessler, Walter; Francesconi, Kevin A

2009-09-01

We report studies on the variability in human metabolism of an oxo-arsenosugar involving the ingestion of a chemically synthesized arsenosugar and quantitative determination of the arsenic metabolites in urine and serum by HPLC coupled with arsenic-selective mass spectrometric detection (ICPMS, inductively coupled plasma mass spectrometry). The total, four-day, urinary excretion of arsenic for six volunteers ranged widely from ca. 4-95%. The arsenic metabolites present in the urine also showed great variability: high arsenic excretion was accompanied by almost complete biotransformation of the ingested oxo-arsenosugar into a multitude of metabolites (>10), whereas the subjects that excreted low amounts of arsenic produced low quantities of metabolites relative to unchanged oxo-arsenosugar and its thio-analogue. Major arsenic urinary metabolites were dimethylarsinate (DMA) and possible intermediates in the degradation of arsenosugar to DMA, namely, dimethylarsinoylethanol (DMAE) and dimethylarsinoylacetate (DMAA) present both as their oxo- and thio-analogues. Thio-DMAE and thio-DMAA were also found in blood serum indicating that these species were formed in the liver rather than on storage of the urine in the bladder. The large variability in the way individuals metabolize arsenosugars has implications for risk assessment of arsenic intake from seafood.

Human metabolism and excretion kinetics of aniline after a single oral dose.

PubMed

Modick, Hendrik; Weiss, Tobias; Dierkes, Georg; Koslitz, Stephan; Käfferlein, Heiko Udo; Brüning, Thomas; Koch, Holger Martin

2016-06-01

Aniline is an important source material in the chemical industry (e.g., rubber, pesticides, and pharmaceuticals). The general population is known to be ubiquitously exposed to aniline. Thus, assessment of aniline exposure is of both occupational and environmental relevance. Knowledge on human metabolism of aniline is scarce. We orally dosed four healthy male volunteers (two fast and two slow acetylators) with 5 mg isotope-labeled aniline, consecutively collected all urine samples over a period of 2 days, and investigated the renal excretion of aniline and its metabolites by LS-MS/MS and GC-MS. After enzymatic hydrolysis of glucuronide and sulfate conjugates, N-acetyl-4-aminophenol was the predominant urinary aniline metabolite representing 55.7-68.9 % of the oral dose, followed by the mercapturic acid conjugate of N-acetyl-4-aminophenol accounting for 2.5-6.1 %. Acetanilide and free aniline were found only in minor amounts accounting for 0.14-0.36 % of the dose. Overall, these four biomarkers excreted in urine over 48 h post-dose represented 62.4-72.1 % of the oral aniline dose. Elimination half-times were 3.4-4.3 h for N-acetyl-4-aminophenol, 4.1-5.5 h for the mercapturic acid conjugate, and 1.3-1.6 and 0.6-1.2 h for acetanilide and free aniline, respectively. Urinary maximum concentrations of N-acetyl-4-aminophenol were reached after about 4 h and maximum concentrations of the mercapturic acid conjugate after about 6 h, whereas concentrations of acetanilide and free aniline peaked after about 1 h. The present study is one of the first to provide reliable urinary excretion factors for aniline and its metabolites in humans after oral dosage, including data on the predominant urinary metabolite N-acetyl-4-aminophenol, also known as an analgesic under the name paracetamol/acetaminophen.

Rat urinary metabolites of [9,10-methylene-14C] sterculic acid.

PubMed

Eisele, T A; Yoss, J K; Nixon, J E; PAwlowski, N E; Libbey, L M; Sinnhuber, R O

1977-07-20

1. The metabolism of [9,10-methylene-14C] sterculic acid was studied in corn oil and Stercula foetida oil fed rats. The majority of the radioactivity was excreted into the urine as short chain dicarboxylic acids. The main urinary metabolites were cis-3,4-methylene adipic acid, cis-3,4-methylene suberic acid, trans-3,4-methylene adipic acid, cis-3,4-methylene pimelic acid, and cis-3,4-methylene azelic acid. 2. Formation of these urinary metabolites requires alpha-, beta-, and omega-oxidation plus reduction of the cyclopropene ring to a cyclopropane ring. Sterculic acid must be transported through both mitochondrial and microsomal systems. 3. Other non-radioactive urinary compounds were also identified. A proposed pathway for the metabolism of sterculic acid and possible detrimental effects caused by these metabolites is discussed.

Tissue Distribution And Urinary Excretion Of Inorganic Arsenic And Its Methylated Metabolites In C57BL6 Mice Following Subchronic Exposure To Arsenate In Drinking Water

EPA Science Inventory

The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for As^V because its trivalent meta...

Metabolism of boldenone in man: gas chromatographic/mass spectrometric identification of urinary excreted metabolites and determination of excretion rates.

PubMed

Schänzer, W; Donike, M

1992-01-01

Urinary metabolites of boldenone (androsta-1,4-dien-17 beta-ol-3-one) following oral administration of boldenone (doses from 11 to 80 mg) to man were isolated from urine via XAD-2 adsorption and enzymatic hydrolysis with beta-glucuronidase from Escherichia coli. The isolated metabolites were derivatized with N-methyl-N-trimethylsilyltri- fluoroacetamide/trimethyliodosilane and analysed by gas chromatography/mass spectrometry with electron impact (EI) ionization at 70 eV. Boldenone (I) and four metabolites were identified after hydrolysis of the urine with beta-glucuronidase: 5 beta-androst-1-en-17 beta-ol-3-one (II), 5 beta-androst-1-ene-3 alpha, 17 beta-diol (III), 5 beta-androst-1-en-3 alpha-ol-17-one (IV) and 5 beta-androst-1-en-6 beta-ol-3,17-dione (V). Five further metabolites in low concentration were identified without enzymatic hydrolysis after treatment of the urine with potassium carbonate: 5 beta-androst-1-ene-3,17-dione (VI), 5 alpha-androst-1-ene-3,17-dione (VII), androsta-1,4-diene-3,17-dione (VIII), androsta-1,4-diene-6 beta,17 beta-diol-3-one (IX) and androsta-1,4-dien-6 beta-ol-3,17-dione (X). The identification of the metabolites is based on the gas chromatography retention index, high-performance liquid chromatography retention, EI mass spectrum, chemical reactions of the isolated metabolites, and synthesis of metabolites II, III, IV, VI and VII. The EI mass spectra of the bis-trimethylsilyl derivatives of boldenone and its metabolites display all intense molecular ions, M-15 ions and fragment ions originating from cleavage of the B-ring. The excreted metabolites can be separated in basic extractable labile conjugates and in stable conjugates. More than 95% of metabolites are excreted as stable conjugates.

Raised urinary glucocorticoid and adrenal androgen precursors in the urine of young hypertensive patients: possible evidence for partial glucocorticoid resistance

PubMed Central

Shamim, W; Yousufuddin, M; Francis, D; Gualdiero, P; Honour, J; Anker, S; Coats, A

2001-01-01

OBJECTIVE—To evaluate urinary glucocorticoid excretion profiles in a cohort of recently diagnosed young hypertensive patients.
METHODS—After excluding patients with secondary causes, 60 individuals with premature hypertension were recruited (diagnosed by ambulatory blood pressure monitoring before the age of 36 years). In addition, 30 older hypertensive controls (age of onset > 36 years, "middle aged hypertensive controls"), and 30 normal controls (age matched to the young hypertensive group) were studied. All provided 24 hour urine collections for mass spectrometry for total cortisol metabolites and total androgen metabolites by gas chromatography.
RESULTS—Among male patients, those with premature hypertension had higher total urinary excretion of cortisol metabolites (mean (SD), 13 332 (6472) µg/day) than age matched normal controls (7270 (1788) µg/day; p = 0.00001) or middle aged hypertensive controls (8315 (3565) µg/day; p = 0.002). A similar increase was seen among the female patients, although the absolute concentrations were lower. There was no significant difference between middle aged hypertensive patients and normal controls. Urinary total androgen excretion profiles in female patients also showed an unusual increase in the premature hypertension group (2958 (1672) µg/day) compared with the other groups (middle aged hypertensive controls, 1373 (748) µg/day, p = 0.0003; normal controls, 1687 (636) µg/day, p = 0.002). In all subjects, serum sodium and creatinine concentrations were within the normal range; serum potassium concentrations were found to be low before the start of treatment.
CONCLUSIONS—Individuals presenting with premature hypertension have an abnormally high excretion of glucocorticoid metabolites in the urine. While the mechanism remains uncertain, these findings are compatible with partial resistance of the glucocorticoid receptors, with a compensatory increase in cortisol and androgen metabolites. The mineralocorticoid effects of the latter (sodium and water retention) may contribute to an abnormally high blood pressure and may have implications for targeted selection of first line treatment in young hypertensive patients.


Keywords: premature hypertension; glucocorticoid resistance; cortisol metabolites; glucocorticoid receptor resistance PMID:11454825

Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients.

PubMed

Di Lorenzo, G; Pacor, M L; Vignola, A M; Profita, M; Esposito-Pellitteri, M; Biasi, D; Corrocher, R; Caruso, C

2002-12-01

The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine. For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients. Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

Formic acid excretion in rats exposed to trichloroethylene: a possible explanation for renal toxicity in long-term studies.

PubMed

Green, T; Dow, J; Foster, J R; Hext, P M

1998-05-15

Rats exposed to trichloroethylene, either by gavage or by inhalation, excreted large amounts of formic acid in urine which was accompanied by a change in urinary pH, increased excretion of ammonia, and slight increases in the excretion of calcium. Following a single 6-h exposure to 500 ppm trichloroethylene, the excretion of formic acid was comparable to that seen after a 500 mg/kg dose of formic acid itself, yet the half-life was markedly different. Formate excretion in trichloroethylene treated rats reached a maximum on day 2 and had a half-life of 4-5 days, whereas urinary excretion was complete within 24 h following a single dose of formic acid itself. Formic acid was shown not to be a metabolite of trichloroethylene. When rats were exposed to 250 or 500 ppm trichloroethylene, 6 h/day, for 28 days, the only significant effects were increased formic acid and ammonia excretion, and a change in urinary pH. There was no evidence of morphological liver or kidney damage. Long-term exposure to formic acid is known to cause kidney damage suggesting that excretion of this acid may contribute to the kidney damage seen in the long-term studies with trichloroethylene.

GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh.

PubMed

Rodrigues, Ema G; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C

2012-05-01

We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individuals without skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid urinary concentrations, whereas wild-type AS3MT rs11191439 had significantly lower levels of As(III) and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion.

Hormonal changes during 17 days of head-down bed-rest

NASA Technical Reports Server (NTRS)

Custaud, Marc-Antoine; Arnaud, Sara B.; Monk, Timothy H.; Claustrat, Bruno; Gharib, Claude; Gauquelin-Koch, Guillemette

2003-01-01

We investigated in six men the impact of 17 days of head-down bed rest (HDBR) on the daily rhythms of the hormones involved in hydroelectrolytic regulation. This HDBR study was designed to mimic a real space flight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of Growth Hormone (GH), Cortisol, 6 Sulfatoxymelatonin, Normetadrenaline (NMN) and Metadrenaline (NM) was determined. A decrease in urinary cortisol excretion during the night of HDBR was noted. For GH, a rhythm was found before and during HDBR. The rhythm of melatonin, evaluated with the urine excretion of 6 Sulfatoxymelatonin (aMT6S), the main hepatic metabolite, persisted throughout the experiment without any modification to the level of phase. A decrease during the night was noted for normetadrenaline urinary derivates, but only during the HDBR.

Profiling of urinary bile acids in piglets by a combination of enzymatic deconjugation and targeted LC-MRM-MS

USDA-ARS?s Scientific Manuscript database

Bile acids (BAs) have an important role in the control of fat, glucose and cholesterol metabolism. Synthesis of bile acids is the major pathway for the metabolism of cholesterol and for the excretion of excess cholesterol in mammals. Bile acid intermediates and/or their metabolites are excreted in...

Antiadhesive Activity and Metabolomics Analysis of Rat Urine after Cranberry (Vaccinium macrocarpon Aiton) Administration.

PubMed

Peron, Gregorio; Pellizzaro, Anna; Brun, Paola; Schievano, Elisabetta; Mammi, Stefano; Sut, Stefania; Castagliuolo, Ignazio; Dall'Acqua, Stefano

2017-07-19

Cranberry (Vaccinium macrocarpon Aiton) is used to treat noncomplicated urinary tract infections (UTIs). A-type procyanidins (PAC-A) are considered the active constituents able to inhibit bacterial adhesion to the urinary epithelium. However, the role of PAC-A in UTIs is debated, because of their poor bioavailability, extensive metabolism, limited knowledge about urinary excretion, and contradictory clinical trials. The effects of 35-day cranberry supplementation (11 mg/kg PAC-A, 4 mg/kg PAC-B) were studied in healthy rats using a ultra performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach. Microbial PAC metabolites, such as valeric acid and valerolactone derivatives, were related to cranberry consumption. An increased urinary excretion of glucuronidated metabolites was also observed. In a further experiment, urine samples were collected at 2, 4, 8, and 24 h after cranberry intake and their antiadhesive properties were tested against uropathogenic Escherichia coli. The 8 h samples showed the highest activity. Changes in urinary composition were studied by ultra performance liquid chromatography-time-of-flight (UPLC-QTOF), observing the presence of PAC metabolites. The PAC-A2 levels were measured in all collected samples, and the highest amounts, on the order of ng/mL, were found in the samples collected after 4 h. Results indicate that the antiadhesive activity against uropathogenic bacteria observed after cranberry consumption is ascribable to PAC-A metabolites rather than to a direct PAC-A effect, as the measured PAC-A levels in urine was lower than those reported as active in the literature.

Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus.

PubMed

Nielsen, S E; Breinholt, V; Cornett, C; Dragsted, L O

2000-09-01

The present study was carried out in order to investigate the in vivo biotransformation and excretion of the flavone, tangeretin, found in citrus fruits, by analysing urine and faeces samples from rats after repeated administration of 100 mg/kg body weight/day tangeretin. The formed metabolites were separated and identified by HPLC and the structures elucidated by LC/MS and 1H NMR. Ten new, major metabolites with intact flavonoid structure were identified. The metabolites identified were either demethylated or hydroxylated derivatives of the parent compound and metabolic changes were found primarily to occur in the 4' position of the B-ring. The total urinary excretion of tangeretin metabolites with intact flavan nucleus was about 11% of the administered daily dose.

Urinary excretion of the metabolites of n-hexane and its isomers during occupational exposure.

PubMed Central

Perbellini, L; Brugnone, F; Faggionato, G

1981-01-01

Environmental exposure to commercial hexane (n-hexane, 2-methylpentane, and 3-methylpentane) was tested in several work places in five shoe factories by taking three grap-air samples during the afternoon shift. Individual exposure ranges were 32-500 mg/m3 for n-hexane, 11-250 mg/m3 for 2-methylpentane, and 10-204 mg/m3 for 3-methylpentane. The metabolites of commercial hexane in the urine of 41 workers were measured at the end of the work shift. 2-Hexanol, 2,5-hexanedione, 2,5-dimethylfuran, and gamma-valerolactone were found as n-hexane metabolites and 2-methyl-2-pentanol and 3-methyl-2-pentanol as 2-methylpentane and 3-methylpentane metabolites. The presence of metabolites in the urine was correlated with occupational exposure to solvents. n-Hexane exposure was correlated more positively with 2-hexanol and 2,5-hexanedione than with 2,5-dimethylfuran and gamma-valerolactone. A good correlation was also found between total n-hexane metabolites and n-hexane exposure. 2-Methyl-2-pentanol and 3-methyl-2-pentanol were highly correlated with 2-methylpentane and 3-methylpentane exposure. The results suggest that the urinary excretion of hexane metabolites may be used for monitoring occupational exposure to n-hexane and its isomers. PMID:7470400

Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction.

PubMed

Delemarre, F M; Thomas, C M; van den Berg, R J; Jongsma, H W; Steegers, E A

2000-10-01

Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy. In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls. In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy. Copyright 2000 Harcourt Publishers Ltd.

Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone.

PubMed

Farley, Sherry M; Leonard, Scott W; Labut, Edwin M; Raines, Hannah F; Card, David J; Harrington, Dominic J; Mustacich, Debbie J; Traber, Maret G

2012-06-01

The mechanism for increased bleeding and decreased vitamin K status accompanying vitamin E supplementation is unknown. We hypothesized that elevated hepatic α-tocopherol (α-T) concentrations may stimulate vitamin K metabolism and excretion. Furthermore, α-T may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4). In order to investigate these hypotheses, rats were fed phylloquinone (PK) or menadione (MN) containing diets (2 μmol/kg) for 2.5 weeks. From day 10, rats were given daily subcutaneous injections of either α-T (100 mg/kg) or vehicle and were sacrificed 24 h after the seventh injection. Irrespective of diet, α-T injections decreased MK-4 concentrations in brain, lung, kidney, and heart; and PK in lung. These decreases were not accompanied by increased excretion of urinary 5C- or 7C-aglycone vitamin K metabolites, however, the urinary α-T metabolite (α-CEHC) increased ≥ 100-fold. Moreover, α-T increases were accompanied by downregulation of hepatic cytochrome P450 expression and modified expression of tissue ATP-binding cassette transporters. Thus, in rats, high tissue α-T depleted tissue MK-4 without significantly increasing urinary vitamin K metabolite excretion. Changes in tissue MK-4 and PK levels may be a result of altered regulation of transporters. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chronic administration of a microencapsulated probiotic enhances the bioavailability of orange juice flavanones in humans.

PubMed

Pereira-Caro, Gema; Oliver, Christine M; Weerakkody, Rangika; Singh, Tanoj; Conlon, Michael; Borges, Gina; Sanguansri, Luz; Lockett, Trevor; Roberts, Susan A; Crozier, Alan; Augustin, Mary Ann

2015-07-01

Orange juice (OJ) flavanones are bioactive polyphenols that are absorbed principally in the large intestine. Ingestion of probiotics has been associated with favorable changes in the colonic microflora. The present study examined the acute and chronic effects of orally administered Bifidobacterium longum R0175 on the colonic microflora and bioavailability of OJ flavanones in healthy volunteers. In an acute study volunteers drank OJ with and without the microencapsulated probiotic, whereas the chronic effects were examined when OJ was consumed after daily supplementation with the probiotic over 4 weeks. Bioavailability, assessed by 0-24h urinary excretion, was similar when OJ was consumed with and without acute probiotic intake. Hesperetin-O-glucuronides, naringenin-O-glucuronides, and hesperetin-3'-O-sulfate were the main urinary flavanone metabolites. The overall urinary excretion of these metabolites after OJ ingestion and acute probiotic intake corresponded to 22% of intake, whereas excretion of key colon-derived phenolic and aromatic acids was equivalent to 21% of the ingested OJ (poly)phenols. Acute OJ consumption after chronic probiotic intake over 4 weeks resulted in the excretion of 27% of flavanone intake, and excretion of selected phenolic acids also increased significantly to 43% of (poly)phenol intake, corresponding to an overall bioavailability of 70%. Neither the probiotic bacterial profiles of stools nor the stool moisture, weight, pH, or levels of short-chain fatty acids and phenols differed significantly between treatments. These findings highlight the positive effect of chronic, but not acute, intake of microencapsulated B. longum R0175 on the bioavailability of OJ flavanones. Copyright © 2015 Elsevier Inc. All rights reserved.

Biomonitoring of polycyclic aromatic compounds in the urine of mining workers occupationally exposed to diesel exhaust.

PubMed

Seidel, Albrecht; Dahmann, Dirk; Krekeler, Horst; Jacob, Juergen

2002-02-01

Diesel exhaust is considered a probable human carcinogen by the IARC. Biomonitoring of workers occupationally exposed to diesel exhaust was performed to determine their internal burden of diesel associated aromatic compounds. Personal air sampling also allowed to determine the exposure of the miners at their work place towards several polycyclic aromatic hydrocarbons (PAH) and nitro-arenes, the latter of which are thought to be specific constituents of diesel exhaust. For biomonitoring the urine of 18 underground salt miners was collected during and after their shift for 24-hours. half of the 18 miners were smokers. The urinary levels of 1-hydroxypyrene and hydroxylated phenanthrene metabolites were determined as biomarkers of PAH exposure, whereas urinary levels of some aromatic amines were chosen to monitor exposure towards specific nitro-arenes from diesel exhaust like 1-nitropyrene and 3-nitrobenzanthrone and to monitor the human burden by these compounds from inhaled cigarette smoke. Non-smoking workers exposed to diesel exhaust excrete an average level of about 4 micrograms phenanthrene metabolites, whereas the urinary levels in smokers were up to 3-fold higher. In summary the results indicate that (i) diesel exposure led to an increase of PAH metabolism in the workers examined, most probably by an induction of cytochrome P450 (ii) smokers could be identified in accordance with earlier studies by their increased ratio of phenanthrene metabolites derived from 1,2- and 3,4-oxidation and their higher amounts of excreted 1-naphthylamine, and (iii) the excreted amounts of aromatic amines found as metabolites of the nitro-arenes were about 5- to 10-fold higher as one might expect from the levels determined by personal air sampling at the workplace of the individuals.

[Gas chromatographic/mass spectrometric analysis of boldenone urinary metabolites in man].

PubMed

Zhang, J; Liu, C S; Zhou, T H

1991-01-01

The metabolism of boldenone (17 beta-hydroxy-1,4-androstem-3-one) in man has been investigated by gas chromatography/mass spectrometry. After oral administration of a 20 mg dose to man, six metabolites were detected in the conjugated fraction of the urinary samples. Boldenone, the major compound excreted in urine, was detected within 34 h after administration. In addition, several metabolites, resulting from the hydroxylation of boldenone and the reduction of the unsaturated carbon bonds of boldenone, were detected in the urine samples varying from 9 to 83 h. Extraction and fractionation of these metabolites were achieved by using XAD-2 column and gas chromatography. The recovery of the whole procedure was studied. Furthermore, the mass spectra of the metabolites are presented and major fragment pathways are discussed.

Nandrolone excretion in sedentary vs physically trained young women.

PubMed

Enea, C; Boisseau, N; Bayle, M L; Flament, M M; Grenier-Loustalot, M F; Denjean, A; Diaz, V; Dugué, B

2010-02-01

We investigated the effects of the menstrual cycle, oral contraception and physical training on exhaustive exercise-induced changes in the excretion of nandrolone metabolites [19-norandrosterone (19-NA), and 19-noretiocholanolone (19-NE)] in young women. Twenty-eight women were allocated to an untrained group (n=16) or a trained group (n=12), depending on their physical training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-), while the trained group was entirely composed of OC+ subjects. Three laboratory sessions were conducted in a randomized order: a prolonged exercise test, a short-term exercise test and a control session. Urine specimens were collected before and 30, 60 and 90 min after the exercise test and at the same times of the day during the control session. Urinary concentrations of nandrolone metabolites were determined by gas chromatography coupled to mass spectrometry. Urinary concentrations of 19-NA and 19-NE ranged from undetectable levels to 1.14 and 0.47 ng/mL, respectively. Nandrolone excretion was not affected by the menstrual cycle phase (early follicular vs mid-luteal), prior physical training, oral contraception or acute physical exercise. Therefore, a urinary concentration of 2 ng/mL of 19-NA appears to be fair as the upper acceptable limit in doping control tests for female athletes.

Excretion of common neutral steroids in healthy subjects as estimated by multi-column chromatography.

PubMed

Vestergaard, P

1978-01-01

Excretion data for common neutral urinary steroids from a total of 330 healthy subjects from different parts of the world and of different sex and age are given. The estimations, which have been performed by multi-column liquid chromatography, include 24 h excretion values for both common 17-oxosteroids and the common metabolites of cortisol, including the cortolones and the cortols. Comparisons are made with values from the world literature and with isotope experiments.

Metabolism of. cap alpha. -C/sup 14/-histidine in the intact rat. II. Radioactive excretion products in urine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolf, G.; Wu, P.H.L.; Heck, W.W.

1956-09-01

The normal metabolic pathways in the intact rat was investigated via the radioactive urinary excretion products following administration of a physiological dose of a radioactive compound such as ..cap alpha..-C/sup 14/-DL-histidine. The major metabolites, except one, excreted in the urine 5 hours after administration of ..cap alpha..-C/sup 14/-DL-histidine were isolated and identified. Glutamic acid and urocanic acids had simlar and low activities, whereas carboxyl-labeled imidazoacetic acid was found to be the principal metabolite with a high level of activity. It was concluded that the main end-product of the catabolism of DL-histidine is imidazoleacetic acid probably formed through imidazolepyruvic acid.

Urinary excretion of mutagens in coke oven workers.

PubMed

Clonfero, E; Granella, M; Marchioro, M; Barra, E L; Nardini, B; Ferri, G; Foà, V

1995-03-01

The influence of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) on urinary mutagenic activity was assessed in 75 coke oven workers, using a highly sensitive bacterial mutagen technique (extraction with C18 resin and liquid micro-preincubation test on strain TA98 of Salmonella typhimurium in the presence of metabolizing and deconjugating enzymes). Exposure to PAHs was assessed according to the urinary excretion of 1-pyrenol; the main confounding factors were checked by the number of cigarettes smoked per day and the levels of nicotine and its metabolites in urine, or by ascertaining whether recommended dietary restrictions had been followed. Of the 20 urine samples which turned out to be positive (producing at least double the number of spontaneous revertants), 19 (95%) belonged to smokers. Only one non-smoker had obvious urinary mutagenic activity, and was highly exposed occupationally to PAHs (urinary 1-pyrenol of 3.930 mumol/mol of creatinine). Of the five urine samples from subjects who had not followed the recommended diet, two (40%) were clearly mutagenic. Multiple regression analysis (n = 67) showed that the presence of samples positive for urinary mutagenic activity depended only on smoking habits, if this confounding factor was assessed according to the number of cigarettes smoked per day, while the significant influence of exposure to PAH could be shown when the confounding factor was objectively estimated according to the urinary levels of nicotine and its metabolites. Assessment of the mutagenic potency of urinary extracts (net revertants/mmol creatinine) confirmed the strong influence of smoking habits on urinary mutagenic activity (all smokers 2156 +/- 2691 versus non-smokers 939 +/- 947 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). In smokers highly exposed to PAHs, greater excretion of mutagens with respect to low-exposure smokers was revealed (3548 +/- 4009 versus 1552 +/- 1227 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). Multiple regression analysis showed that the mutagenic potency of urinary extracts of coke oven workers depended on exposure to PAHs, tobacco smoking habits, and consumption of fried, grilled or barbecued meat. Increased urinary mutagenic activity strengthens epidemiological evidence of the increased risk of renal and urinary tract tumours in these workers. The presence of mutagenic metabolites in urine as a result of occupational exposure to PAH may be demonstrated only by using highly sensitive techniques for assessing urinary mutagenic activity in studies which include careful checking of the main confounding factors.

The metabolism of 2-trifluormethylaniline and its acetanilide in the rat by 19F NMR monitored enzyme hydrolysis and 1H/19F HPLC-NMR spectroscopy.

PubMed

Tugnait, M; Lenz, E M; Hofmann, M; Spraul, M; Wilson, I D; Lindon, J C; Nicholson, J K

2003-01-01

The urinary excretion profile and identity of the metabolites of 2-trifluoromethyl aniline (2-TFMA) and 2-trifluoromethyl acetanilide (2-TFMAc), following i.p. administration to the rat at 50 mg kg(-1), were determined using a combination of 19F NMR monitored enzyme hydrolysis, SPEC-MS and 19F/1H HPLC-NMR. A total recovery of approximately 96.4% of the dose was excreted into the urine as seven metabolites. The major routes of metabolism were N-conjugation (glucuronidation), and ring-hydroxylation followed by sulphation (and to a lesser extent glucuronidation). The major metabolites excreted into the urine for both compounds were a labile N-conjugated metabolite (a postulated N-glucuronide) and a sulphated ring-hydroxylated metabolite (a postulated 4-amino-5-trifluoromethylphenyl sulphate) following dosing of 2-TFMA. These accounted for approximately 53.0 and 31.5% of the dose, respectively. This study identifies problems on sample component instability in the preparation and analysis procedures.

Stereometabolism of ethylbenzene in man: gas chromatographic determination of urinary excreted mandelic acid enantiomers and phenylglyoxylic acid and their relation to the height of occupational exposure.

PubMed

Korn, M; Gfrörer, W; Herz, R; Wodarz, I; Wodarz, R

1992-01-01

Ethylbenzene is an important industrial solvent and a key substance in styrene production. Ethylbenzene metabolism leads to the formation of mandelic acid, which occurs in two enantiomeric forms, and phenylglyoxylic acid. To decide which enantiomer is preferably formed, 70 urine samples of exposed workers were taken at the end of shifts and--after 3-pentyl ester derivatisation--gas chromatographically analysed. The R/S ratio of mandelic acid enantiomers in urine amounts to 19:1, which means that R-mandelic acid is a major metabolite and S-mandelic acid is one of the minor urinary metabolites of ethylbenzene in man. The R/S ratio is independent of ambient air concentration of ethylbenzene within the investigated range. Compared to an ethylbenzene monoexposure the height of total mandelic acid excretion is decreased in the case of coexposure to other aromatic solvents.

Urinary Excretion of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide, and Norbuprenorphine-Glucuronide in Pregnant Women Receiving Buprenorphine Maintenance Treatment

PubMed Central

Kacinko, Sherri L.; Jones, Hendree E.; Johnson, Rolley E.; Choo, Robin E.; Concheiro-Guisan, Marta; Huestis, Marilyn A.

2011-01-01

BACKGROUND Buprenorphine (BUP) is under investigation as a medication therapy for opioid-dependent pregnant women. We investigated BUP and metabolite disposition in urine from women maintained on BUP during the second and third trimesters of pregnancy and postpartum. METHODS We measured BUP, norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and NBUP-Gluc concentrations in 515 urine specimens collected thrice weekly from 9 women during pregnancy and postpartum. Specimens were analyzed using a fully validated liquid chromatography-mass spectrometry method with limits of quantification of 5 µg/L for BUP and BUP-Gluc and 25 µg/L for NBUP and its conjugated metabolite. We examined ratios of metabolites across trimesters and postpartum to identify possible changes in metabolism during pregnancy. RESULTS NBUP-Gluc was the primary metabolite identified in urine and exceeded BUP-Gluc concentrations in 99% of specimens. Whereas BUP-Gluc was identified in more specimens than NBUP, NBUP exceeded BUP-Gluc concentrations in 77.9% of specimens that contained both analytes. Among all participants, the mean BUP-Gluc:NBUP-Gluc ratio was significantly higher in the second trimester compared to the third trimester, and there were significant intrasubject differences between trimesters in 71% of participants. In 3 women, the percent daily dose excreted was higher during pregnancy than postpregnancy, consistent with other data indicating increased renal elimination of drugs during pregnancy. CONCLUSIONS These data are the first to evaluate urinary disposition of BUP and metabolites in a cohort of pregnant women. Variable BUP excretion during pregnancy may indicate metabolic changes requiring dose adjustment during later stages of gestation. PMID:19325013

Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model.

PubMed

Jongeneelen, Frans; ten Berge, Wil

2012-08-01

A physiologically based toxicokinetic (PBTK) model can predict blood and urine concentrations, given a certain exposure scenario of inhalation, dermal and/or oral exposure. The recently developed PBTK-model IndusChemFate is a unified model that mimics the uptake, distribution, metabolism and elimination of a chemical in a reference human of 70 kg. Prediction of the uptake by inhalation is governed by pulmonary exchange to blood. Oral uptake is simulated as a bolus dose that is taken up at a first-order rate. Dermal uptake is estimated by the use of a novel dermal physiologically based module that considers dermal deposition rate and duration of deposition. Moreover, evaporation during skin contact is fully accounted for and related to the volatility of the substance. Partitioning of the chemical and metabolite(s) over blood and tissues is estimated by a Quantitative Structure-Property Relationship (QSPR) algorithm. The aim of this study was to test the generic PBTK-model by comparing measured urinary levels of 1-hydroxypyrene in various inhalation and dermal exposure scenarios with the result of model simulations. In the last three decades, numerous biomonitoring studies of PAH-exposed humans were published that used the bioindicator 1-hydroxypyrene (1-OH-pyrene) in urine. Longitudinal studies that encompass both dosimetry and biomonitoring with repeated sampling in time were selected to test the accuracy of the PBTK-model by comparing the reported concentrations of 1-OHP in urine with the model-predicted values. Two controlled human volunteer studies and three field studies of workers exposed to polycyclic aromatic hydrocarbons (PAH) were included. The urinary pyrene-metabolite levels of a controlled human inhalation study, a transdermal uptake study of bitumen fume, efficacy of respirator use in electrode paste workers, cokery workers in shale oil industry and a longitudinal study of five coke liquefaction workers were compared to the PBTK-predicted values. The simulations showed that the model-predicted concentrations of urinary pyrene and metabolites over time, as well as peak-concentrations and total excreted amount in different exposure scenarios of inhalation and transdermal exposure were in all comparisons within an order of magnitude. The model predicts that only a very small fraction is excreted in urine as parent pyrene and as free 1-OH-pyrene. The predominant urinary metabolite is 1-OH-pyrene-glucuronide. Enterohepatic circulation of 1-OH-pyrene-glucuronide seems the reason of the delayed release from the body. It appeared that urinary excretion of pyrene and pyrene-metabolites in humans is predictable with the PBTK-model. The model outcomes have a satisfying accuracy for early testing, in so-called 1st tier simulations and in range finding. This newly developed generic PBTK-model IndusChemFate is a tool that can be used to do early explorations of the significance of uptake of pyrene in the human body following industrial or environmental exposure scenarios. And it can be used to optimize the sampling time and urine sampling frequency of a biomonitoring program.

Absorption, Distribution, Metabolism, and Excretion of the Androgen Receptor Inhibitor Enzalutamide in Rats and Dogs.

PubMed

Ohtsu, Yoshiaki; Gibbons, Jacqueline A; Suzuki, Katsuhiro; Fitzsimmons, Michael E; Nozawa, Kohei; Arai, Hiroshi

2017-08-01

Enzalutamide is an androgen receptor inhibitor that has been approved in several countries. Absorption, distribution, metabolism, and excretion (ADME) data in animals would facilitate understanding of the efficacy and safety profiles of enzalutamide, but little information has been reported in public. The purpose of this study was to clarify the missing ADME profile in animals. ADME of 14 C-enzalutamide after oral administration as Labrasol solution were investigated in non-fasted male Sprague-Dawley rats and beagle dogs. Plasma concentrations of 14 C-enzalutamide peaked in rats and dogs at 6-8 h after a single oral administration. In most tissues, radioactivity concentration peaked at 4 h after administration. Excluding the gastrointestinal tract, tissues with the highest concentration of radioactivity were liver, fat, and adrenal glands. The tissue concentrations of radioactivity declined below the limit of quantitation or <0.89 % of maximum concentration by 168 h post-dose. Two known metabolites (M1 and M2) and at least 15 novel possible metabolites were detected in this study. M1 was the most abundant metabolite in both rats and dogs. Unchanged drug was a minor component in excreta. In intact rats, the mean urinary and fecal excretion of radioactivity accounted for 44.20 and 49.80 % of administered radioactivity, respectively. In intact dogs, mean urinary and fecal excretion was 62.00 and 22.30 % of the administered radioactivity, respectively. Rapid oral absorption was observed in rats and dogs when 14 C-enzalutamide was administered as Labrasol solution. Tissue distribution in rats was clarified. The elimination of enzalutamide is mediated primarily by metabolism. Species differences were observed in excretion route.

Effect of two oral contraceptives with different ethinyl estradiol and levonorgestrel concentrations on the urinary excretion of biochemical vasoactive markers.

PubMed

Mueck, A O; Seeger, H; Petersen, G; Schulte-Wintrop, E; Wallwiener, D

2001-12-01

In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic peptide formed in the kidney, were measured as markers. In a comparative, double-blind, randomized, parallel group study, 34 women received Leios and 33 women Stediril 30. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged for both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, crucial for the resulting effect on vascular tone, increased significantly. For the serotonin metabolite, no changes were observed for both contraceptives. The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values. These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers, at least after 12 cycles of treatment. The positive influence of these contraceptives on the various markers investigated may improve vascular tone, impede development of atherosclerosis and arterial thrombosis, and improve water and electrolyte homeostasis. These effects most likely can be attributed to the estrogenic component. Levonorgestrel may elicit no impact on these estrogen-induced changes that, however, seem only to be manifested after a longer treatment period.

α-Tocopherol does not accelerate depletion of γ-tocopherol and tocotrienol or excretion of their metabolites in rats.

PubMed

Uchida, Tomono; Nomura, Saki; Sakuma, Eri; Hanzawa, Fumiaki; Ikeda, Saiko

2013-07-01

From an enzyme kinetic study using rat liver microsomes, α-tocopherol has been suggested to accelerate the other vitamin E catabolism by stimulating vitamin E ω-hydroxylation, the late limiting reaction of the vitamin E catabolic pathway. To test the effect of α-tocopherol on catabolism of the other vitamin E isoforms in vivo, we determined whether α-tocopherol accelerates depletion of γ-tocopherol and tocotrienol and excretion of their metabolites in rats. Male Wistar rats were fed a γ-tocopherol-rich diet for 6 weeks followed by a γ-tocopherol-free diet with or without α-tocopherol for 7 days. Intake of γ-tocopherol-free diets lowered γ-tocopherol concentrations in serum, liver, adrenal gland, small intestine, and heart, but there was no effect of dietary α-tocopherol on γ-tocopherol concentrations. The level of urinary excretion of γ-tocopherol metabolite was not affected by dietary α-tocopherol. Next, the effect of α-tocopherol on tocotrienol depletion was examined using rats fed a tocotrienol-rich diet for 6 weeks. Subsequent intake of a tocotrienol-free diet with or without α-tocopherol for 7 days depleted concentrations of α- and γ-tocotrienol in serum and tissues, which was accompanied by a decrease in the excretion of γ-tocotrienol metabolite. However, neither the tocotrienol concentration nor γ-tocotrienol metabolite excretion was affected by dietary α-tocopherol. These data showed that dietary α-tocopherol did not accelerate the depletion of γ-tocopherol and tocotrienol and their metabolite excretions, suggesting that the positive effect of α-tocopherol on vitamin E ω-hydroxylase is not sufficient to affect the other isoform concentrations in tissues.

[13C]Nandrolone excretion in trained athletes: interindividual variability in metabolism.

PubMed

Baume, Norbert; Avois, Lidia; Schweizer, Carine; Cardis, Christine; Dvorak, Jiri; Cauderay, Michel; Mangin, Patrice; Saugy, Martial

2004-02-01

Nandrolone is one of the most abused anabolic steroids, and its use in doping is increasing, as revealed by numerous positive cases during recent years in various sports. Different authors have reported the possible natural production of nandrolone metabolites in humans, and some of these authors argued that exhaustive exercise could increase nandrolone production in the body or induce dehydration and consequently lead to an increase of nandrolone metabolites in urine. Volunteers (n = 22) ingested two 25-mg doses of [(13)C]nandrolone at 24-h intervals and collected urine specimens for 5 days. The labeled nandrolone metabolites 19-norandrosterone and 19-noretiocholanolone were identified and quantified by gas chromatography-mass spectrometry. Interindividual variability was observed in nandrolone excretion patterns and kinetics, as well as for the noretiocholanolone:norandrosterone ratio. The amounts of nandrolone metabolites measured at the excretion peak varied between 1180 and 38 661 microg/L for norandrosterone and 576 and 12 328 microg/L for noretiocholanolone. At the end of the excretion period, the noretiocholanolone:norandrosterone ratio was sometimes >1. The analysis of numerous spot-urine samples allowed the determination of an acceptable correlation between urinary creatinine and specific gravity for placebo- and steroid-treated individuals: y = 0.0052ln(x) + 1.0178 (r(2) = 0.8142) and y = 0.0068ln(x) + 1.0172 (r(2) = 0.7730), respectively. The excretion kinetics and patterns of labeled nandrolone show interindividual variability. More investigations are currently underway to estimate the influence of exhaustive exercises on excretion of labeled nandrolone metabolites in urine.

Uptake of pyrene in a breast-fed child of a mother treated with coal tar.

PubMed

Scheepers, Paul T J; van Houtum, Jeanette L M; Anzion, Rob B M; Harder, Rianne; Bos, Rob P; van der Valk, Pieter G M

2009-01-01

A woman was treated for atopic dermatitis with coal tar containing ointments. Coal tar containing ointments contain genotoxic polycyclic aromatic hydrocarbons. Over a period of 50 days the accumulated dose of different coal tar containing ointments treatments corresponded to 993 mg of pyrene and 464 mg of benz[a]pyrene. During this treatment she gave breast milk to her 3-month-old daughter. Analysis of urine samples from the breast-fed child showed elevated levels of urinary excretion of a metabolite of pyrene (1-hydroxypyrene, 1-OHP). These levels were in the same range as urinary excretion levels of this metabolite observed in the mother's urine. As no pyrene was observed in breast milk at a limit of determination of 0.0035 micromol/L, transfer of pyrene from mother to child via breast milk is not likely. Also, a low level of 1-hydroxypyrene observed in the mother's milk did not account for the observed urinary excretion levels in the child. It must therefore be assumed that pyrene was transferred from mother to child via another route, presumably direct skin-to-skin or skin-to-mouth contact. Dermatologists should inform their patients who receive treatment with coal tar containing ointments of the risk of transfer of polycyclic aromatic hydrocarbons by skin-to-skin or skin-to-mouth contact.

Dietary exposure to 5-hydroxymethylfurfural from Norwegian food and correlations with urine metabolites of short-term exposure.

PubMed

Husøy, T; Haugen, M; Murkovic, M; Jöbstl, D; Stølen, L H; Bjellaas, T; Rønningborg, C; Glatt, H; Alexander, J

2008-12-01

5-Hydroxymethylfurfural (HMF) is formed in carbohydrate-rich food during acid-catalysed dehydration and in the Maillard reaction from reducing sugars. HMF is found in mg quantities per kg in various foods. HMF is mainly metabolised to 5-hydroxymethyl-2-furoic acid (HMFA), but unknown quantities of the mutagenic 5-sulphoxymethylfurfural (SMF) may also be formed, making HMF potentially hazardous to humans. We determined the HMF content in Norwegian food items and estimated the dietary intake of HMF in 53 volunteers by means of 24h dietary recall. The estimated intakes of HMF were correlated with urinary excretion of HMFA. Coffee, prunes, dark beer, canned peaches and raisins had the highest levels of HMF. The 95th percentile of the estimated daily dietary intake of HMF and the 24h urinary excretion of HMFA were 27.6 and 28.6mg, respectively. Coffee, dried fruit, honey and alcohol were identified as independent determinants of urinary HMFA excretion. Most participants had lower estimated HMF intake than the amount of HMFA excreted in urine. In spite of this there was a significant correlation (r=0.57, P<0.001) between the estimated HMF intake and urinary HMFA. Further studies are needed to reveal alternative sources for HMF exposure.

Urinary excretion of heptanones, heptanoles and 2,5-heptanedione after controlled acute exposure of volunteers to n-heptane.

PubMed

Rossbach, Bernd; Kegel, Peter; Letzel, Stephan

2018-03-27

A lack of well-established parameters and assessment values currently impairs biomonitoring of n-heptane exposure. Using controlled inhalation experiments, we collected information on urinary n-heptane metabolite concentrations and the time course of metabolite excretion. Relationships between external and internal exposure were analysed to investigate the suitability of selected metabolites to reflect n-heptane uptake. Twenty healthy, non-smoking males (aged 19-38 years, median 25.5) were exposed for 3 h to 167, 333 and 500 ppm n-heptane, each. Spot urine samples of the volunteers, collected before exposure and during the following 24 h, were analysed for heptane-2-one, 3-one, 4-one, 2,5-dione, 1-ol, 2-ol, 3-ol, and 4-ol using headspace solid phase dynamic extraction gas chromatography/mass spectrometry (HS-SPDE-GC/MS). Starting from median pre-exposure concentrations between <0.5 (3-one) and 82.9 μg/L (4-one), exposure increased the concentrations for all parameters except for 4-one. Median post-exposure concentrations ranged up to 840.4 μg/L (2-ol) and decreased with half-lifes <3 h after exposure. Non-parametric correlation analyses (n = 47, p < 0.05) revealed weak to moderate associations of volume related metabolite excretion with external exposure for 2-one, 3-one and 2,5-dione (R = 0.332-0.753). Heptanol excretion was moderately associated with exposure (R ≥ 0.509) only after creatinine adjustment. Lacking association with external exposure impedes the use of 4-one as heptane biomarker, whereas 2-ol and 3-ol turned out to be sensitive indicators of exposure if creatinine correction is applied. By providing fundamental data on a panel of eight potential heptane metabolites, our study can help to promote biological monitoring of n-heptane exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

Pregnancy and Lactation Alter Biomarkers of Biotin Metabolism in Women Consuming a Controlled Diet123

PubMed Central

Perry, Cydne A; West, Allyson A; Gayle, Antoinette; Lucas, Lauren K; Yan, Jian; Jiang, Xinyin; Malysheva, Olga; Caudill, Marie A

2014-01-01

Background: Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 μg/d, whereas 35 μg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. Objective: The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. Methods: To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 μg of dietary biotin/d as part of a mixed diet. Results: Over the course of the study, pregnant women excreted 69% more (vs. control; P < 0.001) 3-hydroxyisovaleric acid (3-HIA), a metabolite that accumulates during the catabolism of leucine when the activity of biotin-dependent methylcrotonyl–coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3-hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. Conclusions: Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and suggest that biotin intakes exceeding current recommendations are needed to meet the demands of these reproductive states. This trial was registered at clinicaltrials.gov as NCT01127022. PMID:25122647

Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler

PubMed Central

Hindle, M.; Peers, E. M.; Parry-Billings, M.; Chrystyn, H.

1997-01-01

Aims The number of dry powder inhaler (DPI) devices could increase because they are easier to use than a metered dose inhaler (MDI). Using urinary excretion, the relative bioavailability of salbutamol to the lungs and the body for a prototype DPI has been compared with an MDI. Methods A randomized, double-blind, two way crossover study compared the amount of salbutamol in the urine 30 min following inhalation of 2×100 μg salbutamol from a prototype DPI (Innovata Biomed Ltd, UK) and a Ventolin® (Allen and Hanburys Ltd, UK) MDI in 10 volunteers. The amount of salbutamol and its metabolite, the ester sulphate conjugate, renally excreted up to 24 h post inhalation was also determined to evaluate the relative bioavailability of salbutamol to the body. Results The mean (s.d.) 30 min post-treatment urinary excretion for the prototype DPI and MDI was 8.4 (2.6) and 5.0 (1.9) μg, respectively (P<0.001). The total amount of salbutamol and its ester metabolite excreted in the urine over the 24 h period after inhalation was 187.9 (77.6) and 137.6 (40.0) μg (P<0.05). Conclusions The prototype DPI delivered more salbutamol to the body and the lungs than a conventional MDI. This finding supports further development of the prototype DPI. The urinary salbutamol method is able to discriminate between two different inhalation systems. PMID:9088593

Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.

PubMed Central

Ferry, N; Geoffroy, J; Pozet, N; Cuisinaud, G; Benzoni, D; Zech, P Y; Sassard, J

1988-01-01

1. The kinetics of a single oral dose (300 mg) of cicletanine a new antihypertensive drug with diuretic properties, and its effects on the urinary excretion of electrolytes and of the major stable metabolites of prostacyclin and thromboxane A2 were studied in patients with normal renal function (n = 6), mild (n = 9) and severe (n = 10) renal insufficiency. 2. In normotensive subjects with normal renal function, cicletanine was rapidly and regularly absorbed, its apparent elimination half-life established around 7 h, and both its renal clearance (0.4 ml min-1) and its cumulative renal excretion (0.85% of the administered dose), were low. Mild renal insufficiency did not significantly alter these parameters, while severe renal impairment reduced the renal clearance and the cumulative urinary excretion of cicletanine and increased its apparent elimination half-life (31 h). However the area under the plasma curve was not changed due to reduced plasma concentrations in these patients. 3. Cicletanine induced a rapid and marked (four fold as a mean) increase in the urinary excretion of water, sodium and potassium which lasted for 6 to 10 h, in subjects with normal renal function. Renal insufficiency did not alter the slope of the calculated plasma concentration-effects curves but reduced the maximum effect observed for water, sodium and potassium. 4. A single oral dose of cicletanine did not change the urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in the three groups of patients studied, the basal values of which being found to be closely related to the creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3358898

Pantothenic acid deficiency may increase the urinary excretion of 2-oxo acids and nicotinamide catabolites in rats.

PubMed

Shibata, Katsumi; Inomoto, Kasumi; Nakata, Chifumi; Fukuwatari, Tsutomu

2013-01-01

Pantothenic acid (PaA) is involved in the metabolism of amino acids as well as fatty acid. We investigated the systemic metabolism of amino acids in PaA-deficient rats. For this purpose, urine samples were collected and 2-oxo acids and L-tryptophan (L-Trp) and its metabolites including nicotinamide were measured. Group 1 was freely fed a conventional chemically-defined complete diet and used as an ad lib-fed control, which group was used for showing reference values. Group 2 was freely fed the complete diet without PaA (PaA-free diet) and used as a PaA-deficient group. Group 3 was fed the complete diet, but the daily food amount was equal to the amount of the PaA-deficient group and used as a pair-fed control group. All rats were orally administered 100 mg of L-Trp/kg body weight at 09:00 on day 34 of the experiment and the following 24-h urine samples were collected. The urinary excretion of the sum of pyruvic acid and oxaloacetic acid was higher in rats fed the PaA-free diets than in the rats fed pair-fed the complete diet. PaA deficiency elicited the increased urinary excretion of anthranilic acid and kynurenic acid, while the urinary excretion of xanthurenic acid decreased. The urinary excretion of L-Trp itself, 3-hydroxyanthranilic acid, and quinolinic acid revealed no differences between the rats fed the PaA-free and pair-fed the complete diets. PaA deficiency elicited the increased excretion of N(1)-methylnicotinamide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide. These findings suggest that PaA deficiency disturbs the amino acid catabolism.

Urinary androgens and cortisol metabolites in field-sampled bonobos (Pan paniscus).

PubMed

Dittami, John; Katina, Stanislav; Möstl, Erich; Eriksson, Jonas; Machatschke, Ivo H; Hohmann, Gottfried

2008-02-01

Urinary metabolites of androgens and cortisol were measured in free-living male and female bonobos. Sex differences and correlations between adrenal and gonadal steroid excretion were investigated. The immunoreactive concentrations of androgens were measured with two different androgen assays. One assay used a testosterone (T) antibody raised with a 17beta-hydroxy group, and the other employed an antibody raised against a reduced form, 5alpha-androstane-17alpha-ol-3-one-CM (17alpha) with cross reactivity for epitestosterone and 5alpha-androstanedione. Both assays have been used in bonobo and chimpanzee studies where non-invasive techniques were employed. The levels of 17alpha-androgen metabolites were 1.7- and 3-fold higher than those of T-metabolites in males and females. The two androgen assay results correlated in males but not females. There was a sex difference in the T-metabolites measured. Male levels were significantly higher. Levels of 17alpha in the two sexes were similar. Cortisol metabolite levels (CORT) were similar between the sexes. The T-metabolites were significantly correlated with CORT in males but not in females. In females, the 17alpha-androgen metabolites correlated with CORT. This suggests that either androgen secretion or metabolism differs between the sexes. A parsimonious interpretation of the androgen assay cortisol/androgen correlation differences would be that larger components of dehydroepiandrosterone (DHEA), androstenedione or epitestosterone from the adrenal androgens were being excreted and measured in the females. The CORT/T metabolite interactions in males may reflect male-specific social or metabolic endocrine conditions.

Effects of drugs which influence renal transport systems on the urinary excretion of the beta 2-adrenoceptor agonist clenbuterol and the anabolic steroids ethinylestradiol and methyltestosterone.

PubMed

Gleixner, A; Sauerwein, H; Meyer, H H

1997-01-01

The aim of this study was to determine whether the illegal application of clenbuterol, ethinylestradiol and methyltestosterone in cattle as growth promoters can be concealed by co-treatment with drugs that affect urinary excretion. Six male veal calves were fed with 0.8 micrograms clenbuterol kg-1 of body weight (BW), 3.5 micrograms ethinylestradiol kg-1 BW and 35 micrograms methyltestosterone kg-1 BW together twice daily for 28 days. At the eighth day of clenbuterol, ethinylestradiol and methyltestosterone treatment each calf was additionally fed either with probenecid, para-aminohippuric acid, trimethoprim, famotidine or cimetidine at three different doses which were increased in weekly intervals. During the treatment 24 h-urine and blood samples (once daily) were obtained and analysed for clenbuterol, ethinylestradiol and methyltestosterone by specific enzyme immunoassay. By high performance liquid chromatography/enzyme immunoassay it was determined whether these drugs or their metabolites interfered with the immunological detection of the growth promoters. Clenbuterol, ethinylestradiol and methyltestosterone could be detected in plasma and urine throughout the whole experiment. Co-treatment with probenecid led to a five-fold reduction in urinary excretion of ethinylestradiol and co-treatment with trimethoprim led to a three-fold reduction in urinary excretion of clenbuterol. None of the drugs reduced urinary excretion of the growth promoters to concentrations below the limit of detection. The detection of these three growth promoters in urine samples from calves which were co-treated with the drugs tested in this study can thus not be prevented.

[Disorder of porphyrin metabolism in thallium intoxication (author's transl)].

PubMed

Graben, N; Doss, M; Klöppel, H A

1978-08-04

A 19-year old male ingested in suicidal attempt 750 mg of thallium. He developed the characteristic symptoms of thallium intoxication. During the acute phase the urinary excretion of porphyrins and porphyrin precursors was largely increased. The percentage distribution of the individual metabolites of heme synthesis revealed a preponderance of kopro- and uroporphyrin. This constellation (kopro- greater than uro- greater than tricarboxylic porphyrin) differs appreciably from that one in lead intoxication. The observation of increased urinary excretion of porphyrins and their precursors in a possibly particular spectrum in thallium intoxication is of special interest for differential-diagnostic reasoning. In each case of a toxic disorder of porphyrin metabolism thallium intoxication ought to be considered a possible cause.

Effects of harmane on growth and in vivo metabolism of aflatoxin B1 in male and female rats.

PubMed

Billaud, C

1991-01-01

The role of harmane, a beta-carboline formed during pyrolysis of tryptophan, on the metabolism of AFB1, growth and some parameters of the nutritional status was investigated in the rat. Male and female Wistar rats were fed a semi-synthetic diet containing AFB1 (2 ppm), harmane (250 ppm) or both compounds, for 33 days after weaning. Qualitative and quantitative differences in the urinary and faecal excretion of parental compound and metabolites were assessed by HPLC analysis. Harmane did not modify appreciably the growth and the other nutritional parameters studied. Similar excretion patterns of AFB1 metabolites were observed in males and females. Harmane caused a limited increase in the excretion of AFM1 in faeces but not in urine, without altering the growth process in rats of either sex.

Intra- and inter-individual variations of blood and urinary water-soluble vitamins in Japanese young adults consuming a semi-purified diet for 7 days.

PubMed

Shibata, Katsumi; Fukuwatari, Tsutomu; Watanabe, Toshiaki; Nishimuta, Mamoru

2009-12-01

We have previously reported the levels of water-soluble vitamins in the blood and urine of Japanese young adults. In the present paper, to assess the variations in these water-soluble vitamin markers during the above experiment, we comprehensively determined the intra- and inter-individual variations of blood and urinary water-soluble vitamins to exactly the same amount of water-soluble vitamin intakes in the same experiment. The blood samples before breakfast and the 24-h urine samples were periodically collected from Japanese college male (n=10) and female (n=10) students consuming a semi-purified diet with water-soluble vitamins based on Japanese Dietary Reference Intakes for 7 d, and the intra- and inter-individual variations of blood and urinary water-soluble vitamins or their metabolites in blood and urine samples after adaptation were calculated. Although urinary excretion of vitamin B(12) and vitamin C showed high intra-individual variations in both males and females, other urinary vitamins and all blood vitamins showed less than 20% of within-subject coefficients of variance in either male or female. Those showing more than 20% of between-subject coefficients of variances in both male and female were blood vitamin B(6), vitamin B(12) and folate levels, and urinary vitamin B(1), vitamin B(2), vitamin B(12), nicotinamide metabolites, pantothenic acid, biotin and vitamin C. These results showed that oral administration of constant of water-soluble vitamins generally decreased intra-individual variation, while individual differences in urinary vitamin excretion were observed.

Urinary water-soluble vitamins and their metabolite contents as nutritional markers for evaluating vitamin intakes in young Japanese women.

PubMed

Fukuwatari, Tsutomu; Shibata, Katsumi

2008-06-01

Little information is available to estimate water-soluble vitamin intakes from urinary vitamins and their metabolite contents as possible nutritional markers. Determination of the relationships between the oral dose and urinary excretion of water-soluble vitamins in human subjects contributes to finding valid nutrition markers of water-soluble vitamin intakes. Six female Japanese college students were given a standard Japanese diet in the first week, the same diet with a synthesized water-soluble vitamin mixture as a diet with approximately onefold vitamin mixture based on Dietary Reference Intakes (DRIs) for Japanese in the second week, with a threefold vitamin mixture in the third week, and a sixfold mixture in the fourth week. Water-soluble vitamins and their metabolites were measured in the 24-h urine collected each week. All urinary vitamins and their metabolite levels except vitamin B(12) increased linearly in a dose-dependent manner, and highly correlated with vitamin intake (r=0.959 for vitamin B(1), r=0.927 for vitamin B(2), r=0.965 for vitamin B(6), r=0.957 for niacin, r=0.934 for pantothenic acid, r=0.907 for folic acid, r=0.962 for biotin, and r=0.952 for vitamin C). These results suggest that measuring urinary water-soluble vitamins and their metabolite levels can be used as good nutritional markers for assessing vitamin intakes.

Metabonomics approach to determine metabolic differences between green tea and black tea consumption.

PubMed

Van Dorsten, Ferdi A; Daykin, Clare A; Mulder, Theo P J; Van Duynhoven, John P M

2006-09-06

The purpose of this study was to compare the effects of black and green tea consumption on human metabolism. Seventeen healthy male volunteers consumed black tea, green tea, or caffeine in a randomized crossover study. Twenty-four-hour urine and blood plasma samples were analyzed by NMR-based metabonomics, that is, high-resolution 1H NMR metabolic profiling combined with multivariate statistics. Green and black tea consumption resulted in similar increases in urinary excretion of hippuric acid and 1,3-dihydroxyphenyl-2-O-sulfate, both of which are end products of tea flavonoid degradation by colonic bacteria. Several unidentified aromatic metabolites were detected in urine specifically after green tea intake. Interestingly, green and black tea intake also had a different impact on endogenous metabolites in urine and plasma. Green tea intake caused a stronger increase in urinary excretion of several citric acid cycle intermediates, which suggests an effect of green tea flavanols on human oxidative energy metabolism and/or biosynthetic pathways.

Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation.

PubMed

Reznik, Y; Dehennin, L; Coffin, C; Mahoudeau, J; Leymarie, P

2001-01-01

19-Nortestosterone (nandrolone) is an anabolic steroid compound widely used as a doping agent by athletes. The analysis of its urinary metabolites, 19-norandrosterone (NA) and 19-noretiocholanolone (NE) glucuronides, allows the detection of surreptitious administration of nandrolone in sport. A threshold concentration at 2 microgram/L urinary nandrolone metabolites is advocated by the International Olympic Committee for the detection of doping, but some controversy concerning the validity of this threshold arose from the demonstration of endogenous production of nandrolone in mammals, including humans. The regulation of human nandrolone production and its contribution in vivo to the process of aromatization remain unknown. In the present study 10 healthy men were successively submitted to insulinic stress and gonadal stimulation by hCG administration. Urinary NA and NE concentrations were quantified by gas chromatography-mass spectrometry. NA was detected in basal urine samples from all subjects, with a mean urinary excretion rate (UER) of 3.17 +/- 0.35 ng/h, whereas NE was detected in 4 of 10 (UER range, 0.8-4.7 ng/h). Insulinic hypoglycemia did not significantly modify mean NA UER despite random intraindividual variations between timed urine collections. After hCG administration, NA UER increased by 250% (P < 0.01) and estradiol (E(2)) UER by 260% (P < 0.001). The maximum NA concentration obtained after stimulation was 0.43 microgram/L. NA UER, plasma E(2), and E(2)/T ratio peaked on day 1 after hCG administration, whereas plasma T peaked later on day 3. NA UER correlated with plasma E(2) (r = 0.61; P < 0.001) and E(2)/T (r = 0.51; P < 0.001), but not with plasma T. In conclusion, insulinic stress did not significantly alter nandrolone metabolism, whereas the effect of hCG was a stimulation of NA excretion in all subjects, which constitutes strong support for the endogenous origin of low basal NA excretion. The comparative kinetics of NA UER, plasma E(2), and E(2)/T ratio suggest a contribution of the aromatase process to nandrolone biosynthesis in man.

Vitamin D, Hypercalciuria and Kidney Stones

PubMed Central

Letavernier, Emmanuel; Daudon, Michel

2018-01-01

The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption—as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements. PMID:29562593

Metabolism study of boldenone in human urine by gas chromatography-tandem mass spectrometry.

PubMed

Wu, Xinchen; Gao, Feng; Zhang, Wenxin; Ni, Jian

2015-11-10

Boldenone (BOLD), an anabolic steroid, is likely to be abused in livestock breeding and in sports. Although some of BOLD metabolites in human urine, such as 5β-adrost-1-en-17β-ol-3-one (BM1), have been detected, investigations on their excretion patterns for both genders are insufficient. Moreover, little research on 17α-BOLD glucuronide as a metabolite in human urine has been reported. The aim of this study is to make a contribution to the knowledge of 17β-BOLD metabolism in humans. Three male and three female volunteers were orally administrated with 30mg 17β-BOLD. Urine samples were collected and analyzed with gas chromatography-tandem mass spectrometry. The data proved that 17β-BOLD, BM1, and 17α-BOLD were excreted in urine in both free and glucuronic conjugated forms after administration of 17β-BOLD. For most subjects, the urinary concentrations of BM1 were higher than that of 17β-BOLD. 17α-BOLD was excreted in small amounts. 17α-BOLD, 17β-BOLD, and BM1 were present naturally in urine with low concentrations. Administration of 30mg 17β-BOLD could not influence the excretion profiles of urinary androsterone, etiocholanolone, and testosterone/epitestosterone ratio. There were no differences in BOLD metabolic patterns between man and woman. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential antiproliferative activity of polyphenol metabolites against human breast cancer cells and their urine excretion pattern in healthy subjects following acute intake of a polyphenol-rich juice of grumixama (Eugenia brasiliensis Lam.).

PubMed

Teixeira, L L; Costa, G R; Dörr, F A; Ong, T P; Pinto, E; Lajolo, F M; Hassimotto, N M A

2017-06-21

The bioavailability and metabolism of anthocyanins and ellagitannins following acute intake of grumixama fruit, native Brazilian cherry, by humans, and its in vitro antiproliferative activity against breast cancer cells (MDA-MB-231) were investigated. A single dose of grumixama juice was administered to healthy women (n = 10) and polyphenol metabolites were analyzed in urine and plasma samples collected over 24 h. The majority of the metabolites circulating and excreted in urine were phenolic acids and urolithin conjugates, the gut microbiota catabolites of both classes of polyphenols, respectively. According to pharmacokinetic parameters, the subjects were divided into two distinct groups, high and low urinary metabolite excretors. The pool of polyphenol metabolites found in urine samples showed a significant inhibition of cell proliferation and G2/M cell cycle arrest in MDA-MB-231 cells. Our findings demonstrate the large interindividual variability concerning the polyphenol metabolism, which possibly could reflect in health promotion.

Tissue, Dosimetry, Metabolism and Excretion of Pentavalent and Trivalent Dimethylated Arsenic in Mice after Oral Administration

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic inmice after acute oral administration. Adult fema...

The effects of concentrate added to pineapple (Ananas comosus Linn. Mer.) waste silage in differing ratios to form complete diets, on digestion, excretion of urinary purine derivatives and blood metabolites in growing, male, Thai swamp buffaloes.

PubMed

Jetana, T; Suthikrai, W; Usawang, S; Vongpipatana, C; Sophon, S; Liang, J B

2009-04-01

Four, male, growing Thai swamp buffaloes (197 +/- 5.3 kg and all 1 year old) were used to evaluate the effects of concentrate added to pineapple waste silage in differing ratios, to form a complete diet, studying in vivo digestion, the rate of passage, microbial protein synthesis and blood metabolites. Animals were fed ad libitum with 4 diets, using four combinations of pineapple waste silage (P) and concentrate (C), in the proportions (on a dry matter basis) of 0.8:0.2 (P80:C20), 0.6:0.4 (P60:C40), 0.4:0.6 (P40:C60) and 0.2:0.8 (P20:C80). The results showed that the intakes of dry matter (DM), organic matter (OM), nitrogen (N), the N-balance, urinary purine derivatives (PD) excretion, the ratios of allantoin to creatinine (CR), PD to CR, the plasma urea-N (PUN) and insulin increased in the animals, but the intake of neutral detergent fiber (NDF), the coefficient of whole tract, apparent digestibility of NDF, the transit time (TT) and the mean retention time (TMRT) decreased, when the proportion of concentrate in the diet increased. This study indicated that the proportion of P40:C60 in the diet produced the best efficiency of urinary PD excretion (mmol) per digestible OM intake (kg DOMI).

Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production.

PubMed

Birken, S; Gawinowicz, M A; Maydelman, Y; Milgrom, Y

2001-10-01

The gonadotropins are a family of closely related heterodimeric glycoprotein hormones homologous in structure to disulfide-knot growth factors. Metabolic proteolytic processing in vivo of this disulfide cross-linked region results in urinary excretion of a residual highly stable core structure. The primary structure of the pituitary form of the hLH beta core was reported earlier, but it has proved difficult to isolate the urinary core, although antibodies to the pituitary core demonstrated its presence. By conventional and immunoaffinity methods, the urinary core has been isolated and its structure determined by both chemical and mass spectrometric methods. The urinary hLH beta core is the same as the pituitary-extracted hLH beta core, beta 6-40 disulfide bridged to beta 55-93, except that the pituitary core is more heterogeneous containing also beta 49-93. These findings imply a dual origin of urinary cores, both directly from a secreting tissue and by kidney processing of circulating hormone. We also found that pregnant chimpanzees excrete a CG beta core with a primary structure identical to that of the human CG beta core of pregnancy. In conclusion, gonadotropin core generation and urinary excretion of nearly identical gonadotropin metabolites is common among primates. Although possible biological functions of these core fragments remain unproven, they have diagnostic utility because of their stability and abundance.

Genotoxicity and potential carcinogenicity of 2,4,6-TNT trinitrotoluene: structural and toxicological considerations.

PubMed

Bolt, Hermann M; Degen, Gisela H; Dorn, Susanne B; Plöttner, Sabine; Harth, Volker

2006-01-01

Environmental contamination with 2,4,6-TNT (trinitrotoluene) represents a worldwide problem. Concern for carcinogenicity can be derived from chemically related compounds, especially the dinitrotoluenes. In the metabolism of TNT, the reductive routes are preponderant. The main urinary metabolites of TNT are 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene. In humans exposed to TNT, the formation of hemoglobin adducts of the amino-dinitrotoluenes is in general concordance with the ratio of urinary excretion. The variations in quantities of excreted metabolites among the different occupational cohorts studied are likely explained by the different routes of exposure to TNT, including dermal uptake. Most studies show that urinary excretion of the amino-dinitrotoluenes (4-amino-dinitrotoluene plus 2-amino-dinitrotoluene) in a range of 1 to 10 mg L(-1) (5-50 microM) are not uncommon--for instance in persons employed with the disposal of military waste. Trinitotoluene is mutagenic in Salmonella typhimurium strains TA98 and TA100, with and without exogenous metabolic activation. Mutagenic activity has been found in urine from workers who were occupationally exposed to TNT. An unpublished 2-year study was reported in 1984 by the IIT Research Institute, Chicago, IL. Fischer 344 rats were fed diets containing 0.4, 2.0, 10, or 50 mg/kg TNT per day. In the urinary bladder, hyperplasia (12 of 47 animals p < .01) and carcinoma (11 of 47 animals, p < .05) were observed at significant levels in high-dose (50 mg kg(-1)) females and in one or two females, respectively, at 10 mg kg(-1). Taking all the available evidence together, the appropriate precautions should be taken.

Stereoselectivity of the arene epoxide pathway of mephenytoin hydroxylation in man.

PubMed

Küpfer, A; Lawson, J; Branch, R A

1984-02-01

Stereoselective metabolism of mephenytoin has been investigated in four normal subjects by comparing urinary recoveries of hydroxylated metabolites after administration of racemic RS-mephenytoin (1.4 mmol/day) and R-mephenytoin (0.7 mmol/day) on separate occasions. Gas chromatography-mass spectrometry was employed to measure the urinary recovery of 3-methyl-5-(4-hydroxyphenyl)-5-ethylhydantoin (4-OH-M) and mephenytoin catechol, methylcatechol, and dihydrodiol metabolites. Following a single oral dose of racemic mephenytoin, 4-OH-M, mephenytoin catechol, and methylcatechol metabolites were identified in urine mainly as conjugates, whereas the dihydrodiol metabolite was recovered mainly in its unconjugated form. Urinary elimination of each metabolite was similar on days 1 and 10 of chronic racemic mephenytoin administration. Following R-mephenytoin administration, urinary recoveries of hydroxylated metabolites were five to 10 times smaller than after administration of the racemic drug. This implies substrate-stereoselective hydroxylation of the S-enantiomer of mephenytoin. In one subject with a genetic deficiency of aromatic mephenytoin hydroxylation deficiency, the excretion of each hydroxylated mephenytoin metabolite after RS-mephenytoin administration was decreased to 5-15% of the values found in the four extensively hydroxylating study volunteers. The impaired formation of hydroxylated mephenytoin metabolites in genetic hydroxylation deficiency, in conjunction with stereoselective hydroxylation of S-mephenytoin via an extensive NIH shift in normal man, is consistent with the hypothesis that the formation of the S-mephenytoin arene oxide is under genetic control and represents the initial enzymatic reaction of stereoselective aromatic mephenytoin hydroxylation. The formation of this potentially reactive metabolite of S-mephenytoin may have implications in mephenytoin-induced toxicity.

TISSUE DOSIMETRY, METABOLISM AND EXCRETION OF PENTAVALENT AND TRIVALENT DIMETHYLATED ARSENIC IN MICE AFTER ORAL ADMINISTRATION

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic in mice after acute oral administration. Adult female mice were...

Variability of plasma and urine betaine in diabetes mellitus and its relationship to methionine load test responses: an observational study

PubMed Central

2012-01-01

Background Since betaine is an osmolyte and methyl donor, and abnormal betaine loss is common in diabetes mellitus (>20% patients), we investigated the relationship between betaine and the post-methionine load rise in homocysteine, in diabetes and control subjects. The post-methionine load test is reported to be both an independent vascular risk factor and a measure of betaine sufficiency. Methods Patients with type 2 diabetes (n = 34) and control subjects (n = 17) were recruited. We measured baseline fasting plasma and 4-hour post-methionine load (L-methionine, 0.1 mg/kg body weight) concentrations of homocysteine, betaine, and the betaine metabolite N,N-dimethylglycine. Baseline urine excretions of betaine, dimethylglycine and glucose were measured on morning urine samples as the ratio to urine creatinine. Statistical determinants of the post-methionine load increase in homocysteine were identified in multiple linear regression models. Results Plasma betaine concentrations and urinary betaine excretions were significantly (p < 0.001) more variable in the subjects with diabetes compared with the controls. Dimethylglycine excretion (p = 0.00014) and plasma dimethylglycine concentrations (p = 0.039) were also more variable. In diabetes, plasma betaine was a significant negative determinant (p < 0.001) of the post-methionine load increase in homocysteine. However, it was not conclusive that this was different from the relationship in the controls. In the patients with diabetes, a strong relationship was found between urinary betaine excretion and urinary glucose excretion (but not with plasma glucose). Conclusions Both high and low plasma betaine concentrations, and high and low urinary betaine excretions, are more prevalent in diabetes. The availability of betaine affects the response in the methionine load test. The benefits of increasing betaine intake should be investigated. PMID:22510294

Relation of melatonin to sleep architecture in children with autism.

PubMed

Leu, Roberta M; Beyderman, Liya; Botzolakis, Emmanuel J; Surdyka, Kyla; Wang, Lily; Malow, Beth A

2011-04-01

Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum disorders (ASD). Twenty-three children, aged 4-10 years, completed two nights of polysomnography and one overnight urine collection for measurement of urinary 6-SM excretion rate. Parents completed the Children's Sleep Habits Questionnaire. We found that higher urinary 6-SM excretion rates were associated with increased N3 sleep, decreased N2 sleep, and decreased daytime sleepiness. The results warrant further examination to examine the effects of supplemental melatonin on sleep architecture and daytime sleepiness.

Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage.

PubMed

Moos, Rebecca K; Angerer, Jürgen; Dierkes, Georg; Brüning, Thomas; Koch, Holger M

2016-11-01

Parabens are used as preservatives in personal care and consumer products, food and pharmaceuticals. Their use is controversial because of possible endocrine disrupting properties. In this study, we investigated metabolism and urinary excretion of methyl paraben (MeP), iso-butyl paraben (iso-BuP) and n-butyl paraben (n-BuP) after oral dosage of deuterium-labeled analogs (10 mg). Each volunteer received one dosage per investigated paraben separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h. In addition to the parent parabens (free and conjugated) which are already used as biomarkers of internal exposure and the known but non-specific metabolites, p-hydroxybenzoic acid (PHBA) and p-hydroxyhippuric acid (PHHA), we identified new, oxidized metabolites with hydroxy groups on the alkyl side chain (3OH-n-BuP and 2OH-iso-BuP) and species with oxidative modifications on the aromatic ring. MeP represented 17.4 % of the dose excreted in urine, while iso-BuP represented only 6.8 % and n-BuP 5.6 %. Additionally, for iso-BuP, about 16 % was excreted as 2OH-iso-BuP and for n-BuP about 6 % as 3OH-n-BuP. Less than 1 % was excreted as ring-hydroxylated metabolites. In all cases, PHHA was identified as the major but non-specific metabolite (57.2-63.8 %). PHBA represented 3.0-7.2 %. For all parabens, the majority of the oral dose captured by the above metabolites was excreted in the first 24 h (80.5-85.3 %). Complementary to the parent parabens excreted in urine, alkyl-chain-oxidized metabolites of the butyl parabens are introduced as valuable and contamination-free biomarkers of exposure.

Colonic catabolism of dietary phenolic and polyphenolic compounds from Concord grape juice.

PubMed

Stalmach, Angelique; Edwards, Christine A; Wightman, Jolynne D; Crozier, Alan

2013-01-01

After acute ingestion of 350 ml of Concord grape juice, containing 528 μmol of (poly)phenolic compounds, by healthy volunteers, a wide array of phase I and II metabolites were detected in the circulation and excreted in urine. Ingestion of the juice by ileostomists resulted in 40% of compounds being recovered intact in ileal effluent. The current study investigated the fate of these undigested (poly)phenolic compounds on reaching the colon. This was achieved through incubation of the juice using an in vitro model of colonic fermentation and through quantification of catabolites produced after colonic degradation and their subsequent absorption prior to urinary excretion by healthy subjects and ileostomy volunteers. A total of 16 aromatic and phenolic compounds derived from colonic metabolism of Concord grape juice (poly)phenolic compounds were identified by GC-MS in the faecal incubation samples. Thirteen urinary phenolic acids and aromatic compounds were excreted in significantly increased amounts after intake of the juice by healthy volunteers, whereas only two of these compounds were excreted in elevated amounts by ileostomists. The production of phenolic acids and aromatic compounds by colonic catabolism contributed to the bioavailability of Concord grape (poly)phenolic compounds to a much greater extent than phase I and II metabolites originating from absorption in the upper gastrointestinal tract. Catabolic pathways are proposed, highlighting the impact of colonic microbiota and subsequent phase II metabolism prior to excretion of phenolic compounds derived from (poly)phenolic compounds in Concord grape juice, which pass from the small to the large intestine.

Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport Mechanisms.

PubMed

Li, Yong; Sekula, Peggy; Wuttke, Matthias; Wahrheit, Judith; Hausknecht, Birgit; Schultheiss, Ulla T; Gronwald, Wolfram; Schlosser, Pascal; Tucci, Sara; Ekici, Arif B; Spiekerkoetter, Ute; Kronenberg, Florian; Eckardt, Kai-Uwe; Oefner, Peter J; Köttgen, Anna

2018-05-01

Background The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be altered in CKD. Genetic studies of metabolite concentrations can identify proteins performing these functions. Methods We conducted genome-wide association studies and aggregate rare variant tests of the concentrations of 139 serum metabolites and 41 urine metabolites, as well as their pairwise ratios and fractional excretions in up to 1168 patients with CKD. Results After correction for multiple testing, genome-wide significant associations were detected for 25 serum metabolites, two urine metabolites, and 259 serum and 14 urinary metabolite ratios. These included associations already known from population-based studies. Additional findings included an association for the uremic toxin putrescine and variants upstream of an enzyme catalyzing the oxidative deamination of polyamines ( AOC1 , P -min=2.4×10 -12 ), a relatively high carrier frequency (2%) for rare deleterious missense variants in ACADM that are collectively associated with serum ratios of medium-chain acylcarnitines ( P -burden=6.6×10 -16 ), and associations of a common variant in SLC7A9 with several ratios of lysine to neutral amino acids in urine, including the lysine/glutamine ratio ( P =2.2×10 -23 ). The associations of this SLC7A9 variant with ratios of lysine to specific neutral amino acids were much stronger than the association with lysine concentration alone. This finding is consistent with SLC7A9 functioning as an exchanger of urinary cationic amino acids against specific intracellular neutral amino acids at the apical membrane of proximal tubular cells. Conclusions Metabolomic indices of specific kidney functions in genetic studies may provide insight into human renal physiology. Copyright © 2018 by the American Society of Nephrology.

Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats.

PubMed

Shibata, Katsumi; Morita, Nobuya; Kawamura, Tomoyo; Tsuji, Ai; Fukuwatari, Tsutomu

2015-01-01

Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically. Niacin and its metabolites in the liver, blood, and urine were affected as expected. Although the concentrations of vitamin B1, pantothenic acid, folate, and biotin in liver and blood were decreased by orotic acid-induced fatty liver, these urinary excretion amounts showed a specific pattern toward increase. Generally, as for the typical urinary excretion of B-group vitamins, these are excreted when the body is saturated. However, the ability to sustain vitamin B1, pantothenic acid, folate, and biotin decreased in fatty liver, which is hypothesized as a specific phenomenon. This metabolic response might occur to prevent an abnormally increased biosynthesis of fatty acids by orotic acid.

Major furocoumarins in grapefruit juice I: levels and urinary metabolite(s).

PubMed

Messer, Anastasia; Nieborowski, Anna; Strasser, Christian; Lohr, Christiane; Schrenk, Dieter

2011-12-01

Furocoumarins are phototoxic and photogenotoxic natural plant constituents occurring in cosmetics, food and drugs. Grapefruit juice is considered as a major dietary source of furocoumarins although few is known about the variability of furocoumarins in grapefruit juice. We analyzed the major furocoumarins in eight commercial grapefruit juices and in freshly prepared juices made from pink grapefruit obtained from German retailers. Bergaptol was the major furocoumarin in commercial juices, followed by bergamottin and 6',7'-dihydroxy-bergamottin (DHB), whereas an inverse picture (DHB>bergamottin>bergaptol) was obtained in freshly prepared juices. Results from different batches of a single brand of commercial juice, purchased over a period of 7 months, revealed a variability of about 50% for the individual furocoumarins and the sum. In a study with healthy volunteers, consumption of 900 ml commercial grapefruit juice (containing 12.5mg bergaptol, 6.9 mg bergamottin, and 0.6 mg DHB) resulted in an average urinary excretion of 0.36 mg free plus 13.23 mg conjugated bergaptol within 6h. Other furocoumarins were not found in urine. Thus, other grapefruit furocoumarins were obviously converted in the human body, at least in part, into bergaptol excreted in urine, since the excreted amount of bergaptol exceeded the consumed one. Copyright © 2011 Elsevier Ltd. All rights reserved.

Urinary metabolites from mango (Mangifera indica L. cv. Keitt) galloyl derivatives and in vitro hydrolysis of gallotannins in physiological conditions.

PubMed

Barnes, Ryan C; Krenek, Kimberly A; Meibohm, Bernd; Mertens-Talcott, Susanne U; Talcott, Stephen T

2016-03-01

The absorption, metabolism, and excretion of mango galloyl derivatives (GD) has not yet been investigated in humans, and studies investigating repeated dosages of polyphenols are limited. In this human pilot trial, healthy volunteers (age = 21-38 y, n = 11) consumed 400 g/day of mango-pulp (cv. Keitt) for 10 days, and seven metabolites of gallic acid (GA) were characterized and quantified in urine excreted over a 12 h period. Pyrogallol-O-sulfate and deoxypyrogallol-O-sulfate were found to be significantly more excreted between days 1 and 10 (p < 0.05) from 28.5 to 55.4 mg and 23.6 to 47.7 mg, respectively. Additionally, the in vitro hydrolysis of gallotannins (GTs) was monitored at physiological pH and temperature conditions, and after 4 h a significant (p < 0.05) shift in composition from relativity high to low molecular weight GTs was observed. Seven metabolites of GA were identified in the urine of healthy volunteers, and two microbial metabolites were found to be significantly more excreted following 10 days of mango consumption. Mango GTs were also found to release free GA in conditions similar to the intestines. GTs may serve as a pool of pro-GA compounds that can be absorbed or undergo microbial metabolism. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolism of the hydrochlorofluorocarbon 1,2-dichloro-1,1-difluoroethane.

PubMed

Harris, J W; Anders, M W

1991-01-01

1,2-Dichloro-1,1-difluoroethane (HCFC-132b) is a potential substitute for some ozone-depleting chlorofluorocarbons and a model for other 1,1,1,2-tetrahaloethanes under consideration as chlorofluorocarbon substitutes. Male Fischer 344 rats were given 10 mmol/kg HCFC-132b dissolved in corn oil by intraperitoneal injection. An NMR assay for covalent binding of HCFC-132b metabolites to liver proteins was negative, whereas binding was observed in halothane-treated rats. Total urinary metabolites excreted by rats given HCFC-132b during the first 24 h amounted to 1.8 +/- 0.1% of the injected dose, as determined by 19F NMR. During the first 6 h, metabolites of HCFC-132b corresponding to 2-chloro-2,2-difluoroethyl glucuronide, unknown metabolite A, chlorodifluoroacetic acid, and chlorodifluoroacetaldehyde hydrate [both free and conjugated (unknown metabolite B)] were excreted in urine in the approximate ratio 100:9:3:7, respectively. Metabolite A is apparently an O-conjugate of 2-chloro-2,2-difluoroethanol; unconjugated 2-chloro-2,2-difluoroethanol was not detected in urine. The 19F NMR spectrum of metabolite B indicates the formation of a hemiacetal of chlorodifluoroacetaldehyde. Repeated exposure of rats to HCFC-132b significantly increased both the rate of chlorodifluoroacetic acid excretion and the relative fraction of the HCFC-132b dose excreted as chlorodifluoroacetic acid in urine. Incubation of HCFC-132b with rat hepatic microsomes yielded chlorodifluoroacetaldehyde hydrate as the only fluorinated product. The in vitro metabolism of HCFC-132b was increased in microsomes from pyridine-treated rats as compared with control rats, and HCFC-132b metabolism was inhibited by p-nitrophenol, indicating that the cytochrome P-450 isoform IIE1 is largely responsible for the initial hydroxylation of HCFC-132b.

New insights into the bioavailability of red raspberry anthocyanins and ellagitannins.

PubMed

Ludwig, Iziar A; Mena, Pedro; Calani, Luca; Borges, Gina; Pereira-Caro, Gema; Bresciani, Letizia; Del Rio, Daniele; Lean, Michael E J; Crozier, Alan

2015-12-01

Red raspberries, containing ellagitannins and cyanidin-based anthocyanins, were fed to volunteers and metabolites appearing in plasma and urine were analysed by UHPLC-MS. Anthocyanins were not absorbed to any extent with sub nmol/L concentrations of cyanidin-3-O-glucoside and a cyanidin-O-glucuronide appearing transiently in plasma. Anthocyanins excreted in urine corresponded to 0.007% of intake. More substantial amounts of phase II metabolites of ferulic acid and isoferulic acid, along with 4'-hydroxyhippuric acid, potentially originating from pH-mediated degradation of cyanidin in the proximal gastrointestinal tract, appeared in urine and also plasma where peak concentrations were attained 1-1.5h after raspberry intake. Excretion of 18 anthocyanin-derived metabolites corresponded to 15.0% of intake, a figure substantially higher than obtained in other anthocyanin feeding studies. Ellagitannins pass from the small to the large intestine where the colonic microbiota mediate their conversion to urolithins A and B which appeared in plasma and were excreted almost exclusively as sulfate and glucuronide metabolites. The urolithin metabolites persisted in the circulatory system and were excreted in urine for much longer periods of time than the anthocyanin metabolites although their overall urinary recovery was lower at 7.0% of intake. It is events originating in the proximal and distal gastrointestinal tract, and subsequent phase II metabolism, that play an important role in the bioavailability of both anthocyanins and ellagitannins and it is their metabolites which appear in the circulatory system, that are key to elucidating the mode of action(s) underlying the protective effects of these compounds on human health. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of atmospheric concentrations of polycyclic aromatic hydrocarbons with their urinary metabolites in children and adolescents.

PubMed

Poursafa, Parinaz; Amin, Mohammad Mehdi; Hajizadeh, Yaghoub; Mansourian, Marjan; Pourzamani, Hamidreza; Ebrahim, Karim; Sadeghian, Babak; Kelishadi, Roya

2017-07-01

This study aims to determine the atmospheric concentrations of particulate matter 2.5 (PM 2.5 )-bounded polycyclic aromatic hydrocarbons (PAHs) and their association with their urinary metabolites in children and adolescents. This study was conducted from October 2014 to March 2016 in Isfahan, Iran. We measured 16 species of PAHs bounded to PM 2.5 by gas chromatography mass spectrometry (GC/MS) from 7 parts of the city. Moreover, PAH urinary metabolites were measured in 186 children and adolescents, randomly selected from households. Urinary metabolites consisted of 1-hydroxy naphthalene (1-naphthol), 2-hydroxy naphthalene (2-naphthol), 9-hydroxy phenanthrene (9-phenanthrol), and 1-hydroxy pyrene using GC/MS. Considering the short half-lives of PAHs, we measured the metabolites twice with 4 to 6 months of time interval. We found that the ambient concentrations of PAHs were significantly associated with their urinary metabolites. 1-hydroxy naphthalene and 2-hydroxy naphthalene concentrations showed an increase of 1.049 (95% CI: 1.030, 1.069) and 1.047 (95% CI: 1.025, 1.066) for each unit increase (1 ng/m 3 ) in ambient naphthalene. Similarly, 1-hydroxy pyrene showed an increase of 1.009 (95% CI: 1.006-1.011) for each unit increase (1 ng/m 3 ) in ambient pyrene concentration after adjustment for body mass index, physical activity level, urinary creatinine, age, and sex. The association of urinary 9-hydroxyphenanthrene and ambient phenantherene was significant in the crude model; however after adjustment for the abovementioned covariates, it was no more significant. We found significant correlations between exposure to ambient PM 2.5 -bounded PAHs and their urinary excretion. Considering the adverse health effects of PAHs in the pediatric age group, biomonitoring of PAHs should be underscored; preventive measures need to be intensified.

Pyridoxic acid excretion during low vitamin B-6 intake, total fasting, and bed rest

NASA Technical Reports Server (NTRS)

Coburn, S. P.; Thampy, K. G.; Lane, H. W.; Conn, P. S.; Ziegler, P. J.; Costill, D. L.; Mahuren, J. D.; Fink, W. J.; Pearson, D. R.; Schaltenbrand, W. E.

1995-01-01

Vitamin B-6 metabolism in 10 volunteers during 21 d of total fasting was compared with results from 10 men consuming a diet low only in vitamin B-6 (1.76 mumol/d) and with men consuming a normal diet during bed rest. At the end of the fast mean plasma concentrations of vitamin B-6 metabolites and urinary excretion of 4-pyridoxic acid tended to be higher in the fasting subjects than in the low-vitamin B-6 group. The fasting subjects lost approximately 10% of their total vitamin B-6 pool and approximately 13% of their body weight. The low-vitamin B-6 group lost only approximately 4% of their vitamin B-6 pool. Compared with baseline, urinary excretion of pyridoxic acid was significantly increased during 17 wk of bed rest. There was no increase in pyridoxic acid excretion during a second 15-d bed rest study. These data suggest the possibility of complex interactions between diet and muscle metabolism that may influence indexes that are frequently used to assess vitamin B-6 status.

Relation of Melatonin to Sleep Architecture in Children with Autism

PubMed Central

Leu, Roberta M.; Beyderman, Liya; Botzolakis, Emmanuel J.; Surdyka, Kyla; Wang, Lily; Malow, Beth A.

2013-01-01

Children with autism often suffer from sleep disturbances, and compared to age-matched controls, have decreased melatonin levels, as indicated by urine levels of the primary melatonin metabolite, 6-sulfatoxymelatonin (6-SM). We therefore investigated the relationship between 6-SM levels and sleep architecture in children with autism spectrum disorders (ASD). Twenty-three children, aged 4–10 years, completed two nights of polysomnography and one overnight urine collection for measurement of urinary 6-SM excretion rate. Parents completed the Children’s Sleep Habits Questionnaire. We found that higher urinary 6-SM excretion rates were associated with increased N3 sleep, decreased N2 sleep, and decreased daytime sleepiness. The results warrant further examination to examine the effects of supplemental melatonin on sleep architecture and daytime sleepiness. PMID:20683768

Effects of biological and behavioral factors on urinary arsenic ...

EPA Pesticide Factsheets

Abstract In older men and women who were long-term residents of Churchill County, Nevada, we examined the relation between arsenic exposure from home tap water and urinary levels of inorganic arsenic and its methylated metabolites. Over a wide exposure range (up to 1850 ug of arsenic per liter), urinary concentrations of inorganic, monomethylated, and dimethylated arsenicals strongly correlated with home tap water arsenic concentrations. However, percentages of summed urinary concentrations of inorganic, monomethylated, and dimethylated arsenicals accounted for by each arsenical species were unaffected by arsenic concentration in home tap water, suggesting thc1t capacity for formation and excretion of methylated metabolites was not exceeded. Biological factors (gender, age, body mass index, and genotype) and a behavioral factor (smoking) influenced absolute and relative levels of arsenicals in urine. A multivariate regression model showed that both biological and behavioral factors were significant predictors of absolute and relative concentrations of inorganic arsenic and its methylated metabolites in urine. These findings suggest that analyses of dose-response relations in arsenic-exposed populations should account for these biological and behavioral factors. Furthermore, evidence of significant effects of these factors on arsenic metabolism may support mode of action studies in appropriate experimental models. Running title- Methylated arsenicals as urinary b

Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

PubMed

Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

2018-07-01

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

Urinary 2,5-hexanedione excretion in cryptogenic polyneuropathy compared to the general Swedish population

PubMed Central

2013-01-01

Background 2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors. Methods Morning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis. Results Cases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age. Conclusions Significantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however. PMID:23898939

Urinary excretion levels of water-soluble vitamins in pregnant and lactating women in Japan.

PubMed

Shibata, Katsumi; Fukuwatari, Tsutomu; Sasaki, Satoshi; Sano, Mitsue; Suzuki, Kahoru; Hiratsuka, Chiaki; Aoki, Asami; Nagai, Chiharu

2013-01-01

Recent studies have shown that the urinary excretion levels of water-soluble vitamins can be used as biomarkers for the nutritional status of these vitamins. To determine changes in the urinary excretion levels of water-soluble vitamins during pregnant and lactating stages, we surveyed and compared levels of nine water-soluble vitamins in control (non-pregnant and non-lactating women), pregnant and lactating women. Control women (n=37), women in the 2nd (16-27 wk, n=24) and 3rd trimester of pregnancy (over 28 wk, n=32), and early- (0-5 mo, n=54) and late-stage lactating (6-11 mo, n=49) women took part in the survey. The mean age of subjects was ~30 y, and mean height was ~160 cm. A single 24-h urine sample was collected 1 d after the completion of a validated, self-administered comprehensive diet history questionnaire to measure water-soluble vitamins or metabolites. The average intake of each water-soluble vitamin was ≍ the estimated average requirement value and adequate intake for the Japanese Dietary Reference Intakes in all life stages, except for vitamin B6 and folate intakes during pregnancy. No change was observed in the urinary excretion levels of vitamin B2, vitamin B6, vitamin B12, biotin or vitamin C among stages. Urine nicotinamide and folate levels were higher in pregnant women than in control women. Urine excretion level of vitamin B1 decreased during lactation and that of pantothenic acid decreased during pregnancy and lactation. These results provide valuable information for setting the Dietary Reference Intakes of water-soluble vitamins for pregnant and lactating women.

Assessment of exposure to organophosphate insecticides during spraying in Haiti: monitoring of urinary metabolites and blood cholinesterase levels*

PubMed Central

Warren, McWilson; Spencer, Harrison C.; Churchill, Frederick C.; Francois, Velly Jean; Hippolyte, Robert; Staiger, Michael A.

1985-01-01

Measurement of blood cholinesterase activity and of the urinary metabolites of fenitrothion (p-nitrocresol) and malathion (monocarboxylic acid) was used to assess the exposure to these insecticides of workers in the Haitian malaria control programme and of residents in the sprayed houses. Cholinesterase activity was significantly reduced at the end of the working week in 3 out of 28 fenitrothion workers. Urinary levels of p-nitrocresol (PNC) in the spraymen ranged from 2.2 to 25.2 mg/l. In fenitrothion workers who had no direct contact with spraying (weighers and supervisors), the cholinesterase activity remained ≥ 75% of the normal control value, and the urinary PNC levels were relatively low. Urinary malathion monocarboxylic acid (MCA) levels at the end of the working week ranged between 1.1 and 5.3 mg/l in workers using malathion and their blood cholinesterase activity remained essentially normal. In both groups of workers the cholinesterase levels improved and the urinary excretion of metabolites decreased after 2 days of rest from the spraying operations. In the residents of the sprayed houses, low concentrations of PNC and MCA were detected in the urine 1 day after spraying and measurable but reduced levels were still present after 7 days. In all these cases the cholinesterase activity remained ≥ 75% of the normal control value. PMID:3874716

Quantitative Measurement of JWH-018 and JWH-073 Metabolites Excreted in Human Urine

PubMed Central

Moran, Cindy L.; Le, Vi-Huyen; Chimalakonda, Krishna C.; Smedley, Amy L.; Lackey, Felisia D.; Owen, Suzanne N.; Kennedy, Paul D.; Endres, Gregory W.; Ciske, Fred L.; Kramer, James B.; Kornilov, Andrei M.; Bratton, L. D.; Dobrowolski, Paul J.; Wessinger, William D.; Fantegrossi, William E.; Prather, Paul P.; James, Laura P.; Radominska-Pandya, Anna; Moran, Jeffery H.

2011-01-01

'K2/SPICE' products are commonly laced with aminoalkylindole synthetic cannabinoids (i.e., JWH-018 and JWH-073) and are touted as ‘legal’ marijuana substitutes. Here we validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) methsod for measuring urinary concentrations of JWH-018, JWH-073, and several potential metabolites of each. The analytical procedure has high capacity for sample throughput and does not require solid phase or liquid extraction. Evaluation of human urine specimens collected after the subjects reportedly administered JWH-018 or a mixture of JWH-018 and JWH-073 provides preliminary evidence of clinical utility. Two subjects that consumed JWH-018 primarily excreted glucuronidated conjugates of 5-(3-(1-naphthoyl)-1H-indol-1-yl)-pentanoic acid (> 50 ng/ml) and (1-(5-hydroxypentyl)- 1H -indol-3-yl)(naphthalene-1-yl)-methanone (> 30 ng/ml). Interestingly, oxidized metabolites of both JWH-018 and JWH-073 were detected in these specimens, suggesting either metabolic demethylation of JWH-018 to JWH-073 or a non-reported, previous JWH-073 exposure. Metabolic profiles generated from a subject who consumed a mixture of JWH-018 and JWH-073 were similar to profiles generated from subjects who presumably consumed JWH-018 exclusively. Oxidized metabolites of JWH-018 and JWH-073 were of the same pattern, but JWH-018 metabolites were excreted at lower concentrations. These results begin clinically validating the LC-MS/MS assay for detecting and quantifying aminoalkylindole metabolites. Full validation awaits further testing. PMID:21506519

Pharmacokinetics, distribution, metabolism, and excretion of the dual reuptake inhibitor [(14)C]-nefopam in rats.

PubMed

Yu, Jian; Solon, Eric; Shen, Helen; Modi, Nishit B; Mittur, Aravind

2016-11-01

1. This study examined the pharmacokinetics, distribution, metabolism, and excretion of [(14)C] nefopam in rats after a single oral administration. Blood, plasma, and excreta were analyzed for total radioactivity, nefopam, and metabolites. Metabolites were profiled and identified. Radioactivity distribution was determined by quantitative whole-body autoradiography. 2. The pharmacokinetic profiles of total radioactivity and nefopam were similar in male and female rats. Radioactivity partitioned approximately equally between plasma and red blood cells. A majority of the radioactivity was excreted in urine within 24 hours and mass balance was achieved within 7 days. 3. Intact nefopam was a minor component in plasma and excreta. Numerous metabolites were identified in plasma and urine generated by multiple pathways including: hydroxylation/oxidation metabolites (M11, M22a and M22b, M16, M20), some of which were further glucuronidated (M6a to M6c, M7a to M7c, M8a and M8b, M3a to M3d); N-demethylation of nefopam to metabolite M21, which additionally undergoes single or multiple hydroxylations or sulfation (M9, M14, M23), with some of the hydroxylated metabolites further glucuronidated (M2a to M2d). 4. Total radioactivity rapidly distributed with highest concentrations found in the urinary bladder, stomach, liver, kidney medulla, small intestine, uveal tract, and kidney cortex without significant accumulation or persistence. Radioactivity reversibly associated with melanin-containing tissues.

CHLORPYRIFOS ACCUMULATION PATTERNS FOR CHILD ACCESSIBLE SURFACES AND OBJECTIVES AND URINARY METABOLITE EXCRETION BY CHILDREN FOR TWO-WEEKS AFTER CRACK-AND-CREVICE APPLICATION

EPA Science Inventory

The Children's-Post-Pesticide-Application-Exposure-Study (CPPAES) was conducted to look at the distribution of chlorpyrifos within a home environment for a 2-week period following a routine professional crack-and-crevice application, and to determine the amount of the chlorpyrifo...

Comparative acute nephrotoxicity of salicylic acid, 2,3-dihydroxybenzoic acid, and 2,5-dihydroxybenzoic acid in young and middle aged Fischer 344 rats.

PubMed

McMahon, T F; Stefanski, S A; Wilson, R E; Blair, P C; Clark, A M; Birnbaum, L S

1991-03-11

Experimental evidence suggests that the oxidative metabolites 2,3- and 2,5-dihydroxybenzoic acid (DIOH) may be responsible for the nephrotoxicity of salicylic acid (SAL). In the present study, enzymuria in conjunction with glucose (GLU) and protein (PRO) excretion were used as endpoints to compare the relative nephrotoxicity of SAL with 2,3- and 2,5-DIOH. In addition, the effect of age on enzymuria and GLU and PRO excretion following treatment with SAL or 2,3- and 2,5-DIOH was investigated because the elderly are at greater risk for SAL-induced nephrotoxicity. Three and 12-month male Fischer 344 rats were administered either no treatment, vehicle, SAL, 2,3-DIOH, or 2,5-DIOH at 500 mg/kg p.o. in 5 ml/kg corn oil/DMSO (5:1). Effects of these treatments on functional integrity of renal tissue was assessed from 0--72 h after dosing by measurement of urinary creatinine, GLU, and PRO, as well as excretion of proximal and distal tubular renal enzymes. Enzymes measured as indicators of proximal tubular damage were N-acetyl-beta-glucosaminidase (NAG), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), and alkaline phosphatase (AP), while urinary lactate dehydrogenase (LD) and aspartate aminotransferase (AST) were measured as indicators of distal tubular damage. In comparison to 3-month vehicle-treated rats, 2,3- and 2,5-DIOH caused a significant increase between 0-8 h in excretion of urinary GLU and activities of AST, NAG, and LD, with peak effects occurring between 4-8 h. Toxic effects of either metabolite were not evident beyond 24 h, and toxicity of 2,5-DIOH was significantly greater in comparison to 2,3-DIOH. SAL treatment resulted in similar effects on enzymuria as well as GLU and PRO excretion, but peak effects did not occur until 16-24 h, and often persisted until 72 h after dosing. Maximal enzymuria in response to SAL treatment was significantly greater in 12- vs. 3-month rats for AST, NAG, and LD. In response to 2,3-DIOH treatment, the maximal response was significantly greater in 12- vs. 3-month rats for LD and AST, and for NAG in response to 2,5-DIOH treatment. The results of this study suggest that both 2,3- and 2,5-DIOH are nephrotoxic metabolites of SAL, but implicate 2,5-DIOH as the more potent nephrotoxic metabolite. The relative lack of an age effect for 2,3- and 2,5-DIOH vs. SAL supports the hypothesis [2] that age-related differences in biotransformation of SAL, and not increased tissue sensitivity to 2,3- or 2,5-DIOH, contribute to the age-related increase in susceptibility to SAL-induced nephrotoxicity.

Relation of dietary inorganic arsenic exposure and urinary inorganic arsenic metabolites excretion in Japanese subjects.

PubMed

Oguri, Tomoko; Yoshinaga, Jun; Suzuki, Yayoi; Tao, Hiroaki; Nakazato, Tetsuya

2017-06-03

Inorganic arsenic (InAs) is a ubiquitous metalloid that has been shown to exert multiple adverse health outcomes. Urinary InAs and its metabolite concentration has been used as a biomarker of arsenic (As) exposure in some epidemiological studies, however, quantitative relationship between daily InAs exposure and urinary InAs metabolites concentration has not been well characterized. We collected a set of 24-h duplicated diet and spot urine sample of the next morning of diet sampling from 20 male and 19 female subjects in Japan from August 2011 to October 2012. Concentrations of As species in duplicated diet and urine samples were determined by using liquid chromatography-ICP mass spectrometry with a hydride generation system. Sum of the concentrations of urinary InAs and methylarsonic acid (MMA) was used as a measure of InAs exposure. Daily dietary InAs exposure was estimated to be 0.087 µg kg -1 day -1 (Geometric mean, GM), and GM of urinary InAs+MMA concentrations was 3.5 ng mL -1 . Analysis of covariance did not find gender-difference in regression coefficients as significant (P > 0.05). Regression equation Log 10 [urinary InAs+MMA concentration] = 0.570× Log 10 [dietary InAs exposure level per body weight] + 1.15 was obtained for whole data set. This equation would be valuable in converting urinary InAs concentration to daily InAs exposure, which will be important information in risk assessment.

Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Lili; Southern Yangtze University, Wuxi; Guan Hongxia

Modulation by lycopene of aflatoxin B{sub 1} (AFB{sub 1})-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB{sub 1} (250 {mu}g/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB{sub 1} (250 {mu}g/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB{sub 1} and greatly modulated AFB{sub 1} metabolism andmore » metabolic activation. Urinary excretion of AFB{sub 1} phase 1 metabolites, AFM{sub 1}, AFQ{sub 1}, and AFP{sub 1}, was significantly decreased in lycopene-treated animals. Formation of serum AFB{sub 1}-albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p < 0.05) to 67.7% on day 15 (p < 0.001). Lycopene intervention also significantly reduced formation of AFB{sub 1}-DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p < 0.05). Levels of AFB{sub 1}-N {sup 7}-guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB{sub 1}-mecapturic acid, was significantly increased in lycopene-intervened animals. AFB{sub 1}-induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene.« less

Prevalence of the equol-producer phenotype and its relationship with dietary isoflavone and serum lipids in healthy Chinese adults.

PubMed

Liu, Baohua; Qin, Liqiang; Liu, Aiping; Uchiyama, Shigeto; Ueno, Tomomi; Li, Xuetuo; Wang, Peiyu

2010-01-01

Studies have suggested that daidzein-metabolizing phenotypes have beneficial effects on a range of health outcomes. We investigated the prevalence of equol producers and the relationship of equol phenotype with habitual isoflavone consumption and serum lipid concentrations in 200 Chinese adults in Beijing. After the baseline survey and dietary records, 200 healthy adults in Beijing were challenged with a soy-isoflavone supplement for 3 days; 24-hour urine samples were collected before and after the challenge. Isoflavones and their metabolites in urine were measured to determine equol phenotype. Serum lipids, uric acid, and other biochemical markers were also measured. Only 26.8% of the participants excreted equol when on a regular diet, as compared with 60.4% after the challenge. After the challenge, urinary isoflavonoid excretion increased in all participants, while equol excretion increased only in equol producers. Isoflavone intake was correlated with urinary isoflavone (range r = 0.49-0.58, P < 0.01). As compared with nonproducers, equol producers were less likely to consume cereals (P < 0.001). There was no significant correlation between serum lipids and isoflavone intake. Serum lipids were not significantly affected by equol phenotype. Urinary equol excretion was detected in about 25% of participants under their usual dietary conditions. Their potential to produce equol was increased after the challenge. Urinary isoflavone levels may serve as a useful biomarker for isoflavone intake in populations. We observed an association between equol phenotype and cereal intake. Our findings also suggest that dietary isoflavone intake has no significant effect on serum lipids in healthy participants, regardless of equol phenotype.

Oral intake of ranitidine increases urinary excretion of N-nitrosodimethylamine.

PubMed

Zeng, Teng; Mitch, William A

2016-06-01

The H2-receptor antagonist, ranitidine, is among the most widely used pharmaceuticals to treat gastroesophageal reflux disease and peptic ulcers. While previous studies have demonstrated that amines can form N-nitrosamines when exposed to nitrite at stomach-relevant pH, N-nitrosamine formation from ranitidine, an amine-based pharmaceutical, has not been demonstrated under these conditions. In this work, we confirmed the production of N-nitrosodimethylamine (NDMA), a potent carcinogen, by nitrosation of ranitidine under stomach-relevant pH conditions in vitro We also evaluated the urinary NDMA excretion attributable to ingestion of clinically used ranitidine doses. Urine samples collected from five female and five male, healthy adult volunteers over 24-h periods before and after consumption of 150mg ranitidine were analyzed for residual ranitidine, ranitidine metabolites, NDMA, total N-nitrosamines and dimethylamine. Following ranitidine intake, the urinary NDMA excreted over 24h increased 400-folds from 110 to 47 600ng, while total N-nitrosamines increased 5-folds. NDMA excretion rates after ranitidine intake equaled or exceeded those observed previously in patients with schistosomiasis, a disease wherein N-nitrosamines are implicated as the etiological agents for bladder cancer. Due to metabolism within the body, urinary NDMA measurements represent a lower-bound estimate of systemic NDMA exposure. Our results suggest a need to evaluate the risks attributable to NDMA associated with chronic consumption of ranitidine, and to identify alternative treatments that minimize exposure to N-nitrosamines. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.

PubMed

Clerici, C; Gentili, G; Boschetti, E; Santucci, C; Aburbeh, A G; Natalini, B; Pellicciari, R; Morelli, A

1994-12-01

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.

Effect of milk on the urinary excretion of microbial phenolic acids after cocoa powder consumption in humans.

PubMed

Urpi-Sarda, Mireia; Llorach, Rafael; Khan, Nasiruddin; Monagas, Maria; Rotches-Ribalta, Maria; Lamuela-Raventos, Rosa; Estruch, Ramon; Tinahones, Francisco J; Andres-Lacueva, Cristina

2010-04-28

Health effects of cocoa flavonols depend on their bioavailability, which is strongly influenced by the food matrix and the degree of flavanol polymerization. The effect of milk on the bioavailability of cocoa flavanoids considering phase II metabolites of epicatechin has been the subject of considerable debate. This work studies the effect of milk at the colonic microbial metabolism level of the nonabsorbed flavanol fraction that reaches the colon and is metabolized by the colonic microbiota into various phenolic acids. Twenty-one human volunteers followed a diet low in polyphenols for at least 48 h before taking, in a random order, 40 g of cocoa powder dissolved either in 250 mL of whole milk or in 250 mL of water. Urine samples were collected before the intake and during three different periods (0-6, 6-12, and 12-24 h). Phenolic acids were analyzed by LC-MS/MS after solid-phase extraction. Of the 15 metabolites assessed, the excretion of 9 phenolic acids was affected by the intake of milk. The urinary concentration of 3,4-dihydroxyphenylacetic, protocatechuic, 4-hydroxybenzoic, 4-hydroxyhippuric, hippuric, caffeic, and ferulic acids diminished after the intake of cocoa with milk, whereas urinary concentrations of vanillic and phenylacetic acids increased. In conclusion, milk partially affects the formation of microbial phenolic acids derived from the colonic degradation of procyanidins and other compounds present in cocoa powder.

Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period.

PubMed

McEntyre, Christopher J; Lever, Michael; Chambers, Stephen T; George, Peter M; Slow, Sandy; Elmslie, Jane L; Florkowski, Christopher M; Lunt, Helen; Krebs, Jeremy D

2015-05-01

Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, one-carbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers. Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS). Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality = 0.52) and urine (index of individuality = 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and -35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to -80% in plasma). Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Monitoring MDMA metabolites in urban wastewater as novel biomarkers of consumption.

PubMed

González-Mariño, Iria; Zuccato, Ettore; Santos, Miquel M; Castiglioni, Sara

2017-05-15

Consumption of 3,4-methylendioxymethamphetamine (MDMA) has been always estimated by measuring the parent substance through chemical analysis of wastewater. However, this may result in an overestimation of the use if the substance is directly disposed in sinks or toilets. Using specific urinary metabolites may overcome this limitation. This study investigated for the first time the suitability of a panel of MDMA metabolites as biomarkers of consumption, considering the specific criteria recently proposed, i.e. being detectable and stable in wastewater, being excreted in a known percentage in urine, and having human excretion as the sole source. A new analytical method was developed and validated for the extraction and analysis of MDMA and three of its main metabolites in wastewater. 24-h composite raw wastewater samples from three European cities were analysed and MDMA use was back-calculated. Results from single MDMA loads, 4-hydroxy-3-methoxymethamphetamine (HMMA) loads and from the sum of MDMA, HMMA and 4-hydroxy-3-methoxyamphetamine (HMA) loads were in line with the well-known recreational use of this drug: consumption was higher during the weekend in all cities. HMMA and HMA turned out to be suitable biomarkers of consumption; however, concentrations measured in wastewater did not resemble the expected pharmacokinetic profiles, quite likely due to the very limited information available on excretion profiles. Different options were tested to back-calculate MDMA use, including the sum of MDMA and its metabolites, to balance the biases associated with each single substance. Nevertheless, additional pharmacokinetic studies are urgently needed in order to get more accurate excretion rates and, therefore, improve the estimates of MDMA use. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tissue Distribution and Urinary Excretion of Dimethylated Arsenic and Its Metabolites in Dimethylarsinic acid- or Arsenate-treated Rats - MCEARD

EPA Science Inventory

Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethy...

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

PubMed Central

Koulu, M; Scheinin, M; Kaarttinen, A; Kallio, J; Pyykkö, K; Vuorinen, J; Zimmer, R H

1989-01-01

1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A-type of the enzyme, were administered to eight young, healthy male volunteers in a double-blind, random-order, placebo-controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO-B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose-dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non-deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4-dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO-B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose-dependent and MAO-A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO-A inhibition in man. 4. Sympatho-adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose-dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged. PMID:2469451

The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation.

PubMed

Panzacchi, Simona; Mandrioli, Daniele; Manservisi, Fabiana; Bua, Luciano; Falcioni, Laura; Spinaci, Marcella; Galeati, Giovanna; Dinelli, Giovanni; Miglio, Rossella; Mantovani, Alberto; Lorenzetti, Stefano; Hu, Jianzhong; Chen, Jia; Perry, Melissa J; Landrigan, Philip J; Belpoggi, Fiorella

2018-05-29

Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine. We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA. Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA. Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.

Metabolites of hirsuteine and hirsutine, the major indole alkaloids of Uncaria rhynchophylla, in rats.

PubMed

Nakazawa, Takahiro; Banba, Koh-ichi; Hata, Kazumasa; Nihei, Yutaka; Hoshikawa, Ayumi; Ohsawa, Keisuke

2006-08-01

The metabolic fate of hirsuteine (HT) and hirsutine (HS), the major indole alkaloids of Uncaria rhynchophylla, was investigated using rats. On HPLC analysis, urine from rats orally administered HT were found to contain two metabolites (HT1 and HT2) together with unchanged HT. Similarly HS also was metabolized to two compounds (HS1 and HS2). Metabolite structures were determined to be 11-hydroxyhirsuteine-11-O-beta-D-glucuronide (HT1), 11-hydroxyhirsuteine (HT2), 11-hydroxyhirsutine-11-O-beta-D-glucuronide (HS1) and 11-hydroxyhirsutine (HS2), based on spectroscopic and chemical data. HT1 and HS1 were also detected in bile from rats administered HT and HS, respectively. Total cumulative urinary excretion within 72 h of oral administration was approximately 14% and 26% of the HT and HS doses, respectively, while total cumulative biliary excretion was 35% and 46%, respectively. HT and HS 11-hydroxylation were catalyzed by rat liver microsomes. This 11-hydroxylation activity was inhibited by addition of SKF-525A (a nonselective CYP inhibitor) or cimetidine (a CYP2C inhibitor). These results indicate that orally administered HT and HS are converted to 11-hydroxy metabolites in rats, and that the metabolites are predominantly excreted in bile rather than urine following glucuronidation. Furthermore, the results suggest that CYP2C enzymes are involved, at least in part, in the specific 11-hydroxylation of HT and HS.

2,5-Hexanedione excretion after occupational exposure to n-hexane.

PubMed Central

Ahonen, I; Schimberg, R W

1988-01-01

The urinary excretion of the n-hexane metabolite 2,5-hexanedione (HD) was determined in four shoe factory workers during four workingdays that were preceded by four free days and followed by two free days. The correlation between excretion of HD and the n-hexane concentrations in the workroom air was evaluated. The air concentrations of n-hexane and those of acetone, toluene, and other organic solvents were monitored with charcoal tubes. All the urine from each worker was collected at freely chosen intervals during the experimental period and the following two free days. The samples were analysed by gas chromatography. The relative excretion of HD increased as the exposure to n-hexane increased, although it seemed that HD accumulated progressively in the body at the highest n-hexane concentrations and at higher total solvent concentrations. Images PMID:3342196

Variability of urinary salt excretion estimated by spot urine in treated hypertensive patients.

PubMed

Arakawa, Kimika; Sakaki, Minako; Sakata, Satoko; Oniki, Hideyuki; Tominaga, Mitsuhiro; Tsuchihashi, Takuya

2015-01-01

Among the several methods used to assess salt intake, estimating 24 h urinary salt excretion by spot urine seems appropriate for clinical practice. In this study, we investigated variability in urinary salt excretion using spot urine in hypertensive outpatients. Participants included 200 hypertensive patients who underwent spot urinary salt excretion at least three times during the observation period. Mean urinary salt excretion and the coefficient of the variation were 8.62 ± 1.96 g/day and 19.0 ± 10.2%, respectively. In the analysis of participants who underwent assessment of urinary salt excretion at least eight times (n = 54), a significant reduction in mean urinary salt excretion was found at the 5th measurement. On the contrary, the coefficient of the variation of urinary salt excretion continued to increase until the 5th measurement, and became stable thereafter. Mean urinary salt excretion was positively correlated with mean clinic diastolic blood pressure (r = 0.27, p < 0.05). Clinic diastolic blood pressure in the high urinary salt excretion group (≥ 10 g/day) was significantly higher than that of the low group (76.2 ± 7.5 vs 73.4 ± 8.3 mmHg, p < 0.05). Mean urinary salt excretion in summer was significantly lower than that of the other seasons (7.75 ± 1.94 vs 9.09 ± 2.68 (spring), 8.72 ± 2.12 (autumn), 8.92 ± 2.17 (winter) g/day, p < 0.01). In conclusion, repeated measurements of urinary salt excretion using spot urine are required to assess daily salt intake of hypertensive patients.

Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans.

PubMed

Mullen, William; Borges, Gina; Donovan, Jennifer L; Edwards, Christine A; Serafini, Mauro; Lean, Michael E J; Crozier, Alan

2009-06-01

Cocoa drinks containing flavan-3-ols are associated with many health benefits, and conflicting evidence exists as to whether milk adversely affects the bioavailability of flavan-3-ols. The objective was to determine the effect of milk on the bioavailability of cocoa flavan-3-ol metabolites. Nine human volunteers followed a low-flavonoid diet for 2 d before drinking 250 mL of a cocoa beverage, made with water or milk, that contained 45 micromol (-)-epicatechin and (-)-catechin. Plasma and urine samples were collected for 24 h, and flavan-3-ol metabolites were analyzed by HPLC with photodiode array and mass spectrometric detection. Milk affected neither gastric emptying nor the transit time through the small intestine. Two flavan-3-ol metabolites were detected in plasma and 4 in urine. Milk had only minor effects on the plasma pharmacokinetics of an (epi)catechin-O-sulfate and had no effect on an O-methyl-(epi)catechin-O-sulfate. However, milk significantly lowered the excretion of 4 urinary flavan-3-ol metabolites from 18.3% to 10.5% of the ingested dose (P = 0.016). Studies that showed protective effects of cocoa and those that showed no effect of milk on bioavailability used products that have a much higher flavan-3-ol content than does the commercial cocoa used in the present study. Most studies of the protective effects of cocoa have used drinks with a very high flavan-3-ol content. Whether similar protective effects are associated with the consumption of many commercial chocolate and cocoa products containing substantially lower amounts of flavan-3-ols, especially when absorption at lower doses is obstructed by milk, remains to be determined.

Influence of delivery mode on the urinary excretion of nandrolone metabolites.

PubMed

Watson, Phillip; Houghton, Ed; Grace, Philip B; Judkins, Catherine; Dunster, Paula M; Maughan, Ronald J

2010-04-01

This study examined the influence of a supplement matrix on the excretion pattern of nandrolone metabolites in response to ingestion of a trace amount of 19-norandrostenedione. Ten male and nine female volunteers (mean ± SD: age = 26 ± 3 yr, height = 1.71 ± 0.09 m, body mass = 70.9 ± 13.2 kg) were recruited. On two occasions, subjects entered the laboratory in the morning after an overnight fast. After an initial urine collection, subjects ingested either 500 mL of plain water or a commercially available energy bar; 10 µg of 19-norandrostenedione was added to each. The volume of each urine sample passed during the next 24 h was measured, and an aliquot was retained for analysis. All samples were analyzed for the metabolites 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) by gas chromatography-mass spectrometry. The total volume of urine passed was higher in the water trial (2.10 ± 0.52 L) than in the bar trial (1.85 ± 0.55 L; P = 0.040). Baseline urinary 19-NA concentrations were all below the limit of quantification for the assay. Peak urinary 19-NA was lower (P = 0.002) in the water trial (4.80 ± 2.84 ng·mL(-1)) than in the bar trial (8.46 ± 4.44 ng·mL(-1)). The time elapsed between ingestion of the supplement and the peak urinary 19-NA concentration was longer (P = 0.023) on the bar trial (4.6 ± 2.4 h) than on the water trial (2.8 ± 1.9 h). There was no difference in the total recovery of 19-NA + 19-NE between the liquid and solid supplements (water 30 ± 10%; bar 28 ± 12%; P < 0.140). Peak 19-NA concentrations were higher, and occurred later, when the 19-norandrostenedione was added to a solid supplement. This may be due to a slower rate of absorption and/or a reduced diuresis, resulting in a longer period for the metabolites to accumulate in the urine.

Assessment of serum pharmacokinetics and urinary excretion of albendazole and its metabolites in human volunteers.

PubMed

Ceballos, Laura; Krolewiecki, Alejandro; Juárez, Marisa; Moreno, Laura; Schaer, Fabian; Alvarez, Luis I; Cimino, Rubén; Walson, Judd; Lanusse, Carlos E

2018-01-01

Soil Transmitted Helminth (STH) infections negatively impact physical and mental development in human populations. Current WHO guidelines recommend morbidity control of these infections through mass drug administration (MDA) using albendazole (ABZ) or mebendazole. Despite major reductions in STH associated morbidity globally, not all programs have demonstrated the expected impact on prevalence of parasite infections. These therapeutic failures may be related to poor programmatic coverage, suboptimal adherence or the exposure of parasites to sub-therapeutic drug concentrations. As part of the DeWorm3 project, we sought to characterize the serum disposition kinetics and pattern of urinary excretion of ABZ and its main metabolites ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2) in humans, and the assessment of the duration and optimal time point where ABZ and/or its metabolites can be measured in urine as an indirect assessment of an individual's adherence to treatment. Consecutive venous blood and urine samples were collected from eight (8) human volunteers up to 72 h post-ABZ oral administration. ABZ/metabolites were quantified by HPLC. The ABZSO metabolite was the main analyte recovered both in serum and urine. ABZSO Cmax in serum was 1.20 ± 0.44 μg/mL, reached at 4.75 h post-treatment. In urine, ABZSO Cmax was 3.24 ± 1.51 μg/mL reached at 6.50 h post-ABZ administration. Pharmacokinetic data obtained for ABZ metabolites in serum and urine, including the recovery of the ABZ sulphoxide derivative up to 72 h in both matrixes and the recovery of the amino-ABZ sulphone metabolite in urine samples, are suggesting the possibility of developing a urine based method to assess compliance to ABZ treatment. Such an assay may be useful to optimize ABZ use in human patients. ClinicalTrials.gov NCT03192449.

Evaluation of 1-hydroxypyrene as a biological marker of industrial exposure to polycyclic aromatic hydrocarbons

NASA Astrophysics Data System (ADS)

Calderon, Francisco M.

1993-03-01

One hundred twenty-two workers (sixteen from a coke production plant and 106 from a graphite electrode manufacturing plant) agreed to participate in this study evaluating the relationship between exposure to polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-HOP), the main metabolite of pyrene. The results show that the concentration of pyrene in air is highly correlated with total PAHs (r equals 0.83, P < 0.0001). The correlation coefficient between pyrene in air and 1-HOP is (r equals 0.69, P < 0.0001) and between 1-HOP and total PAHs is (r equals 0.77, P < 0.0001). The biological half life of the 1-HOP was determined (18 hrs) and the noninterference of smoking habits in relation to 1-HOP urinary excretion was established, concluding that 1-HOP is a suitable bioindicator of the occupational exposure to PAHs.

Estimation of the percutaneous absorption of styrene in an industrial situation.

PubMed

Limasset, J C; Simon, P; Poirot, P; Subra, I; Grzebyk, M

1999-01-01

This field study was designed to compare the level of styrene absorbed percutaneously with that absorbed by inhalation in a real situation in the fiberglass-reinforced polyester industry. The study protocol consisted of comparisons of the patterns of urinary excretion of styrene metabolites by four groups of workers, all of whom performed the same task at the same time in the same workshop but wore the following different protective equipment: total protection with an insulating suit and mask, respiratory equipment only, percutaneous protection only, and no protection. The urinary excretion level of the group with total protection did not significantly differ from that of the group with respiratory protection only. Precutaneous absorption is not a particularly important pathway for styrene absorption during stratification work in the polyester industry. Completely insulating personal protective equipment provides no greater level of protection than does a respirator at positive pressure alone.

Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man.

PubMed

Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R; Galli, M

1976-04-20

Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.

Semen quality and insulin-like factor 3: Associations with urinary and seminal levels of phthalate metabolites in adult males.

PubMed

Chang, Wei-Hsiang; Wu, Meng-Hsing; Pan, Hsien-An; Guo, Pao-Lin; Lee, Ching-Chang

2017-04-01

Certain phthalates have adverse effects on male reproductive functions in animals, and potentially affect human testicular function and spermatogenesis, but little is known about the active mechanisms. We measured the urinary and seminal phthalate metabolites and explored their associations on insulin-like factor 3 (INSL3) and semen quality. Urine, blood, and semen samples were collected from the male partners of subfertile (n = 253) and fertile (n = 37) couples in a reproductive center in southern Taiwan. INSL3, reproductive hormones, semen-quality, and 11 phthalate metabolites in urine and semen were measured. There were significant correlations in the distribution pattern of metabolites, such as the relative contribution of low or high molecular weight phthalate metabolites. The significantly monotonic trends in semen volume, sperm concentration and motility were associated with increasing quartiles of INSL3 (all p-trend < 0.001). In adjusted regression models, increases in urinary phthalate metabolites levels were adversely associated with sperm concentration (monobenzyl phthalate [MBzP], mono-2-ethylhexyl phthalate [MEHP] and MEHP%), motility (MBzP and MEHP) and INSL3 (MBzP, MEHP and MEHP%) (all p < 0.01). Higher seminal phthalate metabolite levels were associated with decreases in sperm concentration (MEHP and mono-2-ethyl-5-hydroxyhexyl phthalate), motility (mono-ethyl phthalate [MEP] and di-(2-ethylhexyl) phthalate [DEHP] metabolites), normal morphology (MEP), and INSL3 (monomethyl phthalate and MEP) (all p < 0.05). Our data suggest that INSL3 secretion, reproductive hormone balance, and sperm production and quality might be simultaneously adversely affected for individuals excreting increasing levels of phthalates metabolites (especially di-ethyl phthalate, butylbenzyl phthalate, and DEHP) in urine and semen samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of dose on the bioavailability of coffee chlorogenic acids in humans.

PubMed

Stalmach, Angélique; Williamson, Gary; Crozier, Alan

2014-08-01

Single servings of coffee beverage containing low (412 μmol), medium (635 μmol) and high (795 μmol) amounts of chlorogenic acids were administered to eleven healthy volunteers in a double-blind randomised controlled trial. Analysis of plasma and urine collected for 24 h revealed the presence of 12 metabolites in plasma and 16 metabolites in urine, principally in the form of sulphates, and to a lesser extent glucuronides of caffeic, ferulic, dihydrocaffeic and dihydroferulic acids, as well as intact feruloylquinic and caffeoylquinic acids, and sulphated caffeoylquinic acid lactones. Median values of peak plasma concentrations after increasing doses of chlorogenic acids were 1088, 1526 and 1352 nM. In urine the median amounts of metabolites excreted after 24 h following consumption of the three coffees were 101, 160 and 125 μmol, accounting for 24%, 25% and 16% of the doses ingested. Peak plasma concentration and urinary excretion values showed trends towards a reduced bioavailability of chlorogenic acids associated with the highest dose ingested, when expressed as percentages of intake. Potential biomarkers of coffee intake were identified as feruloylquinic acids and sulphated caffeoylquinic acid lactones in plasma and urine with positive moderate to strong coefficients of determination for peak plasma concentrations (0.60-0.81) and amounts excreted in urine (0.36-0.73) (P < 0.05).

Influence of body mass index status on urinary creatinine and specific gravity for epidemiological study of children.

PubMed

Wang, Bin; Tang, Chuanxi; Wang, Hexing; Zhou, Wei; Chen, Yue; Zhou, Ying; Jiang, Qingwu

2015-11-01

In epidemiological studies, urinary biomonitoring is a valid approach to assess the association between environmental chemical exposure and children's health. Many clinical biomarkers (e.g., endogenous metabolites) are also based on analysis of urine. Considering the variability in urinary output, urinary concentrations of chemicals are commonly adjusted by creatinine and specific gravity (SG). However, there is a lack of systematic evaluation of their appropriateness for children. Furthermore, urinary SG and creatinine excretion could be influenced by body mass index (BMI), but the effect of BMI status on the two correction factors is unknown. We measured SG and creatinine concentrations of repeated first morning urine samples collected from 243 primary school children (8-11 years) over 5 consecutive weekdays. Urinary SG presented a higher temporal consistency compared with creatinine. Urinary SG was associated with sex (p < 0.001), whereas sex (p =0.034) and BMI (p = 00.008) were associated with urinary creatinine levels. Inter-day collection time was not associated with SG or creatinine after excluding the effect of Monday as a confounder. When stratified by BMI status, none of the factors were associated with creatinine among the overweight and obese children. Generally, SG is preferable for correcting the variability in urinary output for children although creatinine correction may also perform well in overweight and obese children. SG correction is recommended for epidemiological exposure analysis in children based on urinary levels of exogenous or endogenous metabolites.

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease.

PubMed

Juretzko, Annett; Steinbach, Antje; Hannemann, Anke; Endlich, Karlhans; Endlich, Nicole; Friedrich, Nele; Lendeckel, Uwe; Stracke, Sylvia; Rettig, Rainer

2017-01-01

Several studies sought to identify new biomarkers for chronic kidney disease (CKD). As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR). We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC) curves, spearman correlation coefficients and linear regression models were calculated. Urinary angiotensinogen [2,511 (196-31,909) vs. 18.6 (8.3-44.0) pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155) vs. 0.069 (0.045-0.148) pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01) and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01) were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may convey additional information beyond that provided by albuminuria. © 2017 The Author(s)Published by S. Karger AG, Basel.

[Bemetil pharmacokinetics in an experiment on rats].

PubMed

Boĭko, S S; Bobkov, Iu G; Zherdev, V P; Dvorianinov, A A

1987-01-01

Pharmacokinetics of bemetil (2-ethyl-mercaptobenzimidazole), a representative of the group of actoprotectors, was studied at intravenous and intragastric administration during the experiment on rats by using gas-liquid chromatography. It was found that at intragastric administration the drug rapidly appeared in the systemic circulation, reached the maximal concentration in one hour; the character of bemetil elimination from the blood was biexponential at both routes of administration. The two-compartment model was used for calculation of the main pharmacokinetic constants and bioavailability. The analysis of the experimental findings on urinary excretion of bemetil made it possible to conclude that little amount of the drug (0.56%) is excreted in the urine in the unchanged form; most amount of bemetil is excreted in the form of metabolites and in the bound state.

Predictors and long-term reproducibility of urinary phthalate metabolites in middle-aged men and women living in urban Shanghai

PubMed Central

Starling, Anne P.; Engel, Lawrence S.; Calafat, Antonia M.; Koutros, Stella; Satagopan, Jaya M.; Yang, Gong; Matthews, Charles E.; Cai, Qiuyin; Buckley, Jessie P.; Ji, Bu-Tian; Cai, Hui; Chow, Wong-Ho; Zheng, Wei; Gao, Yu-Tang; Rothman, Nathaniel; Xiang, Yong-Bing; Shu, Xiao-Ou

2015-01-01

Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤ 0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl)phthalate, had a Spearman rank correlation coefficient ≥ 0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population. PMID:26255822

Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo-controlled, crossover trial.

PubMed

Hollands, Wendy J; Hart, David J; Dainty, Jack R; Hasselwander, Oliver; Tiihonen, Kirsti; Wood, Richard; Kroon, Paul A

2013-07-01

Flavanol-rich foods are known to exert beneficial effects on cardiovascular health. The biological effects depend on bioavailability of flavanols which may be influenced by food matrix and dose ingested. We compared the bioavailability and dose-response of epicatechin from whole apple and an epicatechin-rich extract, and the effects on plasma and urinary nitric oxide (NO) metabolites. In a randomized, placebo-controlled, crossover trial, subjects consumed drinks containing 70 and 140 mg epicatechin from an apple extract and an apple puree containing 70 mg epicatechin. Blood and urine samples were collected for 24 h post ingestion. Maximum plasma concentration, AUC(0-24 h) , absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p < 0.05). Time to maximum plasma concentration was significantly later for the puree compared with the drinks (p < 0.01). Epicatechin bioavailability was >2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). Excretion of NO metabolites was higher for all test products compared with placebo, which was significant for the high dose drink (p = 0.016). Oral bioavailability of apple epicatechin increases at higher doses, is reduced by whole apple matrix and has the potential to increase NO bioavailability. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolism and pharmacokinetics of selected halon replacement candidates.

PubMed

Dodd, D E; Brashear, W T; Vinegar, A

1993-05-01

Metabolism studies were conducted using Fischer 344 and Sprague-Dawley rats following inhalation exposure to 1.0% (v/v) air atmospheres of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123), 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), 1-chloro-1,1-difluoroethane (HCFC-142b), bromochlorodifluoromethane (Halon 1211), and perfluorohexane (PFH) for 2 h. There were no remarkable differences in results between the two strains of rats. Animals exposed to HCFC-123 or HCFC-124 excreted trifluoroacetic acid in their urine. Urinary fluoride concentrations were increased in rats exposed to HCFC-124, and urinary bromide levels were increased in rats exposed to Halon 1211. Small quantities of volatile metabolites 2-chloro-1,1,1-trifluoroethane (HCFC-133a) and 2-chloro-1,1-difluoroethylene were observed in the livers of rats exposed to HCFC-123. Rats exposed to HCFC-142b excreted chlorodifluoroacetic acid in their urine; no volatile metabolites were detected in tissue samples. For PFH studies, no metabolites were detected in the urine or tissues of exposed animals. These results are consistent with proposed oxidative and reductive pathways of metabolism for these chemicals. Pharmacokinetic studies were carried out in rats exposed by inhalation to 1.0%, 0.1%, or 0.01% of HCFC-123. Following exposure, blood concentrations of HCFC-123 fell sharply, whereas trifluoroacetic acid levels rose for approx. 5 h and then declined gradually. Using a physiologically based pharmacokinetic model, saturation of HCFC-123 metabolism was estimated to occur at approx. 0.2% (2000 ppm) HCFC-123.

Disposition and metabolism of 2-bromo-4,6-dinitroaniline in the male F344 rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chopade, H.M.; Matthews, H.B.

1986-01-01

The disposition of (/sup 14/C)-2-bromo-4,6-dinitroaniline (BDNA) was studied in male F344 rats following oral or intravenous (iv) administration. The gastrointestinal absorption of BDNA was nearly complete and was not affected by dose in the range (10-100 ..mu..mol/kg body weight) studied. Following either oral or iv administration, BDNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue. Clearance of (/sup 14/C)BDNA-derived radioactivity from various tissues was rapid and was best described by two-component decay curves. The whole-body half-life of BDNA was approximately 7 h. Within 72 h, clearance of (/sup 14/C)BDNA-derived radioactivity from the bodymore » was 98% complete. (/sup 14/C)BDNA was rapidly cleared by metabolism to 13 metabolites, which were excreted in urine (62%) and feces (33%). Most (66%) of the urinary radioactivity was excreted in the form of sulfate conjugates of two metabolites of BDNA; excretion of unmetabolized BDNA was minimal (less than 2%). Biliary excretion of (/sup 14/C)BDNA was significant; however, some of this BDNA-derived radioactivity underwent enterohepatic circulation and was subsequently excreted in urine. Results of this study indicate that, if metabolism is a detoxification process, the rapid metabolism and excretion of this compound should minimize the likelihood of chronic toxicity from repeated exposure to BDNA beyond that predicted by data from acute or short-term exposures.« less

Almond (Prunus dulcis (Mill.) D.A. Webb) polyphenols: from chemical characterization to targeted analysis of phenolic metabolites in humans.

PubMed

Bartolomé, Begoña; Monagas, María; Garrido, Ignacio; Gómez-Cordovés, Carmen; Martín-Alvarez, Pedro J; Lebrón-Aguilar, Rosa; Urpí-Sardà, Mireia; Llorach, Rafael; Andrés-Lacueva, Cristina

2010-09-01

In this paper, a survey of our studies on almond polyphenols including their chemical characterization and further bioavailability in humans is reported. Combination of analytical techniques (LC-DAD/fluorescence, LC/ESI-MS and MALDI-TOF-MS) allowed us, for the first time, the identification of A- and B-type procyanidin, propelargonidin and prodelphinidin polymers in almond skins. Glucuronide, O-methyl glucuronide, sulfate and O-methyl sulfate derivatives of (epi)catechin, as well as the glucuronide conjugates of naringenin and isorhamnetin, and sulfate conjugates of isorhamnetin, together with conjugates of hydroxyphenylvalerolactones were detected in plasma and urine samples after the intake of almond skin polyphenols. In addition, numerous microbial-derived metabolites, including hydroxyphenylpropionic, hydroxyphenylacetic, hydroxycinnamic, hydroxybenzoic and hydroxyhippuric acids were also identified. Depending of the type of metabolite, maximum urinary excretion was attained at different time in comparison to the control group in the course of the 24-h period of urine excretion, allowing us to establish the onset of microbial metabolism. 2010 Elsevier Inc. All rights reserved.

LY3127760, a Selective Prostaglandin E4 (EP4) Receptor Antagonist, and Celecoxib: A Comparison of Pharmacological Profiles

PubMed Central

Smith, Claire; Hu, Leijun; Coutant, David E.; Whitehurst, Kelly; Phipps, Krista; McNearney, Terry Ann; Yang, Xiao; Ackermann, Bradley; Pottanat, Thomas; Landschulz, William

2017-01-01

Abstract Safety, tolerability, and pharmacology profiles of LY3127760, an EP4 antagonist, were explored in healthy subjects in a subject/investigator‐blind, parallel‐group, multiple‐ascending dose study. Cohorts consisted of 13 patients randomized to LY3127760, celecoxib (400 mg), or placebo (9:2:2 ratio) for 28 days. LY3127760 was well tolerated; the most commonly observed adverse events were gastrointestinal, similar to celecoxib. LY3127760 increased release of ex vivo tumor necrosis factor alpha after lipopolysaccharide/prostaglandin E2 stimulation when compared with placebo, suggesting a dose‐dependent blockade of the EP4 receptor. Compared with placebo, 24‐h urinary excretion of prostaglandin E metabolite was modestly increased; prostacyclin metabolite was inhibited; and thromboxane A2 metabolite was unchanged. Effects on sodium and potassium excretion were similar to those of celecoxib. We conclude that LY3127760 demonstrated similar effects on prostacyclin synthesis and renal sodium retention as celecoxib. These data support exploration of LY3127760 at daily doses of 60 mg to 600 mg in phase II trials. This trial's registration number: NCT01968070. PMID:28857461

Biotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.

2013-05-01

trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is negative in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected formore » 48 h after the end of the exposure. Study specimens were analyzed for metabolites using {sup 19}F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t{sub 1/2} < 6 h) and the extent of biotransformation of trans-HCFO-1233zd was determined as approximately 0.01% of received dose in rabbits and approximately 0.002% in rats. trans-HCFO-1233zd undergoes both oxidative biotransformation and glutathione conjugation at very low rates. The low extent of biotransformation and the rapid excretion of metabolites formed are consistent with the very low potential for toxicity of trans-HCFO-1233zd in mammals. - Highlights: ► No lethality and clinical signs were observed. ► Glutathione S-transferase and cytochrome P-450 dependent biotransformation in vivo. ► Low biotransformation (< 0.01%) and fast metabolite excretion (t{sub 1/2} < 6 h). ► Glutathione adduct as predominant in vitro metabolite in all tested species. ► Toxic metabolites could not be detected in any great extent.« less

Urinary Metabolites Associated with Blood Pressure on a Low- or High-Sodium Diet

PubMed Central

Cheng, Yuan; Song, Haiying; Pan, Xiaoqing; Xue, Hong; Wan, Yifei; Wang, Tao; Tian, Zhongmin; Hou, Entai; Lanza, Ian R.; Liu, Pengyuan; Liu, Yong; Laud, Purushottam W.; Usa, Kristie; He, Yongcheng; Liang, Mingyu

2018-01-01

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically. Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day). Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle. The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats. Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex. Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of β-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure. The differences in homocysteine levels between low- and high-sodium intakes were significantly associated with the differences in diastolic blood pressure. These associations were significant with or without considering demographic factors. Treatment with β-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats. Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension. PMID:29556335

Urinary Metabolites Associated with Blood Pressure on a Low- or High-Sodium Diet.

PubMed

Cheng, Yuan; Song, Haiying; Pan, Xiaoqing; Xue, Hong; Wan, Yifei; Wang, Tao; Tian, Zhongmin; Hou, Entai; Lanza, Ian R; Liu, Pengyuan; Liu, Yong; Laud, Purushottam W; Usa, Kristie; He, Yongcheng; Liang, Mingyu

2018-01-01

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically. Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day). Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle. The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats. Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex. Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of β-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure. The differences in homocysteine levels between low- and high-sodium intakes were significantly associated with the differences in diastolic blood pressure. These associations were significant with or without considering demographic factors. Treatment with β-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats. Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension.

Toxicokinetics of 1,2-diethylbenzene in male Sprague-Dawley rats-part 1: excretion and metabolism of [(14)C]1,2-diethylbenzene.

PubMed

Payan, J P; Beydon, D; Cossec, B; Ensminger, A; Fabry, J P; Ferrari, E

1999-12-01

The excretion and metabolism of neurotoxic 1,2-diethylbenzene (1, 2-DEB) was studied in male Sprague-Dawley rats after i.v. (1 mg/kg) or oral (1 or 100 mg/kg) administration of 1,2-diethyl[U-(14)C]benzene ([(14)C]1,2-DEB). Whatever the treatment, radioactivity was mainly excreted in urine (65-76% of the dose) and to a lower extent in feces (15-23% of the dose), or via exhaled air (3-5% of the dose). However, experiments with rats fitted with a biliary cannula demonstrated that about 52 to 64% of the administered doses (1 or 100 mg/kg) were initially excreted in bile. Biliary metabolites were extensively reabsorbed from the gut and ultimately excreted in urine after several enterohepatic circulations. Insignificant amounts of unchanged 1,2-DEB were recovered in the different excreta (urine, bile, and feces). As reported previously, presence of 1-(2'-ethylphenyl)ethanol (EPE) was confirmed in urine and demonstrated in bile and feces. The two main [(14)C]1,2-DEB metabolites accounted for 57 to 79% of urinary and biliary radioactivity, respectively. Beta-Glucuronidase hydrolysis and electron impact mass spectra results strongly supported their glucuronide structure. Additionally, these two main metabolites were thought to be the glucuronide conjugates of the two potential enantiomers of EPE. The results indicate that the main initial conversion step of the primary metabolic pathway of 1,2-DEB appears to be the hydroxylation of the alpha-carbon atom of the side chain. The presence of two glucuronide conjugates of EPE in the urine in a ratio different from one suggests that the metabolic conversion of 1, 2-DEB is under stereochemical control.

Quantitative determination of the anti-tumor agent tasquinimod in human urine by liquid chromatography-tandem mass spectrometry.

PubMed

van de Merbel, Nico C; Walland, Peter; Tiensuu, Mikael; Sennbro, Carl J

2014-06-15

Tasquinimod is an anti-tumor drug that is currently in clinical development for the treatment of solid cancers. After oral administration, tasquinimod and a number of its metabolites are excreted in the urine. The quantitative determination of tasquinimod in urine is challenging because of the required sensitivity (down to 0.1nM or 40pg/mL), the highly variable nature of this biological matrix and the presence of potentially unstable metabolites, which may convert back to the parent drug. In this article, an LC-MS/MS method is described for the determination of tasquinimod in human urine in the concentration range 0.1-200nM. Liquid-liquid extraction with n-chlorobutane was used to extract tasquinimod from 100μL human urine and to remove interfering endogenous urinary constituents. Reversed-phase liquid chromatography coupled to a triple quadrupole mass spectrometer equipped with an ESI source was used for quantification of tasquinimod in a 2.5-min run. A stable-isotope labeled internal standard was used for response normalization. The intra- and inter-day coefficients of variation (precision) as well as the bias (accuracy) of the method were below 7%. Although considerable conversion of conjugated tasquinimod metabolites back to parent drug was observed when incurred samples were stored at 37°C for a prolonged time, tasquinimod as well as its metabolites were sufficiently stable under all relevant sampling, storage and analysis conditions. The method was successfully applied to determine the urinary excretion of tasquinimod in healthy volunteers and patients with renal impairment after a 0.5-mg oral dose. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of low dose rate on metabolomic response to radiation in mice

PubMed Central

Goudarzi, Maryam; Mak, Tytus D.; Chen, Congju; Smilenov, Lubomir B.; Brenner, David J.

2014-01-01

Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual's exposure in a radiobiological event and thus would have utility for both triage and injury assessment. PMID:25047638

The tomato sauce making process affects the bioaccessibility and bioavailability of tomato phenolics: a pharmacokinetic study.

PubMed

Martínez-Huélamo, Miriam; Tulipani, Sara; Estruch, Ramón; Escribano, Elvira; Illán, Montserrat; Corella, Dolores; Lamuela-Raventós, Rosa M

2015-04-15

Tomato sauce is the most commonly consumed processed tomato product worldwide, but very little is known about how the manufacturing process may affect the phenolic composition and bioavailability after consumption. In a prospective randomised, cross-over intervention study, we analysed the plasma and urinary levels of tomato phenolic compounds and their metabolites after acute consumption of raw tomatoes and tomato sauce, enriched or not with refined olive oil during production. Respectively, eleven and four phenolic metabolites were found in urine and plasma samples. The plasma concentration and urinary excretion of naringenin glucuronide were both significantly higher after the consumption of tomato sauce than raw tomatoes. The results suggest that the mechanical and thermal treatments during tomato sauce manufacture may help to deliver these potentially bioactive phenolics from the food matrix more effectively than the addition of an oil component, thus increasing their bioavailability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metabolism of norethisterone in the greyhound.

PubMed

Biddle, S T B; O'Donnell, A; Houghton, E; Creaser, C S

2013-10-30

Norethisterone has been used as a successful oral contraceptive in humans for many years. It was recently permitted for use as an oestrus suppressant in racing greyhounds. To monitor the use of norethisterone as part of a routine drug surveillance programme, knowledge of its metabolism was required to enable detection. Gas chromatography/mass spectrometry and selective derivatisation techniques have been used to identify urinary metabolites of norethisterone following oral administration to the greyhound. Metabolites were extracted using solid-phase and liquid-liquid extraction techniques. Several metabolites were identified, including reduced, mono-, di- and trihydroxylated steroids. The major metabolites observed were 17α-ethynyl-5β-estrane-3α,17β-diol, 17α-ethynyl-5α-estrane-3β,17β-diol, three 17α-ethynylestranetriol stereoisomers and two 17α-ethynylestranetetrol stereoisomers. The major metabolites were predominantly excreted as glucuronic acid conjugates and detection of the administration of norethisterone was possible for up to 8 days post-dose using the methods described. The nandrolone metabolites, 19-norepiandrosterone, estranediol and 19-noretiocholanolone, were also identified in the post-administration samples collected up to 8 h after dosing the treated animals. The urinary metabolites identified in this study have further increased the knowledge of steroid metabolism in the greyhound, providing information to support routine drug testing programmes for greyhound racing. Copyright © 2013 John Wiley & Sons, Ltd.

Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.

PubMed

Clarke, Michael W; Ward, Natalie C; Wu, Jason H Y; Hodgson, Jonathan M; Puddey, Ian B; Croft, Kevin D

2006-01-01

Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P < 0.001) in the mixed tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum alpha-tocopherol and serum and cellular gamma-tocopherol. Changes in serum tocopherol closely reflect changes in cellular concentrations of tocopherols after supplementation.

Association of urinary calcium excretion with serum calcium and vitamin D levels.

PubMed

Rathod, Anita; Bonny, Olivier; Guessous, Idris; Suter, Paolo M; Conen, David; Erne, Paul; Binet, Isabelle; Gabutti, Luca; Gallino, Augusto; Muggli, Franco; Hayoz, Daniel; Péchère-Bertschi, Antoinette; Paccaud, Fred; Burnier, Michel; Bochud, Murielle

2015-03-06

Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15-95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein-corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, -0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, -0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion. Copyright © 2015 by the American Society of Nephrology.

Deriving Biomonitoring Equivalents for selected E- and P-series glycol ethers for public health risk assessment.

PubMed

Poet, Torka; Ball, Nicholas; Hays, Sean M

2016-01-01

Glycol ethers are a widely used class of solvents that may lead to both workplace and general population exposures. Biomonitoring studies are available that have quantified glycol ethers or their metabolites in blood and/or urine amongst exposed populations. These biomonitoring levels indicate exposures to the glycol ethers, but do not by themselves indicate a health hazard risk. Biomonitoring Equivalents (BEs) have been created to provide the ability to interpret human biomonitoring data in a public health risk context. The BE is defined as the concentration of a chemical or metabolite in a biological fluid (blood or urine) that is consistent with exposures at a regulatory derived safe exposure limit, such as a tolerable daily intake (TDI). In this exercise, we derived BEs for general population exposures for selected E- and P-series glycol ethers based on their respective derived no effect levels (DNELs). Selected DNELs have been derived as part of respective Registration, Evaluation, Authorisation and Regulation of Chemicals (REACh) regulation dossiers in the EU. The BEs derived here are unique in the sense that they are the first BEs derived for urinary excretion of compounds following inhalation exposures. The urinary mass excretion fractions (Fue) of the acetic acid metabolites for the E-series GEs range from approximately 0.2 to 0.7. The Fues for the excretion of the parent P-series GEs range from approximately 0.1 to 0.2, with the exception of propylene glycol methyl ether and its acetate (Fue = 0.004). Despite the narrow range of Fues, the BEs exhibit a larger range, resulting from the larger range in DNELs across GEs. The BEs derived here can be used to interpret human biomonitoring data for inhalation exposures to GEs amongst the general population. Copyright © 2015 Elsevier GmbH. All rights reserved.

Effects of high-intensity exercises on 13C-nandrolone excretion in trained athletes.

PubMed

Baume, Norbert; Avois, Lidia; Sottas, Pierre-Edouard; Dvorak, Jiri; Cauderay, Michel; Mangin, Patrice; Saugy, Martial

2005-05-01

Nandrolone is an anabolic steroid widely used in several sports. The numerous nandrolone positive cases in the recent years (International Olympic Committee statistics) led to several studies in the antidoping field. Nevertheless, essential questions pertaining to nandrolone endogenous production, the effects of physical exercise on the excretion of nandrolone metabolites, and contamination from nutritional supplements must still be addressed. The purpose of this study was to evaluate the influence of exhaustive exercises on 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) urinary excretion rates after administration of labeled nandrolone. A total of 34 healthy male Caucasian volunteers from the Institute of Sports Sciences and Physical Education (University of Lausanne) applied to participate in the study. All subjects were free from any physical drug addiction and were instructed strictly to avoid any nutritional supplement or steroid before and during the study. The participants were randomly dispatched in 2 groups in a double-blind way: a placebo group and a group treated with C-labeled nandrolone. The urinary concentrations of the 2 main nandrolone metabolites, 19-NA and 19-NE, were measured using gas chromatography coupled with mass spectrometry. In addition, clinical parameters such as creatinine, total protein, and beta2-microglobuline levels were determined using immunologic assays. After an oral ingestion of a 25 mg 3,4-C2-nandrolone dose, followed by a second identical dose 24 hours later, 19-NA and 19-NE could be detected in the urine for a period of 6 days after the initial intake. Despite several interesting observations, the measurements were very scattered and did not appear to be significantly influenced by exercise sessions in the athlete population. The results of this study suggest that physical exercise cannot be considered as a reliable parameter that systematically affects nandrolone metabolite concentrations in the urine.

Formation and disposition of the minor metabolites of acetaminophen in the hamster.

PubMed

Gemborys, M W; Mudge, G H

1981-01-01

The urinary metabolites of acetaminophen and N-hydroxyacetaminophen were studied in the hamster over a wide dose range and with pretreatments designed to modify drug metabolism. Attention was focused on the origin and disposition of the minor metabolites. The sum of the 3-thio adducts, rather than just the 3-mercapturic adduct, is considered the better index of the formation of the reactive immediate precursor, presumably N-acetyl-p-benzoquinoneimine. At low dosage this amounts to 33% of the administered dose in this species. There is a major contribution from the 3-methylthio adduct, the magnitude of which has not been previously recognized. The 3-methylthio and the 3-methylsulfoxide derivates of acetaminophen are secondarily derived from the 3-glutathione adduct within the enterohepatic circulation, as indicated by their late appearance in the urine, the effect of common bile duct ligation and the metabolism of the minor metabolites when they themselves are administered. Following the administration of N-hydroxyacetaminophen this was excreted in the urine along with its phenolic conjugates, but no urinary N-hydroxyacetaminophen was detectable after the administration of acetaminophen itself. Of particular interest to the pathogenesis of analgesic nephropathy was the detection in the urine of small amounts of p-aminophenol, a known nephrotoxic agent, following dosage with acetaminophen. This metabolite has not been previously detected.

Harnessing the Power of Cruciferous Vegetables: Developing a Biomarker for Brassica Vegetable Consumption Using Urinary 3,3'-Diindolylmethane.

PubMed

Fujioka, Naomi; Ransom, Benjamin W; Carmella, Steven G; Upadhyaya, Pramod; Lindgren, Bruce R; Roper-Batker, Astia; Hatsukami, Dorothy K; Fritz, Vincent A; Rohwer, Charles; Hecht, Stephen S

2016-10-01

Glucobrassicin in Brassica vegetables gives rise to indole-3-carbinol (I3C), a compound with potent anticancer effects in preclinical models. We previously showed that the urinary metabolite 3,3'-diindolylmethane (DIM) could discriminate between volunteers fed high and low doses of Brassica vegetables. However, the quantitative relationship between glucobrassicin exposure and urinary DIM level is unclear. We conducted a clinical trial to examine the hypotheses that a range of glucobrassicin exposure from Brassica vegetables is reflected in urinary DIM and that this effect plateaus. Forty-five subjects consumed vegetables, a mixture of brussels sprouts and/or cabbage, at one of seven discrete dose levels of glucobrassicin ranging from 25 to 500 μmol, once daily for 2 consecutive days. All urine was collected for 24 hours after each vegetable-eating session. Urinary DIM was measured using our published liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring (LC/ESI-MS/MS-SRM) method. Urinary DIM excretion increased predictably with increasing glucobrassicin dose and plateaued between 200 and 300 μmol of glucobrassicin. The association between glucobrassicin dose and urinary DIM was strong and positive (R 2 = 0.68). The majority of DIM was excreted in the first 12 hours after vegetable consumption. We conclude that urinary DIM is a reliable biomarker of glucobrassicin exposure and I3C uptake and that feeding glucobrassicin beyond 200 μmol did not consistently lead to more urinary DIM, suggesting a plateau in potential chemopreventive benefit. Cancer Prev Res; 9(10); 788-93. ©2016 AACR. ©2016 American Association for Cancer Research.

Dietary administration of sodium arsenite to rats: Relations between dose and urinary concentrations of methylated and thio-metabolites and effects on the rat urinary bladder epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Shugo; Arnold, Lora L.; Pennington, Karen L.

2010-04-15

Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in drinking water is carcinogenic to humans, inducing skin, urinary bladder and lung tumors. In vivo, inorganic arsenic is metabolized to organic methylated arsenicals including the highly toxic dimethylarsinous acid (DMA{sup III}) and monomethylarsonous acid (MMA{sup III}). Short-term treatment of rats with 100 mug/g trivalent arsenic (As{sup III}) as sodium arsenite in the diet or in drinking water induced cytotoxicity and necrosis of the urothelial superficial layer, with increased cell proliferation and hyperplasia. The objectives of this study were to determine if these arsenic-induced urothelial effects are dosemore » responsive, the dose of arsenic at which urothelial effects are not detected, and the urinary concentrations of the arsenical metabolites. We treated female F344 rats for 5 weeks with sodium arsenite at dietary doses of 0, 1, 10, 25, 50, and 100 ppm. Cytotoxicity, cell proliferation and hyperplasia of urothelial superficial cells were increased in a dose-responsive manner, with maximum effects found at 50 ppm As{sup III}. There were no effects at 1 ppm As{sup III}. The main urinary arsenical in As{sup III}-treated rats was the organic arsenical dimethylarsinic acid (DMA{sup V}). The thio-metabolites dimethylmonothioarsinic acid (DMMTA{sup V}) and monomethylmonothioarsinic acid (MMMTA{sup V}) were also found in the urine of As{sup III}-treated rats. The LC{sub 50} concentrations of DMMTA{sup V} for rat and human urothelial cells in vitro were similar to trivalent oxygen-containing arsenicals. These data suggest that dietary As{sup III}-induced urothelial cytotoxicity and proliferation are dose responsive, and the urothelial effects have a threshold corresponding to the urinary excretion of measurable reactive metabolites.« less

The effects of infusions of ring-A-reduced derivatives of aldosterone on the antinatriuretic and kaliuretic actions of aldosterone.

PubMed

Morris, D J; Souness, G W; Saccoccio, N A; Harnik, M

1989-01-01

Infusion of Ring-A-reduced metabolites of aldosterone in adrenalectomized male rats for 4 days revealed that 5 alpha-Ring-A-reduced derivatives, 5 alpha-dihydroaldosterone (5 alpha-DHAldo; 2.5-5.0 micrograms/day), 3 alpha,5 alpha-tetrahydroaldosterone (3 alpha,5 alpha-THAldo; 5-25 micrograms/day), and 3 beta,5 alpha-THAldo (50-175 micrograms/day) possessed intrinsic Na+-retaining activity. The same infusions of 5 alpha-DHAldo, 3 alpha,5 alpha-THAldo, and 3 beta,5 alpha-THAldo, also lowered the urinary excretion of potassium. The 5 beta-Ring-A-reduced derivative 3 alpha,5 beta-THAldo did not demonstrate either of these biological properties. In another set of experiments, on the fourth day of infusion, aldosterone (0.1 microgram/rat) was administered acutely subcutaneously; none of the Ring-A-reduced derivatives altered the Na+-retaining activity of aldosterone. However, in a dose-dependent manner, both 3 alpha,5 alpha-THAldo and 3 beta,5 alpha-THAldo blunted the urinary K+-secretory effect of aldosterone; low dosages of 5 alpha-DHAldo and larger dosages of 3 alpha,5 beta-THAldo did not. Thus, the 5 alpha-reduced derivatives of aldosterone not only lowered urinary Na+ and K+ excretion in their own right, but two of them blunted the kaliuretic response of the parent mineralocorticoid, aldosterone. Further experiments will be required to determine whether these aldosterone metabolites are further metabolized or interconverted during the expression of the regulatory properties described here and whether these properties are physiologically relevant.

Increased urinary excretion rates of serotonin and metabolites during bedrest

NASA Astrophysics Data System (ADS)

Platen, Petra; Lebenstedt, Marion; Schneider, Myriam; Boese, Andrea; Heer, Martina

2005-05-01

Astronauts are often on a voluntarily reduced energy intake during space missions, possibly caused by a metabolic or emotional stress response with involvement of the central serotonergic system (SES). We investigated 24 h urinary excretion (24 h-E) of serotonin (5-HT) and 5-hydroxyindol acidic acid as indicators of the SES in healthy males under two different normocaloric conditions: normal physical activity (NPA) and -6∘ head-down-tilt (HDT). HDT or NPA were randomly arranged with a recovery period of 6 months in between. 24 h-E of hormones varied widely among individuals. Values were higher in HDT compared to NPA. Assuming that the 24 h-E values are, beside being indicators for alterations in the number and metabolism of platelets, Also indicators of central SES, HDT condition seems to activate central SES in a higher degree compared to NPA. Therefore, changes in central SES might be involved in the mechanisms associated with space flight or microgravity, including possible maladaptations such as voluntary undernutrition.

Diagnostic value of potassium level in a spot urine sample as an index of 24-hour urinary potassium excretion in unselected patients hospitalized in a hypertension unit

PubMed Central

Symonides, Bartosz; Wojciechowska, Ewa; Gryglas, Adam; Gaciong, Zbigniew

2017-01-01

Background Primary hyperaldosteronism may be associated with elevated 24-hour urinary potassium excretion. We evaluated the diagnostic value of spot urine (SU) potassium as an index of 24-hour urinary potassium excretion. Methods We measured SU and 24-hour urinary collection potassium and creatinine in 382 patients. Correlations between SU and 24-hour collections were assessed for potassium levels and potassium/creatinine ratios. We used the PAHO formula to estimate 24-hour urinary potassium excretion based on SU potassium level. The agreement between estimated and measured 24-hour urinary potassium excretion was evaluated using the Bland-Altman method. To evaluate diagnostic performance of SU potassium, we calculated areas under the curve (AUC) for SU potassium/creatinine ratio and 24-hour urinary potassium excretion estimated using the PAHO formula. Results Strongest correlation between SU and 24-hour collection was found for potassium/creatinine ratio (r = 0.69, P<0.001). The PAHO formula underestimated 24-hour urinary potassium excretion by mean 8.3±18 mmol/d (95% limits of agreement -28 to +44 mmol/d). Diagnostic performance of SU potassium/creatinine ratio was borderline good only if 24-hour urinary potassium excretion was largely elevated (AUC 0.802 for 120 mmol K+/24 h) but poor with lower values (AUC 0.696 for 100 mmol K+/24 h, 0.636 for 80 mmol K+/24 h, 0.675 for 40 mmol K+/24 h). Diagnostic performance of 24-hour urinary potassium excretion estimated by the PAHO formula was excellent with values above 120 mmol/d and good with lower values (AUC 0.941 for 120 mmol K+/24 h, 0.819 for 100 mmol K+/24 h, 0.823 for 80 mmol K+/24 h, 0.836 for 40 mmol K+/24 h). Conclusions Spot urine potassium/creatinine ratio might be a marker of increased 24-hour urinary potassium excretion and a potentially useful screening test when reliable 24-hour urine collection is not available. The PAHO formula allowed estimation of the 24-hour urinary potassium excretion based on SU measurements with reasonable clinical accuracy. PMID:28662194

Absorption, distribution, metabolism, and excretion of decursin and decursinol angelate from Angelica gigas Nakai.

PubMed

Kim, Kang Min; Kim, Myo Jeong; Kang, Jae Seon

2009-12-01

The pharmacokinetics of decursin and decursinol angelate (D/DA) was investigated in male SD rats following oral and intravenous administration. D/DA and metabolites obtained from in vitro samples were evaluated by LC/MS. The level of D/DA and metabolized decursinol in the blood following oral and intravenous administration declined according to first-order kinetics, with T1/2 values of 56.67, 58.01 and 57.22 h, respectively, being observed after administration of a dose of 2 mg/kg body weight. The large intestine was the major site of disposition following oral administration. These data indicate that D/DA is rapidly absorbed from the gastrointestinal tract. In in vitro experiment utilizing liver microsomal protein, the major metabolic reaction of D/DA occurred to change decursinol. The cumulative biliary, urinary, and fecal excretion of D/DA in bile duct-cannulated rats was 36.10+/-2.9, 25.35+/-3.8, and 34.20+/-3.2%, respectively, at 72 h after administration. These results indicate that the absorption of D/DA is almost complete, and that its metabolites are primarily excreted into feces through the bile. These results indicate that D/DA is subject to enterohepatic circulation.

Stereoselective pharmacokinetics of moguisteine metabolites in healthy subjects.

PubMed

Bernareggi, A; Crema, A; Carlesi, R M; Castoldi, D; Ratti, E; Renoldi, M I; Ratti, D; Ceserani, R; Tognella, S

1995-01-01

We studied the pharmacokinetics of moguisteine, a racemic non-narcotic peripheral antitussive drug, in 12 healthy male subjects after a single oral administration of 200 mg. The unchanged drug was absent in plasma and urine of all subjects. Moguisteine was immediately and completely hydrolyzed to its main active metabolite, the free carboxylic acid M1. Therefore, we evaluated the kinetic profiles of M1, of its enantiomers R(+)-M1 and S(-)-M1, and of M1 sulfoxide optical isomers M2/I and M2/II by conventional and stereospecific HPLC. Maximum plasma concentrations for M1 (2.83 mg/l), M2/I (0.26 mg/l) and M2/II (0.40 mg/l), were respectively reached at 1.3, 1.6 and 1.5 h after moguisteine administration. Plasma concentrations declined after the peak with mean apparent terminal half-lives of 0.65 h (M1), 0.88 h (M2/I) and 0.84 h (M2/II). Most of the administered dose was recovered in urine within 6 h from moguisteine treatment. The systemic and renal clearance values indicated high renal extraction ratio for all moguisteine metabolites, and particularly for M1 sulfoxide optical isomers. Plasma concentration-time profiles and urinary excretion patterns for M1 enantiomers R(+)-M1 and S(-)-M1 were quite similar. Thus, for later moguisteine pharmacokinetic evaluations the investigation of the plasma concentration-time curve and the urinary excretion of the sole racemic M1 through non-stereospecific analytical methods may suffice in most cases.

Association between 24-h urinary sodium excretion and obesity in Korean adults: A multicenter study.

PubMed

Nam, Ga Eun; Kim, Seon Mee; Choi, Mi-Kyeong; Heo, Young-Ran; Hyun, Tai-Sun; Lyu, Eun-Soon; Oh, Se-Young; Park, Hae-Ryun; Ro, Hee-Kyong; Han, Kyungdo; Lee, Yeon Kyung

2017-09-01

The aim of this study was to explore the association between sodium intake, as assessed by 24-h urinary sodium excretion, and various obesity parameters among South Korean adults. The associations of 24-h urinary sodium excretion and sodium intake calculated from the dietary questionnaire with obesity parameters also were compared. This multicenter, cross-sectional study analyzed data of 640 healthy adults from eight provinces in South Korea. Obesity was assessed by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Mean 24-h urinary sodium excretion was calculated from repeatedly collected 24-h urine samples. Participants' dietary intake was assessed by 24-h dietary recall interview on the days before 24-h urine collection. In both sexes, the means of all anthropometric measurements tended to increase proportionally with 24-h urinary sodium excretion quartiles, regardless of adjustment. Men in the highest quartile (Q4) of 24-h urinary sodium excretion had increased odds of obesity (as assessed by BMI, WC, WHR, and WHtR) compared with men in the three lower quartiles (Q1-Q3) of 24-h urinary sodium excretion. Women in Q4 of 24-h urinary sodium excretion exhibited a higher chance of general obesity and abdominal obesity. Sodium intake calculated from the dietary questionnaire was not significantly associated with obesity in either sex. In Korean adults, there was a positive association between higher sodium intake as assessed by 24-h urinary sodium excretion and obesity independent of energy intake. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.

Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare themore » pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.« less

Identification of two main urinary metabolites of (/sup 14/C)omeprazole in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renberg, L.; Simonsson, R.; Hoffmann, K.J.

1989-01-01

The excretion and metabolism of (/sup 14/C)omeprazole given orally as a suspension was studied in 10 healthy male subjects. An average of 79% of the dose was recovered in the urine in 96 hr, with most of the radioactivity (76% of dose) being eliminated in the first 24 hr. Pooled urine (0-2 hr) from five subjects, containing about 47% of the dose, was analyzed by reverse phase gradient elution LC with radioisotope detection. Omeprazole was completely metabolized to at least six metabolites. The two major metabolites were extensively purified by LC and their structures were determined by MS with derivatizationmore » and use of stable isotopes, 1H NMR, and comparison with synthetic references. They were formed by hydroxylation of a methyl group in the pyridine ring, followed by further oxidation of the alcohol to the corresponding carboxylic acid. Both metabolites retained the sulfoxide group of omeprazole, rendering them as unstable as the parent compound at pH less than 7. They accounted for approximately 28% (hydroxyomeprazole) and 23% (omeprazole acid) of the amount excreted in the 0-2-hr collection interval. Based on in vitro studies with the synthetic metabolites in isolated gastric glands, it is unlikely that M1 and M2 will contribute to the pharmacological effect of omeprazole in humans.« less

Simultaneous stereoselective analysis by capillary electrophoresis of tramadol enantiomers and their main phase I metabolites in urine.

PubMed

Rudaz, S; Veuthey, J L; Desiderio, C; Fanali, S

1999-06-18

Capillary zone electrophoresis was successfully applied to the enantiomeric resolution of racemic tramadol and its six phase I metabolites using carboxymethylated beta-cyclodextrin (CMB) added to the background electrolyte (BGE). Baseline resolution of tramadol and its metabolites was obtained in less than 30 min using a 50 mM phosphate buffer (pH 2.5) containing 5 mM of CMB. Chiral determinations of tramadol and its main three metabolites, O-demethyltramadol (M1), N-demethyltramadol (M2) and O-demethyl-N-demethyltramadol (M5), were performed in urine after a simple double liquid-liquid extraction of 200 microliters of biological material. In the tested concentration range (0.5-20 micrograms/ml, except for M2: 0.5-10 micrograms/ml) coefficients of correlation superior than 0.994 were obtained. Within-day variation determined on three different concentrations for each enantiomers showed accuracies ranging from 95.4% to 103.2%. The relative standard deviation (RSD) of these assays was determined to be less than 10.0%. Day-to-day variation presented accuracies ranging from 96.3% to 106.5% with a RSD less than 9.0%. After oral administration of 100 mg of tramadol hydrochloride to an healthy volunteer, the urinary excretion was monitored during 30 h. About 15% of the dose was excreted as unchanged tramadol. The enantiomeric ratios of all the excreted analytes, T, M1, M2 and M5, were found to be very different to 1.0, showing that a stereoselective metabolism of tramadol clearly occurred.

Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

NASA Technical Reports Server (NTRS)

Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Rahlmann, D. F.; Newsom, B. D.

1974-01-01

After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

Dietary intake and urinary excretion of lignans in Finnish men.

PubMed

Nurmi, Tarja; Mursu, Jaakko; Peñalvo, José L; Poulsen, Henrik E; Voutilainen, Sari

2010-03-01

Intake of lignans has been assessed in different study populations, but so far none of the studies has compared the daily intake of lignans and the urinary excretion of plant and enterolignans. We assessed the intake of lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in 100 Finnish men consuming their habitual omnivorous diet, and measured the 24 h urinary excretion of plant and enterolignans to compare the intake and metabolism. Dietary determinants of lignan intake and their urinary excretion were also determined. The mean intake of lignans was 1224 (sd 539) mug/d, of which lariciresinol and pinoresinol covered 78 %. Almost half (47 %) of the intake of lignans was explained by the intake of rye products, berries, coffee, tea and roots. The urinary excretion of plant lignans corresponded to 17 % and enterolignans to 92 % of the intake of lignans. The urinary excretion of plant lignans was explained 14 % by the intake of rye products and intake of coffee, and consequently 3-7 % by the intake of water-insoluble fibre. The urinary excretion of enterolactone was explained 11 % by the intake of vegetables and rye products, 14 % by the intake of water-soluble fibre and only 4 % by the intake of lariciresinol. Although the assessed intake of lignans corresponded well with the urinary excretion of lignans, the enterolactone production in the human body depended more on the dietary sources of lignans than the absolute intake of lignans.

Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

PubMed Central

Rathod, Anita; Bonny, Olivier; Guessous, Idris; Suter, Paolo M.; Conen, David; Erne, Paul; Binet, Isabelle; Gabutti, Luca; Gallino, Augusto; Muggli, Franco; Hayoz, Daniel; Péchère-Bertschi, Antoinette; Paccaud, Fred

2015-01-01

Background and objectives Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. Design, settings, participants, & measurements Multivariable linear regression was used to explore factors associated with square root–transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. Results In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15–95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein–corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, −0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, −0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. Conclusions There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion. PMID:25518946

Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico.

PubMed

Meza, Maria Mercedes; Kopplin, Michael J; Burgess, Jefferey L; Gandolfi, A Jay

2004-10-01

The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations.

Effects of chronic lithium administration on renal acid excretion in humans and rats

PubMed Central

Weiner, I. David; Leader, John P.; Bedford, Jennifer J.; Verlander, Jill W.; Ellis, Gaye; Kalita, Priyakshi; Vos, Frederiek; de Jong, Sylvia; Walker, Robert J.

2014-01-01

Abstract Lithium therapy's most common side effects affecting the kidney are nephrogenic diabetes insipidus (NDI) and chronic kidney disease. Lithium may also induce a distal renal tubular acidosis. This study investigated the effect of chronic lithium exposure on renal acid–base homeostasis, with emphasis on ammonia and citrate excretion. We compared 11 individuals on long‐term lithium therapy with six healthy individuals. Under basal conditions, lithium‐treated individuals excreted significantly more urinary ammonia than did control subjects. Following an acute acid load, urinary ammonia excretion increased approximately twofold above basal rates in both lithium‐treated and control humans. There were no significant differences between lithium‐treated and control subjects in urinary pH or urinary citrate excretion. To elucidate possible mechanisms, rats were randomized to diets containing lithium or regular diet for 6 months. Similar to humans, basal ammonia excretion was significantly higher in lithium‐treated rats; in addition, urinary citrate excretion was also significantly greater. There were no differences in urinary pH. Expression of the critical ammonia transporter, Rhesus C Glycoprotein (Rhcg), was substantially greater in lithium‐treated rats than in control rats. We conclude that chronic lithium exposure increases renal ammonia excretion through mechanisms independent of urinary pH and likely to involve increased collecting duct ammonia secretion via the ammonia transporter, Rhcg. PMID:25501430

6β-HYDROXYTESTOSTERONE, A CYTOCHROME P450 1B1-TESTOSTERONE-METABOLITE, MEDIATES ANGIOTENSIN II-INDUCED RENAL DYSFUNCTION IN MALE MICE

PubMed Central

Pingili, Ajeeth K.; Thirunavukkarasu, Shyamala; Kara, Mehmet; Brand, David; Katsurada, Akemi; Majid, Dewan S. A.; Navar, L. Gabriel; Gonzalez, Frank J.; Malik, Kafait U.

2016-01-01

6β-hydroxytestosterone, a cytochrome P450 1B1-derived metabolite of testosterone, contributes to the development of angiotensin II-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of angiotensin II in the maintenance of renal homeostasis, development of hypertension and end organ damage, this study was conducted to determine the contribution of 6β-hydroxytestosterone to angiotensin II actions on water consumption and renal function in male Cyp1b1+/+ and Cyp1b1−/− mice. Castration of Cyp1b1+/+ mice or Cyp1b1−/− gene disruption minimized the angiotensin II-induced increase in water consumption, urine output, proteinuria, and sodium excretion and decreases in urine osmolality. 6β-hydroxytestosterone did not alter angiotensin II-induced increases in water intake, urine output, proteinuria, and sodium excretion or decreases in osmolality in Cyp1b1+/+ mice, but restored these effects of angiotensin II in Cyp1b1−/− or castrated mice Cyp1b1+/+ mice. Cyp1b1 gene disruption or castration prevented angiotensin II-induced renal fibrosis, oxidative stress, inflammation, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, and angiotensin converting enzyme. 6β-hydroxytestosterone did not alter angiotensin II-induced renal fibrosis, inflammation, oxidative stress, urinary excretion angiotensinogen, expression of angiotensin II type 1 receptor, or angiotensin converting enzyme in Cyp1b1+/+ mice; however, in Cyp1b1−/− or castrated mice Cyp1b1+/+ mice, it restored these effects of angiotensin II. These data indicate that 6β-hydroxytestosterone contributes to increased thirst, impairment of renal function, and end organ injury associated with angiotensin II-induced hypertension in male mice and that cytochrome P450 1B1 could serve as a novel target for treating renal disease and hypertension in males. PMID:26928804

A cutaneous full-thickness liquid sulfur mustard burn model in weanling swine: clinical pathology and urinary excretion of thiodiglycol.

PubMed

Graham, J S; Reid, F M; Smith, J R; Stotts, R R; Tucker, E S; Shumaker, S M; Niemuth, N A; Janny, S J

2000-12-01

Sulfur mustard (bis(2-chloroethyl)sulfide, HD) is a well-known blistering chemical warfare agent. We have developed a cutaneous full-thickness HD burn model in weanling pigs for efficacy testing of candidate treatment regimens. This report addresses clinical pathology findings and the urinary excretion profile of a major HD metabolite (thiodiglycol, TDG) in this model. Six female Yorkshire pigs were exposed to HD liquid on the ventral surface for 2 h, generating six 3-cm diameter full-thickness dermal lesions per pig. Blood samples were collected throughout a 7-day observation period for hematology and serum chemistry examinations. Urine was collected in metabolism cages. Routine urinalysis was performed and the urine analyzed for TDG using gas chromatography/mass spectrometry. Examination of clinical pathology parameters revealed subtle HD-related changes that are suggestive of a mild hemolytic episode. No other signs of clinically significant systemic toxicities were noted, including bone marrow suppression. Thiodiglycol was detected at the earliest time point tested (6-8 h post-exposure) at levels ranging from 0.66 to 4.98 microg ml(-1) with a mean of 2.14 microg ml(-1). Thiodiglycol concentrations were the highest for half of the animals at this earliest time point and at 24-48 h for the others. By the evening of day 3, the mean level had reached 50 ng ml(-1). Mean levels remained 10-40 ng ml(-1) for the remainder of the 7-day observation period, with the highest individual concentration noted during this period of 132 ng ml(-1). Our results are in general agreement with the TDG excretion profiles previously described for rodent models and humans. Urinary excretion of absorbed HD in our weanling pig wound healing model appears to follow the same pattern as is seen in other laboratory animals models. In general, urinary excretion of TDG appears to peak within the first 1-4 days following exposure, with detectable levels after 1 week. Relatively high urinary TDG levels may thus indicate agent exposure within the previous 96 h. Low levels significantly above natural background levels may indicate either exposure to low levels of agent or exposure that occurred more than 4 days prior to collection of the sample.

Decreased urinary glycosaminoglycan excretion following alfuzosin treatment on ureteral stent-related symptoms: a prospective, randomized, placebo-controlled study.

PubMed

Liu, Shucheng; Yu, Ying; Gao, Yang; Yang, Xiong; Pang, Zili

2016-04-01

The objectives of the study were to evaluate changes in ureteral stent-related symptoms and urinary glycosaminoglycan (GAG) excretion after alfuzosin treatment, and to further investigate the relationship between stent-related symptoms and loss of urinary GAGs. Seventy consecutive patients scheduled for unilateral retrograde ureteroscopy with stent placement were recruited. Patients were randomly assigned to treatment with alfuzosin 10 mg/day or placebo for 3 weeks starting on the third postoperative day. The ureteral stent was removed when treatment stopped. International Prostate Symptom Score (IPSS), visual analog scale (VAS) score, and urinary GAG excretion were determined before treatment at 1, 2, and 3 weeks after treatment, and at 3 weeks after stent removal. Fifty-nine patients completed the study. IPSS, VAS score, and urinary GAG excretion were significantly lower in the alfuzosin group, compared with the placebo group, at 1, 2, and 3 weeks after treatment (P < 0.01). In both groups, IPSS, VAS score, and urinary GAG excretion were significantly lower at 3 weeks after stent removal compared with those before stent removal. No significant differences in IPSS, VAS score, or urinary GAG excretion were observed between the two groups at baseline and 3 weeks after stent removal (P > 0.05). Positive correlations were found between urinary GAG excretion (R(2) = 0.65, P < 0.001) and IPSS and between urinary GAG excretion and VAS score (R(2) = 0.33, P < 0.001). Stent placement contributes to loss of urinary GAGs. However, alfuzosin effectively reduces such loss and improves ureteral stent-related symptoms. Loss of urinary GAGs plays a role in these symptoms.

The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

PubMed

Ma, Feng-Wei; Deng, Qing-Fang; Zhou, Xin; Gong, Xiao-Jian; Zhao, Yang; Chen, Hua-Guo; Zhao, Chao

2016-03-24

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.

Nontargeted LC-MS Metabolomics Approach for Metabolic Profiling of Plasma and Urine from Pigs Fed Branched Chain Amino Acids for Maximum Growth Performance.

PubMed

Soumeh, Elham A; Hedemann, Mette S; Poulsen, Hanne D; Corrent, Etienne; van Milgen, Jacob; Nørgaard, Jan V

2016-12-02

The metabolic response in plasma and urine of pigs when feeding an optimum level of branched chain amino acids (BCAAs) for best growth performance is unknown. The objective of the current study was to identify the metabolic phenotype associated with the BCAAs intake level that could be linked to the animal growth performance. Three dose-response studies were carried out to collect blood and urine samples from pigs fed increasing levels of Ile, Val, or Leu followed by a nontargeted LC-MS approach to characterize the metabolic profile of biofluids when dietary BCAAs are optimum for animal growth. Results showed that concentrations of plasma hypoxanthine and tyrosine (Tyr) were higher while concentrations of glycocholic acid, tauroursodeoxycholic acid, and taurocholic acid were lower when the dietary Ile was optimum. Plasma 3-methyl-2-oxovaleric acid and creatine were lower when dietary Leu was optimum. The optimum dietary Leu resulted in increased urinary excretion of ascorbic acid and choline and relatively decreased excretion of 2-aminoadipic acid, acetyl-dl-valine, Ile, 2-methylbutyrylglycine, and Tyr. In conclusion, plasma glycocholic acid and taurocholic acid were discriminating metabolites to the optimum dietary Ile. The optimum dietary Leu was associated with reduced plasma creatine and urinary 2-aminoadipic acid and elevated urinary excretion of ascorbic acid and choline. The optimum dietary Val had a less pronounced metabolic response reflected in plasma or urine than other BCAA.

[Dubin-Johnson syndrome: molecular basis and pathogenesis].

PubMed

Mzabi-Regaya, Sabah; Chadli-Debbiche, Aschraf; Ben Brahim, Ehsen; Gritli, Sami; Goutallier-Ben Fadhel, Carole; Khalfallah, Mohamed Tahar

2002-04-01

The Dubin-Johnson syndrome (DJS) is an autosomal recessive liver disorder characterized by a chronic conjugated hyperbilirubinemia a dark greenish appearance of liver tissue, a double peaked sulfobromophthalein clearance curve, and a characteristic lysosomal accumulation of black pigment "melanine-like" in the hepatocytes. Laboratory datas indicated an increased urinary excretion of coproporphrin isomer I and leukotriene metabolites. In an effort to understand the morphological pattern and the pathogenesis of this disease we reviewed four cases of DJS.

Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.

PubMed

Burke, C W; Shakespear, R A

1976-03-01

Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.

Evidence that histamine is the causative toxin of scombroid-fish poisoning.

PubMed

Morrow, J D; Margolies, G R; Rowland, J; Roberts, L J

1991-03-14

The highest morbidity worldwide from fish poisoning results from the ingestion of spoiled scombroid fish, such as tuna and mackerel, and its cause is not clear. Histamine could be responsible, because spoiled scombroid fish contain large quantities of histamine. Whether histamine is the causative toxin, however, has remained in question. To address this issue, we investigated whether histamine homeostasis is altered in poisoned people. The urinary excretion of histamine and its metabolite, N-methylhistamine, was measured in three persons who had scombroid-fish poisoning (scombrotoxism) after the ingestion of marlin. We measured 9 alpha, 11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid (PGD-M), the principal metabolite of prostaglandin D2, a mast-cell secretory product, to assess whether mast cells had been activated to release histamine. The fish contained high levels of histamine (842 to 2503 mumol per 100 g of tissue). Symptoms of scombrotoxism--flushing and headache--began 10 to 30 minutes after the ingestion of fish. In urine samples collected one to four hours after fish ingestion, the levels of histamine and N-methylhistamine were 9 to 20 times and 15 to 20 times the normal mean, respectively. During the subsequent 24 hours, the levels fell to 4 to 15 times and 4 to 11 times the normal values. Levels of both were normal 14 days later. PGD-M excretion was not increased at any time. Two persons treated with diphenhydramine had prompt amelioration of symptoms. Scombroid-fish poisoning is associated with urinary excretion of histamine in quantities far exceeding those required to produce toxicity. The histamine is most likely derived from the spoiled fish. These results identify histamine as the toxin responsible for scombroid-fish poisoning.

Population-based association between urinary excretion of sodium, potassium and its ratio with albuminuria in Chinese.

PubMed

Yan, Liuxia; Guo, Xiaolei; Wang, Huicheng; Zhang, Jiyu; Tang, Junli; Lu, Zilong; Cai, Xiaoning; Liu, Longjian; Gracely, Edward J; Ma, Jixiang

2016-12-01

Albuminuria is a risk factor for cardiovascular and renal disease. However, little is known about the association of 24 h urinary sodium and potassium excretion with albuminuria in China. The aim of this study was to examine this association by analyzing the data from 1,975 Chinese adults living in north China. Excretion of urinary sodium, potassium and albumin was assessed in a single 24-h urine sample for each participant. Height, weight, waist circumference and blood pressure were measured and body mass index was determined as weight divided by square height. Fasting blood sample was collected and fasting glucose was measured. The average 24-h urinary sodium and potassium excretion were 232 mmol and 40.8 mmol, resulting a mean sodium to potassium ratio of 6.7. The median (Q1-Q3) 24-h urinary albuminuria excretion was 6.1 mg (4.5-8.7 mg). Overall, urinary sodium excretion was positively associated with albumin excretion (β=0.029, p<0.001). This association was independent of major cardiovascular risk factors including age, gender, systolic blood pressure, body mass index, fasting glucose, waist circumference, hypertensive drug treatment, and smoking. Moreover, the relation of sodium and albumin was similar in the subgroups stratified by gender, adiposity and diabetic status. No significant associations of potassium excretion or sodium to potassium ratio with urinary albumin excretion were observed. In cross-sectional analyses, high sodium intake was shown to be associated with increased urinary albuminuria in the general Chinese adult population, supporting salt restriction for renal and cardiovascular health benefit.

Effect of Ramadan fasting on urinary risk factors for calculus formation.

PubMed

Miladipour, Amir Hossein; Shakhssalim, Nasser; Parvin, Mahmoud; Azadvari, Mohaddeseh

2012-01-01

Even though dehydration could aggravate formation of urinary calculi, the effects of fluid and food restriction on calculus formation is not thoroughly defined. The purpose of this study is to evaluate the effects of fluid and food restriction in Ramadan fasting on urinary factors in kidney and urinary calculus formation. Fifty-seven men aged 30 to 55 years old, including 37 recurrent calcium calculus formers and 20 with no history of kidney calculi were evaluated for blood tests, ultrasonography investigations, urinalysis, urine culture, and also 24-hour urine collection test. Metabolites including calcium, oxalate, citrate, uric acid, magnesium, phosphate, potassium, sodium, and creatinine were measured before and during Ramadan fasting. The values of calculus-precipitating solutes as well as inhibitory factors were documented thoroughly. Total excretion of calcium, phosphate, and magnesium in 24-hour urine and also urine volume during fasting were significantly lower than those in the nonfasting period. Urine concentration of calcium during fasting was significantly lower than nonfasting (P < .001). Urine concentrations of uric acid, citrate, phosphate, sodium, and potassium during fasting were significantly higher than nonfasting. Uric acid supersaturation was accentuated, and calcium phosphate supersaturation was decreased significantly during fasting. There was no significant increase in calcium oxalate supersaturation during the fasting period. Fasting during Ramadan has different effects on total excretion and concentrations of urinary precipitate and inhibitory factors contributing to calculus formation. We did not find enough evidence in favor of increased risks of calculus formation during Ramadan fasting.

Disposition and metabolism of the bisphenol analogue, bisphenol S, in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans.

PubMed

Waidyanatha, Suramya; Black, Sherry R; Snyder, Rodney W; Yueh, Yun Lan; Sutherland, Vicki; Patel, Purvi R; Watson, Scott L; Fennell, Timothy R

2018-07-15

With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [ 14 C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72 h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [ 14 C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (DTMBA) as a new potential biomarker of exposure to vinclozolin in urine.

PubMed

Cruz-Hurtado, Marycarmen; López-González, Ma de Lourdes; Escobar-Wilches, Derly Constanza; Sierra-Santoyo, Adolfo

2018-05-01

Vinclozolin (V) is a fungicide with anti-androgenic properties whose metabolism is not fully understood, and data on urinary elimination of either V or its metabolites are limited. Therefore the kinetics of urinary elimination of V and its metabolites, after an oral dose in adult male rats were investigated. A single oral dose of V (100 mg/kg) suspended in corn oil was administered to male adult Wistar rats, and urine was collected at different times after dosing. V and its metabolites were extracted from urine, then enzymatically hydrolyzed using β-glucuronidase/sulfatase of H. pomatia, and analyzed by HPLC/DAD. Urinary pharmacokinetic parameters were calculated using the analyte concentrations adjusted by creatinine levels. V and its metabolites 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (DTMBA, formerly denoted as M5), 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), 3,5-dichloroaniline (M3), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2) were efficiently detected. The mean urine concentrations of V and M1 metabolite were fitted to a two-compartmental model for pharmacokinetic analysis. DTMBA approximately represented 88% of the total excreted metabolites, it was easily detected up to 168 h after dosing and its half-lives were 21.5 and 74.1 h, respectively. M1 was the second most abundant metabolite and was detected up to 144 h after being void. V and M3 were detected before 48 h, and M2 exhibited the lowest levels during the first 8 h after dosing. DTMBA, the most abundant V metabolite is quickly eliminated by urine, it is chemically stable, specific and could represent a useful alternative to be used as a biomarker of exposure to V. Copyright © 2018 Elsevier Inc. All rights reserved.

Urinary spot albumin:creatinine ratio for documenting proteinuria in women with preeclampsia.

PubMed

Huang, Qitao; Gao, Yunfei; Yu, Yanhong; Wang, Wei; Wang, Shuoshi; Zhong, Mei

2012-01-01

To assess whether a single urinary spot urinary albumin:creatinine ratio (ACR) can be used to estimate 24-hour urinary protein excretion in women with preeclampsia. ACR and 24-hour urinary protein excretion were measured in 50 consecutive patients with preeclampsia. ACR was determined in a spot midstream urine sample and the amount of protein excretion was quantified in a 24-hour urine collection performed the following day. The correlation between the spot ACR and 24-hour urine protein excretion was assessed, and the diagnostic value of ACR was expressed in terms of specificity and sensitivity. Receiver operating characteristic curve analysis was used to determine the best cutoff values of the spot ACR for mild preeclampsia (proteinuria ≥ 0.3 g/24 h) and severe preeclampsia (defined in China as proteinuria ≥ 2 g/24 h). A strong correlation was evident between the spot ACR and 24-hour urinary protein excretion (r = .938; P < .001). The optimal spot ACR cutoff point was 22.8 mg/mmol for 0.3 g/24 h of protein excretion (mild preeclampsia) with a sensitivity and specificity of 82.4% and 99.4%, respectively, and 155.6 mg/mmol for 2 g/24 h of protein excretion (severe preeclampsia) with a sensitivity and specificity of 90.6% and 99.6%, respectively. Compared with 24-hour urinary protein excretion, the spot urinary ACR may be a simple, convenient, and accurate indicator of significant proteinuria in women with preeclampsia.

Relationships between urinary electrolytes excretion and central hemodynamics, and arterial stiffness in hypertensive patients.

PubMed

Han, Weizhong; Han, Xiao; Sun, Ningling; Chen, Yunchao; Jiang, Shiliang; Li, Min

2017-08-01

High sodium intake plays an important role in the onset and exacerbation of hypertension. However, the relationships between urinary electrolytes excretion and central hemodynamics and between urinary electrolyte excretion and arterial stiffness are still the subject of debate. This study sought to clarify the associations of salt intake with central aortic pressure and arterial stiffness indicators. A total of 431 untreated hypertensive individuals were recruited into the study. Twenty-four-hour urinary samples were collected to measure the excretion of urinary electrolytes. Central hemodynamics parameters and brachial-ankle pulse wave velocity (baPWV) were measured. We evaluated the independent relationship between urinary sodium or potassium excretion and the abovementioned indices. The mean 24-h urinary sodium of all subjects was 166.6±70.0 mmol/24 h. With increases in urinary sodium excretion, central blood pressure and baPWV values markedly increased. Multiple regression analysis showed that urinary sodium was independently associated with increases in central systolic blood pressure, central diastolic blood pressure, the augmentation index, and baPWV. Significant correlations were identified between high dietary sodium and central hemodynamics and between high dietary sodium and arterial elasticity. Prospective interventional studies in hypertensive patients may be required to determine the effect of salt intake on central hemodynamics.

Nandrolone excretion is not increased by exhaustive exercise in trained athletes.

PubMed

Schmitt, Nelly; Flament, Marie-Madeleine; Goubault, Claude; Legros, Patrick; Grenier-Loustalot, Marie France; Denjean, André

2002-09-01

The anabolic steroid nandrolone is widely used as a performance enhancer. Traces of its naturally occurring metabolite 19-norandrosterone (19-NA) have been found in human urine (below 0.6 ng.mL(-1)), and it has been suggested that strenuous exercise may increase urinary 19-NA. The aim of our study was to assess the effect of exhaustive exercise on the nandrolone excretion under controlled conditions in two groups of trained male athletes, one composed of judoka and the other of long-distance runners. A Wingate test and a treadmill limited-time test (running at 85% (.)VO(2max)) were carried out on 14 judoka and 15 athletes. Hydration was controlled during each session. Urine samples were obtained before each test and 30 min, 60 min, and 24 h after each test. Urinary 19-NA concentrations were determined using gas chromatography coupled with mass spectrometry. Baseline urinary 19-NA concentrations varied widely across individuals, from undetectable levels to 0.250 ng.mL (-1)(mean, 0.048 +/- 0.050 ng.mL(-1)). The both exercise tests did not significantly modified urinary 19-NA levels in the two groups of subjects. Our study provides compelling evidence that endogenous nandrolone production in male athletes, during two very different types of exercise, produces urine levels far below the IOC threshold of 2 ng.mL(-1) urine. Thus, exercise does not induce endogenous nandrolone secretion.

Reference limits for urinary fractional excretion of electrolytes in adult non-racing Greyhound dogs.

PubMed

Bennett, S L; Abraham, L A; Anderson, G A; Holloway, S A; Parry, B W

2006-11-01

To determine reference limits for urinary fractional excretion of electrolytes in Greyhound dogs. Urinary fractional excretion was calculated using a spot clearance method preceded by a 16 to 20 hour fast in 48 Greyhound dogs. Raw data analysed using the bootstrap estimate was used to calculate the reference limits. The observed range for urinary fractional excretion in Greyhound dogs was 0.0 to 0.77% for sodium, 0.9 to 14.7% for potassium, 0 to 0.66% for chloride, 0.03 to 0.22% for calcium and 0.4 to 20.1% for phosphate. Expressed as percentages, the suggested reference limits for fractional excretion in Greyhound dogs are as follows: sodium < or = 0.72, potassium < or = 12.2, chloride < or = 0.55, calcium < or = 0.13 and phosphate < or = 16.5. Veterinary practitioners may use these reference limits for urinary electrolyte fractional excretion when investigating renal tubular disease in Greyhound dogs.

Pharmacokinetics of S-Allyl-l-cysteine in Rats Is Characterized by High Oral Absorption and Extensive Renal Reabsorption.

PubMed

Amano, Hirotaka; Kazamori, Daichi; Itoh, Kenji

2016-02-01

S-Allylcysteine (SAC) is a key component of aged garlic extract, one of many garlic products. However, information on its pharmacokinetics has been scant except for data from a few animal studies. We designed this study to determine the overall pharmacokinetics of SAC in rats. After oral or intravenous administration of SAC to rats at a dose of 5 mg/kg, the plasma concentration-time profile of SAC and its metabolites, as well as the amounts excreted in bile and urine, were analyzed by using liquid chromatography tandem mass spectrometry. After oral administration, SAC was well absorbed with a bioavailability of 98%. Two major metabolites of SAC, N-acetyl-S-allylcysteine (NAc-SAC) and N-acetyl-S-allylcysteine sulfoxide (NAc-SACS), were detected in plasma, but their concentrations were markedly lower than those of SAC. SAC was metabolized to a limited extent, but most of the orally absorbed SAC was excreted into urine in the form of its N-acetylated metabolites. The amounts of SAC, NAc-SAC, and NAc-SACS excreted in urine over 24 h were 2.9%, 80%, and 11% of the orally administered SAC, respectively. The very low renal clearance (0.016 L ⋅ h(-1) ⋅ kg(-1)) of SAC indicated that it undergoes extensive renal reabsorption. These results collectively suggested that SAC was ultimately metabolized to NAc-SAC and NAc-SACS through the cycles of urinary excretion, renal reabsorption, and systemic recirculation. The pharmacokinetics of SAC in rats were characterized by high oral absorption, limited metabolism, and extensive renal reabsorption, all of which potentially contribute to its high and relatively long-lasting plasma concentrations. © 2016 American Society for Nutrition.

Bioavailability of chlorogenic acids following acute ingestion of coffee by humans with an ileostomy.

PubMed

Stalmach, Angélique; Steiling, Heike; Williamson, Gary; Crozier, Alan

2010-09-01

The intestinal absorption and metabolism of 385 micromol chlorogenic acids following a single intake of 200 mL of instant coffee by human volunteers with an ileostomy was investigated. HPLC-MS(3) analysis of 0-24h post-ingestion ileal effluent revealed the presence of 274+/-28 micromol of chlorogenic acids and their metabolites accounting for 71+/-7% of intake. Of the compounds recovered, 78% comprised parent compounds initially present in the coffee, and 22% were metabolites including free and sulfated caffeic and ferulic acids. Over a 24h period after ingestion of the coffee, excretion of chlorogenic acid metabolites in urine accounted for 8+/-1% of intake, the main compounds being ferulic acid-4-O-sulfate, caffeic acid-3-O-sulfate, isoferulic acid-3-O-glucuronide and dihydrocaffeic acid-3-O-sulfate. In contrast, after drinking a similar coffee, urinary excretion by humans with an intact colon corresponded to 29+/-4% of chlorogenic acid intake. This difference was due to the excretion of higher levels of dihydroferulic acid and feruloylglycine together with sulfate and glucuronide conjugates of dihydrocaffeic and dihydroferulic acids. This highlights the importance of colonic metabolism. Comparison of the data obtained in the current study with that of Stalmach et al. facilitated elucidation of the pathways involved in post-ingestion metabolism of chlorogenic acids and also helped distinguish between compounds absorbed in the small and the large intestine. Copyright © 2010 Elsevier Inc. All rights reserved.

Biotransformation and mass balance of tipranavir, a nonpeptidic protease inhibitor, when co-administered with ritonavir in Sprague-Dawley rats.

PubMed

Macha, Sreeraj; Chen, Linzhi; Norris, Stephen H; Philip, Elsy; Mao, Yanping; Silverstein, Helga; Struble, Craig; Beers, Wendy

2007-09-01

In this study, tipranavir (TPV) biotransformation and disposition when co-administered with ritonavir (RTV) were characterized in Sprague-Dawley rats. Rats were administered a single intravenous (5 mg kg(-1)) or oral (10 mg kg(-1)) dose of [(14)C]TPV with co-administration of RTV (10 mg kg(-1)). Blood, urine, faeces and bile samples were collected at specified time-points over a period of 168 h. Absorption of TPV-related radioactivity ranged from 53.2-59.6%. Faecal excretion was on average 86.7% and 82.4% (intravenous) and 75.0% and 82.0% (oral) of dosed radioactivity in males and females, respectively. Urinary excretion was on average 4.06% and 6.73% (intravenous) and 9.71% and 8.28% (oral) of dosed radioactivity in males and females, respectively. In bile-duct-cannulated rats, 39.8% of the dose was recovered in bile. After oral administration, unchanged TPV accounted for the majority of the radioactivity in plasma (85.7-96.3%), faeces (71.8-80.1%) and urine (33.3-62.3%). The most abundant metabolite in faeces was an oxidation metabolite R-2 (5.9-7.4% of faecal radioactivity, 4.4-6.1% of dose). In urine, no single metabolite was found to be significant, and comprised <1% of dose. TPV when co-administered with RTV to rats was mainly excreted in feces via bile and the parent compound was the major component in plasma and faeces.

Urinary 1-hydroxypyrene in coke oven workers relative to exposure, alcohol consumption, and metabolic enzymes

PubMed Central

Zhang, J; Ichiba, M; Hara, K; Zhang, S; Hanaoka, T; Pan, G; Yamano, Y; Takahashi, K; Tomokuni, K

2001-01-01

OBJECTIVES—To investigate the influence of personal lifestyle—such as smoking and alcohol consumption—on urinary 1-hydroxypyrene (1-OHP) concentrations in coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) and to evaluate the association of 1-OHP concentrations with the genetic polymorphism of several metabolic enzymes including cytochrome P-450 (CYP) 1A1 and glutathione S-tranferases (GSTs).
METHODS—The study population contained 162 coke oven workers and 58 controls employed at the largest iron and steel factory in China. Personal data were collected at the interview. 1-OHP in urine was measured with high performance liquid chromatography with fluorescence detection. Genetic polymorphisms were identified by the polymerase chain reaction (PCR) method.
RESULTS—A positive association between excretion of urinary 1-OHP and the levels of exposure to PAHs was confirmed. Those people who consumed ⩾50 g/day ethanol had significantly higher 1-OHP excretion than did other coke oven workers (p<0.01). No significant difference in urinary 1-OHP was found between smokers and non-smokers, in both controls and exposed subjects. The variant homozygotes at exon 7 of the CYP1A1 gene had significantly higher urinary 1-OHP concentrations than other CYP1A1 genotypes among the exposed workers (p=0.03). There was less association between the concentrations of 1-OHP and the GSTM1, GSTP1, or GSTT1 polymorphism.
CONCLUSIONS—The present study confirmed that urinary 1-OHP is a good biomarker for exposure to PAHs. Alcohol consumption affected urinary 1-OHP excretion. The variant genotypes of the CYP1A1 gene may result in the enhancement of PAH metabolites. It is helpful to understand the role of individual susceptibility on metabolism of carcinogens. These findings suggest that the modulating effect of individual lifestyle factors or genetic nature should be considered in future studies on occupational exposure to PAHs and in evaluating the health risk from harmful chemicals.


Keywords: 1-hydroxypyrene; genetic polymorphism; alcohol drinking PMID:11600727

Detection of rare species of volatile organic selenium metabolites in male golden hamster urine.

PubMed

Kwak, Jae; Ohrnberger, Sarah A; Valencak, Teresa G

2016-07-01

Selenium has been considered as an essential trace element in mammals and its intake comes mainly from food. Mammals can metabolize both inorganic and organic species, and urinary excretion is the primary elimination route of selenium. Selenosugars and trimethylselenonium ion have been identified as major urinary metabolites. Other metabolites have been reported, but they were detected in some studies and not in others. Still, a large portion of the ingested selenium eliminated from the body is unknown. Volatile selenium species may account for a certain portion of the unknown species since they can easily be lost during sample analyses. While we analyzed male golden hamster urine in search of potential volatile pheromone(s), four volatile selenium compounds were detected. They were dimethyl selenenylsulfide, dimethyl diselenide, dimethyl bis(thio)selenide, and dimethyl selenodisulfide. When the urine samples were aged and dried for 48 h, dimethyl selenodisulfide tended to increase, while others decreased. The increase might be due to the formation of dimethyl selenodisulfide via reaction of dimethyl diselenide and dimethyl trisulfide whose concentration increased as urine aged. To our knowledge, dimethyl bis(thio)selenide and dimethyl selenodisulfide have never been demonstrated in urine. It remains to be determined whether these species are common metabolites in other animals or hamster-specific.

Urinary phthalate excretion in 555 healthy Danish boys with and without pubertal gynaecomastia.

PubMed

Mieritz, Mikkel G; Frederiksen, Hanne; Sørensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Hagen, Casper P; Skakkebaek, Niels E; Andersson, Anna-Maria; Juul, Anders

2012-06-01

Pubertal gynaecomastia is a clinical sign of an oestrogen-androgen imbalance, which occurs in 40-60% of adolescent Caucasian boys. In most cases no underlying endocrinopathy can be identified. A recent study reports higher plasma phthalate levels in Turkish boys with pubertal gynaecomastia. Therefore, we asked whether there was an association between concurrent measures of urinary phthalate metabolites and pubertal timing as well as the presence of gynaecomastia in otherwise healthy boys. We studied a total of 555 healthy boys (age 6.07-19.83 years) as part of the COPENHAGEN Puberty Study. Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed. Non-fasting blood samples were analysed for serum testosterone and morning urine samples were analysed for the total content of 12 phthalate metabolites (MEP, MnBP, MiBP, MBzP, MEHP, MEHHP, MEOHP, MECPP, MiNP, MHiNP, MiONP and MCiOP) by LC-MS/MS. A statistically significant negative correlation was observed between chronological age and the urinary concentration of the sum of measured metabolites DEHP (∑DEHPm) (r = -0.164) and DiNP (∑DiNPm) (r = -0.224), respectively, and the sum of monobutyl phthalate (MBP) isomers (∑MBP((i+n))) (r = -0.139) (all with p < 0.01). In contrast urinary monoethyl phthalate concentration was positively correlated to age (r = 0.187, p < 0.01). The urinary levels of phthalate metabolites were not associated with age at pubertal onset, serum testosterone levels or presence of gynaecomastia. In conclusion, we did not find evidence of anti-androgenic effects of phthalates in our healthy boys. Thus, current phthalate exposure was not associated with pubertal timing, testosterone levels or with the presence of pubertal gynaecomastia in this cross-sectional study. However, longitudinal studies are needed to evaluate possible perinatal or long-term postnatal effects of phthalates on healthy boys. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

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

PubMed

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.

Normal distribution of urinary polyphenol excretion among Egyptian males 7-14 years old and changes following nutritional intervention with tomato juice (Lycopersicon esculentum).

PubMed

Hussein, Laila; Medina, Alexander; Barrionnevo, Ana; Lammuela-Raventos, Rosa M; Andres-Lacueva, Cristina

2009-06-01

The urinary flavonoids are considered a reliable biomarker for the intake of polyphenol-rich foods. To assess the normal distribution of urinary polyphenol [PP] excretion among healthy male children and adolescents on a typical Egyptian diet. To follow up the impact of nutritional intervention with tomato juice on the urinary excretion of [PP]. Forty-nine male subjects 7-14 years old collected a 24-h urine sample and filled a dietary record during a 7-day period. A daily serving of 230 g fresh tomato juice was followed for 18 days in a subgroup. Total urinary [PP] excretions were measured before and after termination of the intervention program. The total urinary [PP] was analyzed after a clean-up solid-phase extraction step by the Folin-Ciocalteu reagent in the 96 micro plates. The results were expressed as gallic acid equivalents (GAE). The urinary [PP] excretion averaged 48.6+/-5.5 mg GAE/24 h, equivalent to 89.5+/-8.4 mg GAE/g creatinine. The mean urinary [PP] excretion increased significantly (P<0.05) following the intervention with tomato juice (287.4+/-64.3 mg GAE/g creatinine) compared with the respective mean baseline level (94.5+/-8.92 mg GAE/g creatinine). Clinical laboratory reference limits for urinary polyphenols are presented for Egyptian male children and adolescents. Measuring the urinary polyphenol excretion proved a good biomarker for the dietary polyphenol intake and the results demonstrated that tomato [PP] was highly bioavailable in the human body.

Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies.

PubMed

Martin, Paul; Oliver, Stuart; Gillen, Michael; Marbury, Thomas; Millson, David

2015-12-01

Phase III trials of fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis have been completed. Herein, we report the effects of renal and hepatic impairment on the pharmacokinetic (PK) properties of the active metabolite of fostamatinib, R406, in plasma, and on the urinary excretion of R406 and its metabolite N-glucuronide. Two Phase I, single-center, open-label clinical trials determined the PK properties and tolerability of fostamatinib in subjects with normal or impaired renal or hepatic function. Twenty-four subjects in the study in renal impairment (8 per group: normal renal function, moderate renal dysfunction, or end-stage renal disease [ESRD]), and 32 subjects in the study in hepatic impairment (8 per group: normal hepatic function or mild, moderate, or severe hepatic impairment) received a single 150-mg dose of fostamatinib. Patients with ESRD in the study in renal impairment participated in 2 treatment periods separated by a ≥1-week washout. In these patients, fostamatinib was administered after dialysis or 2 hours before dialysis. Geometric mean R406 Cmax and AUC values were less in the combined renally impaired group than in the group with normal renal function; Tmax was similar across groups. However, renal impairment had no apparent effect considered clinically relevant on unbound R406. In patients with ESRD, R406 exposure was less when fostamatinib was administered after compared with before dialysis. Urinary excretion of R406 N-glucuronide was decreased with increasing severity of renal impairment. Renal elimination of R406 was negligible in all groups. Varying degrees of hepatic impairment had no consistent effects on the PK properties of R406. R406 Cmax values were 10% to 15% less in all hepatically impaired groups than in the group with normal hepatic function. AUC and Tmax values were similar between the groups with normal and severely impaired hepatic function; in the groups with mild or moderate hepatic impairment, AUC was less and Tmax was greater. The geometric mean percentage of unbound R406 ranged from 0.64% to 1.95% and was greatest in the group with severe hepatic impairment. The urinary excretion of R406 was minimal. The amount of R406 N-glucuronide excreted in urine was greater in severely hepatically impaired patients. Fostamatinib 150 mg was generally well tolerated. In these patients, renal or hepatic impairment did not affect exposure to the active metabolite of fostamatinib, R406, to a clinically relevant extent. ClinicalTrials.gov identifiers: NCT01245790 (renal) and NCT01222455 (hepatic). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Biomonitoring for Exposure Assessment to Styrene in the Fibreglass Reinforced Plastic Industry: Determinants and Interferents.

PubMed

Bonanni, Rossana Claudia; Gatto, Maria Pia; Paci, Enrico; Gordiani, Andrea; Gherardi, Monica; Tranfo, Giovanna

2015-10-01

Fifty-eight workers exposed to styrene were monitored in four fibreglass reinforced plastic industries of Central Italy. The aim of the study was to explore the factors that can influence the levels of styrene exposure biomarkers of the workers and the aspects that might interfere with the exposure assessment measures, such as the co-exposure to acetone. Personal monitoring of professional exposure to airborne styrene and acetone was carried out by Radiello samplers and GC/MS analysis. Biological monitoring was performed by the determination of urinary metabolites, mandelic (MA), and phenylglyoxylic (PGA) acids with HPLC/MS/MS and unmetabolized styrene in saliva and venous blood by HS/GC/MS. The median values of the four sites ranged between 24.1 to 94.0mg m(-3) and 7.3 to 331.1mg g(-1) creatinine for airborne styrene and MA + PGA, respectively. A good linear correlation was found between styrene in air and its urinary metabolites (r = 0.854). The median value for airborne styrene was found to exceed the (Threshold Limit Value - Time Weighted Average) of 85 mg m(-3) in one site for all the workers and in two if only moulders are considered. The multiple linear regression model showed that the determinants of urinary MA + PGA excretion were the type of process, workers' tasks, level of acetone co-exposure, and the use of respiratory protection devices. Data show that the simultaneous exposure to acetone modify the styrene metabolism with a reduction in the levels of (MA + PGA) excreted. A significant linear log-correlation was found between salivary levels of styrene and blood concentration (r = 0.746) sampled at the same t x time. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults.

PubMed

Wang, Yang; Hu, Jia-Wen; Qu, Peng-Fei; Wang, Ke-Ke; Yan, Yu; Chu, Chao; Zheng, Wen-Ling; Xu, Xian-Jing; Lv, Yong-Bo; Ma, Qiong; Gao, Ke; Yuan, Yue; Li, Hao; Yuan, Zu-Yi; Mu, Jian-Jun

2018-05-17

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

Visual functions of workers exposed to organic solvents in petrochemical industries

PubMed Central

Indhushree, R.; Monica, R.; Coral, K.; Angayarkanni, Narayanasamy; Punitham, R.; Subburathinam, B. M.; Krishnakumar, R.; Santanam, P. P.

2016-01-01

Aim: The purpose of this study was to evaluate the visual functions of workers exposed to organic solvents in petrochemical industries. Materials and Methods: Thirty workers from the petroleum refinery and 30 age-matched controls (mean age) were recruited. Visual functions and occupational exposure levels were assessed among both the groups. Visual acuity, contrast sensitivity, color vision, and visual fields were evaluated at the workplace. The biological samples, namely blood and urine, were collected at the workplace and transported to the laboratory for analysis. The urinary excretion of hippuric and methylhippuric acid as well as creatinine was measured by high performance liquid chromatography. Results: The mean age of the workers and controls were 39.7 ± 7.6 years and 38.6 ± 8.1, years respectively. The mean years of experience of the workers were 15.6 ± 6.8 years. Visual acuity was >0.01 LogMAR among both the control and case groups. The contrast sensitivity was reduced at 12cpd among workers. Comparison between groups was done using independent sample t-test. The mean difference in color confusion index was 0.11 ± 0.05 (P = 0.037*). The mean difference in visual fields was −0.31 ± 0.36 dB (P = 0.933). The mean difference in urinary hippuric acid level (urinary metabolite of toluene) between the groups was 0.19 ± 0.96 g/g creatinine (P = 0.049FNx01). The mean difference in the excretion of methylhippuric acid (urinary metabolite of xylene) was 0.06 ± 0.04g/g creatinine (P = 0.154). We also found that exposure was a significant risk factor for color vision defect with an odds ratio of 4.43 (95% CI: 1.36–14.4); P = 0.013. Conclusion: The study results showed that contrast sensitivity and color vision were affected among workers in petrochemical industry. PMID:28446838

The urinary metabolites of DINCH® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ.

PubMed

Engel, Anika; Buhrke, Thorsten; Kasper, Stefanie; Behr, Anne-Cathrin; Braeuning, Albert; Jessel, Sönke; Seidel, Albrecht; Völkel, Wolfgang; Lampen, Alfonso

2018-05-01

DINCH ® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH ® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH ® , there are almost no toxicological data available regarding its primary and secondary metabolites. The present study aimed at the characterization of potential endocrine properties of DINCH ® and five DINCH ® metabolites by using reporter gene assays to monitor the activity of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ in vitro. DINCH ® itself did not have any effect on the activity of these receptors whereas DINCH ® metabolites were shown to activate all these receptors. In the case of AR, DINCH ® metabolites predominantly enhanced dihydrotestosterone-stimulated AR activity. In the H295R steroidogenesis assay, neither DINCH ® nor any of its metabolites affected estradiol or testosterone synthesis. In conclusion, primary and secondary DINCH ® metabolites exert different effects at the molecular level compared to DINCH ® itself. All these in vitro effects of DINCH ® metabolites, however, were only observed at high concentrations such as 10 μM or above which is about three orders of magnitude above reported DINCH ® metabolite concentrations in human urine. Thus, the in vitro data do not support the notion that DINCH ® or any of the investigated metabolites may exert considerable endocrine effects in vivo at relevant human exposure levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous analysis of naphthols, phenanthrols, and 1-hydroxypyrene in urine as biomarkers of polycyclic aromatic hydrocarbon exposure: intraindividual variance in the urinary metabolite excretion profiles caused by intervention with beta-naphthoflavone induction in the rat.

PubMed

Elovaara, Eivor; Väänänen, Virpi; Mikkola, Jouni

2003-04-01

Two fluorimetric HPLC methods are described for the quantification of naphthols, phenanthrols and 1-hydroxypyrene (1-OHP) in urine specimens obtained from male Wistar rats exposed to naphthalene, phenanthrene and pyrene. The polycyclic aromatic hydrocarbons (PAHs) were given intraperitoneally, either alone (1.0 mmol/kg body weight) or as an equimolar mixture (0.33 mmol/kg), using the same dosages for repeated treatments on week 1 and week 2. Between these treatments, PAH-metabolizing activities encoded by aryl hydrocarbon (Ah) receptor-controlled genes were induced in the rats with beta-naphthoflavone (betaNF). Chromatographic separation of five phenanthrols (1-, 2-, 3-, 4-, and 9-isomers) was accomplished using two different RP C-18 columns. Despite selective detection (programmable wavelengths), the quantification limits in the urine ranged widely: 1-OHP (0.18 microg/l)

Reproducibility of urinary biomarkers in multiple 24-h urine samples.

PubMed

Sun, Qi; Bertrand, Kimberly A; Franke, Adrian A; Rosner, Bernard; Curhan, Gary C; Willett, Walter C

2017-01-01

Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies. We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples. We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses' Health Study), NHSII (Nurses' Health Study II), and Health Professionals Follow-Up Study. In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to ≥1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs >0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally ≤0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of ≥0.8 with true long-term urinary excretion. These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or ≤1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies. © 2017 American Society for Nutrition.

Reproducibility of urinary biomarkers in multiple 24-h urine samples123

PubMed Central

Sun, Qi; Bertrand, Kimberly A; Franke, Adrian A; Rosner, Bernard; Curhan, Gary C; Willett, Walter C

2017-01-01

Background: Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies. Objective: We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples. Design: We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses’ Health Study), NHSII (Nurses’ Health Study II), and Health Professionals Follow-Up Study. Results: In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to ≥1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs >0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally ≤0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of ≥0.8 with true long-term urinary excretion. Conclusions: These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or ≤1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies. PMID:28049663

Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation.

PubMed

Lieske, John C; Tremaine, William J; De Simone, Claudio; O'Connor, Helen M; Li, Xujian; Bergstralh, Eric J; Goldfarb, David S

2010-12-01

We examined the effect of a controlled diet and two probiotic preparations on urinary oxalate excretion, a risk factor for calcium oxalate kidney stone formation, in patients with mild hyperoxaluria. Patients were randomized to a placebo, a probiotic, or a synbiotic preparation. This tested whether these probiotic preparations can increase oxalate metabolism in the intestine and/or decrease oxalate absorption from the gut. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake from food. Urinary oxalate excretion and calcium oxalate supersaturation on the controlled diet were significantly lower compared with baseline on a free-choice diet. Neither study preparation reduced urinary oxalate excretion nor calcium oxalate supersaturation. Fecal lactobacilli colony counts increased on both preparations, whereas enterococcal and yeast colony counts were increased on the synbiotic. Total urine volume and the excretion of oxalate and calcium were all strong independent determinants of urinary calcium oxalate supersaturation. Hence, dietary oxalate restriction reduced urinary oxalate excretion, but the tested probiotics did not influence urinary oxalate levels in patients on a restricted oxalate diet. However, this study suggests that dietary oxalate restriction is useful for kidney stone prevention.

Excretion Profiles and Half-Lives of Ten Urinary Polycyclic Aromatic Hydrocarbon Metabolites after Dietary Exposure

PubMed Central

Li, Zheng; Romanoff, Lovisa; Bartell, Scott; Pittman, Erin N.; Trinidad, Debra A.; McClean, Michael; Webster, Thomas F.; Sjödin, Andreas

2015-01-01

Human exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed by biomonitoring of their urinary mono-hydroxylated metabolites (OH-PAHs). Limited information exists on the human pharmacokinetics of OH-PAHs. This study aimed to investigate the excretion half-life of 1-hydroxypyrene (1-PYR), the most used biomarker for PAH exposure, and 9 other OH-PAHs following a dietary exposure in 9 non-smoking volunteers with no occupational exposure to PAHs. Each person avoided food with known high PAH-content during the study period, except for a high PAH-containing lunch (barbecued chicken) on the first day. Individual urine samples (n = 217) were collected from 15 hours before to 60 hours following the dietary exposure. Levels of all OH-PAHs in all subjects increased rapidly by 9–141 fold after the exposure, followed by a decrease consistent with first order kinetics, and returned to background levels 24–48 hours after the exposure. The average time to reach maximal concentration ranged from 3.1 h (1-naphthol) to 5.5 h (1-PYR). Creatinine-adjusted urine concentrations for each metabolite were analyzed using a non-linear mixed effects model including a term to estimate background exposure. The background-adjusted half-life estimate was 3.9 h for 1-PYR and ranged 2.5–6.1 h for the other 9 OH-PAHs, which in general, were shorter than those previously reported. The maximum concentrations after the barbecued chicken consumption were comparable to the levels found in reported occupational settings with known high PAH exposures. It is essential to consider the relatively short half-life, the timing of samples relative to exposures, and the effect of diet when conducting PAH exposure biomonitoring studies. PMID:22663094

Detection and characterization of urinary metabolites of boldione by LC-MS/MS. Part I: Phase I metabolites excreted free, as glucuronide and sulfate conjugates, and released after alkaline treatment of the urine.

PubMed

Gómez, C; Pozo, O J; Fabregat, A; Marcos, J; Deventer, K; Van Eenoo, P; Segura, J; Ventura, R

2012-10-01

Boldione (1,4-androstadien-3,17-dione) is included in the list of prohibited substances, issued by the World Anti-Doping Agency (WADA). Endogenous production of low concentrations of boldione has also been reported. The objective of this study was to assess boldione metabolism in humans. Detection of boldione metabolites was accomplished by analysis by liquid chromatography coupled to tandem mass spectrometry of urine samples obtained after administration of the drug and subjected to different sample preparation procedures to analyze the different metabolic fractions (free, glucuronides, sulpfates and released in basic media). In addition to boldione, eight metabolites were detected in the free fraction. Four of them were identified by comparison with standards: 6β-hydroxy-boldenone (M3), androsta-1,4,6-triene-3,17-dione (M5), (5α)-1-androstenedione (M6) and (5α)-1-testosterone (M8). Metabolite M7 was identified as the 5β-isomer of 1-androstenedione, and metabolites M1, M2 and M4 were hydroxylated metabolites and tentative structures were proposed based on mass spectrometric data. After β-glucuronidase hydrolysis, five additional metabolites excreted only as conjugates with glucuronic acid were detected: boldenone, (5β)-1-testosterone (M9), and three metabolites resulting from reduction of the 3-keto group. Boldenone, epiboldenone, and hydroxylated metabolites of boldione, boldenone and 1-testosterone were detected as conjugates with sulfate. In addition, boldione and seven metabolites (boldenone, M2, M3, M4, M5, M7 and M9) increased their concentration in urine after treatment of the urine in alkaline conditions. In summary, 15 boldione metabolites were detected in all fractions. The longer detection time was observed for metabolite M4 after alkaline treatment of the urine, which was detected up to 5 days after boldione administration. Copyright © 2012 John Wiley & Sons, Ltd.

Oxybuprocaine and five metabolites simultaneously determined in urine by gas chromatography and gas chromatography-mass spectrometry after extraction with Extrelut.

PubMed

Kasuya, F; Igarashi, K; Fukui, M

1987-05-01

We describe a gas-liquid chromatographic (GC) method for determination of oxybuprocaine, and a gas chromatographic-mass spectrometric (GC-MS) method for simultaneous determination of four of its nine metabolites in urine. We used an Extrelut column to simply and rapidly extract oxybuprocaine and its metabolites from urine. For the GC-MS analyses, we monitored the characteristic fragment ions at m/z 353, 395, 369, 411, and 235 for 3-butoxy-4-aminobenzoic acid (metabolite 2, M-2), 3-butoxy-4-acetylaminobenzoic acid (M-3), 3-hydroxy-4-aminobenzoic acid (M-4), 3-hydroxy-4-acetylaminobenzoic acid (M-5), and methaqualone (internal standard), respectively. We quantified the glucuronide of M-2 after enzymic treatment. The assay's selectivity and reproducibility (within-day and between-day CVs less than 8% for all metabolites) make it applicable to determine oxybuprocaine and its metabolites in human urine. Mean 9-h urinary excretion of oxybuprocaine and its five metabolites from four healthy volunteers was 89.2% after a 100-mg oral dose.

Down-regulation of a hepatic transporter multidrug resistance-associated protein 2 is involved in alteration of pharmacokinetics of glycyrrhizin and its metabolites in a rat model of chronic liver injury.

PubMed

Makino, Toshiaki; Ohtake, Nobuhiro; Watanabe, Akito; Tsuchiya, Naoko; Imamura, Sachiko; Iizuka, Seiichi; Inoue, Makoto; Mizukami, Hajime

2008-07-01

Glycyrrhizin (GL) has been used to treat chronic hepatitis in Japan and Europe. It is thought to induce pseudoaldosteronism via inhibition of type 2 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) by glycyrrhetinic acid (GA), a major metabolite of GL. A previous clinical study suggested that 3-monoglucuronyl-glycyrrhetinic acid (3MGA), another metabolite of GL, might play a more important role in the pathogenesis of pseudoaldosteronism. The present study evaluates the pharmacokinetics of GL and its metabolites in rats with chronic liver injury induced by a choline-deficient l-amino acid-defined (CDAA) diet to clarify the relationship between 3MGA and pseudoaldosteronism. In rats fed a CDAA diet, plasma concentrations and urinary eliminations of GL and 3MGA were markedly higher than in the rats fed the control diet; the plasma concentration of GA was unaffected when GL was orally administered. Immunohistochemical analysis revealed the suppression of levels of multidrug resistance-associated protein (Mrp) 2 and its localization in the hepatic tissue of rats fed a CDAA diet. When 3MGA was i.v. injected in rats fed a CDAA diet or injected in Mrp2-dysfunctional Eisai hyperbilirubinemic rats, plasma concentrations of 3MGA were higher, and biliary excretion of 3MGA was lower than in each control group. The results suggested that 3MGA would be excreted to bile via hepatic Mrp2 and that its dysfunction would reduce 3MGA clearance. 3MGA accumulated by liver fibrosis resulted in the increased excretion through renal tubule and might be strongly related to the pathogenesis of pseudoaldosteronism because 11beta-HSD2 is expressed in renal tubular epithelial cells.

Developmental outcome of levetiracetam, its major metabolite in humans, 2-pyrrolidinone N-butyric acid, and its enantiomer (R)-alpha-ethyl-oxo-pyrrolidine acetamide in a mouse model of teratogenicity.

PubMed

Isoherranen, Nina; Spiegelstein, Ofer; Bialer, Meir; Zhang, Jing; Merriweather, Michelle; Yagen, Boris; Roeder, Michael; Triplett, Aleata A; Schurig, Volker; Finnell, Richard H

2003-10-01

The purpose of this study was to test the teratogenic potential of the antiepileptic drug (AED) levetiracetam (LEV), its major metabolite in humans, 2-pyrrolidone-N-butyric acid (PBA), and enantiomer, (R)-alpha-ethyl-oxo-pyrrolidine acetamide (REV), in a well-established mouse model. All compounds were administered by intraperitoneal injections once daily to SWV/Fnn mice on gestational days 8-1/2 to 12-1/2. LEV was administered at doses of 600, 1,200, and 2,000 mg/kg/day, piracetam (PIR) and PBA, at 600 and 1,200 mg/kg/day, and REV, at 600 mg/kg/day. On gestational day 18(1/2), fetuses were examined for gross external malformations and prepared for skeletal analysis by using Alizarin Red S staining. No significant gross external malformations were observed in any of the study groups. Fetal weights were significantly reduced in most study groups. Resorption rates were significantly increased only in the 2,000-mg/kg/day LEV group. The overall incidence of skeletal abnormalities and specifically of hypoplastic phalanges was significantly increased in both PBA treatments and in the intermediate 1,200-mg/kg/day LEV group. In contrast to that in humans, 24-h urinary excretion analysis in mice showed that 65-100% of the LEV doses were excreted unchanged, whereas only 4% was excreted as the metabolite PBA. Results of this study demonstrate that both LEV and its major metabolite in humans, PBA, do not induce major structural malformations in developing SWV/Fnn embryos and suggest that they provide a margin of reproductive safety for the pregnant epileptic population when compared with other AEDs tested in this mouse model.

Disposition and biotransformation of the acetylenic retinoid tazarotene in humans.

PubMed

Attar, Mayssa; Yu, Dale; Ni, Jinsong; Yu, Zhiling; Ling, Kah-Hiing John; Tang-Liu, Diane D-S

2005-10-01

Oral tazarotene, an acetylenic retinoid, is in clinical development for the treatment of psoriasis. The disposition and biotransformation of tazarotene were investigated in six healthy male volunteers, following a single oral administration of a 6 mg (100 microCi) dose of [14C]tazarotene, in a gelatin capsule. Blood levels of radioactivity peaked 2 h postdose and then rapidly declined. Total recovery of radioactivity was 89.2+/-8.0% of the administered dose, with 26.1+/-4.2% in urine and 63.0+/-7.0% in feces, within 7 days of dosing. Only tazarotenic acid, the principle active metabolite formed via esterase hydrolysis of tazarotene, was detected in blood. One major urinary oxidative metabolite, tazarotenic acid sulfoxide, accounted for 19.2+/-3.0% of the dose. The majority of radioactivity recovered in the feces was attributed to tazarotenic acid representing 46.9+/-9.9% of the dose and only 5.82+/-3.84% of dose was excreted as unchanged tazarotene. Thus following oral administration, tazarotene was rapidly absorbed and underwent extensive hydrolysis to tazarotenic acid, the major circulating species in the blood that was then excreted unchanged in feces. A smaller fraction of tazarotenic acid was further metabolized to an inactive sulfoxide that was excreted in the urine. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease.

PubMed

Torres, Vicente E; Abebe, Kaleab Z; Schrier, Robert W; Perrone, Ronald D; Chapman, Arlene B; Yu, Alan S; Braun, William E; Steinman, Theodore I; Brosnahan, Godela; Hogan, Marie C; Rahbari, Frederic F; Grantham, Jared J; Bae, Kyongtae T; Moore, Charity G; Flessner, Michael F

2017-02-01

The CRISP study of polycystic kidney disease (PKD) found that urinary sodium excretion associated with the rate of total kidney volume increase. Whether sodium restriction slows the progression of Autosomal Dominant PKD (ADPKD) is not known. To evaluate this we conducted a post hoc analysis of the HALT-PKD clinical trials of renin-angiotensin blockade in patients with ADPKD. Linear mixed models examined whether dietary sodium affected rates of total kidney volume or change in estimated glomerular filtration rate (eGFR) in patients with an eGFR over 60 ml/min/1.73 m 2 (Study A) or the risk for a composite endpoint of 50% reduction in eGFR, end-stage renal disease or death, or the rate of eGFR decline in patients with an eGFR 25-60 ml/min/1.73 m 2 (Study B) all in patients initiated on an under100 mEq sodium diet. During the trial urinary sodium excretion significantly declined by an average of 0.25 and 0.41 mEq/24 hour per month in studies A and B, respectively. In Study A, averaged and time varying urinary sodium excretions were significantly associated with kidney growth (0.43%/year and 0.09%/year, respectively, for each 18 mEq urinary sodium excretion). Averaged urinary sodium excretion was not significantly associated with faster eGFR decline (-0.07 ml/min/1.73m 2 /year for each 18 mEq urinary sodium excretion). In Study B, the averaged but not time-varying urinary sodium excretion significantly associated with increased risk for the composite endpoint (hazard ratio 1.08 for each 18 mEq urinary sodium excretion) and a significantly faster eGFR decline (-0.09 ml/min/1.73m 2 /year for each mEq 18 mEq urinary sodium excretion). Thus, sodium restriction is beneficial in the management of ADPKD. Copyright © 2016 International Society of Nephrology. All rights reserved.

Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in Chinese Adults

PubMed Central

Peng, Yaguang; Li, Wei; Wang, Yang; Chen, Hui; Bo, Jian; Wang, Xingyu; Liu, Lisheng

2016-01-01

24-h urinary sodium excretion is the gold standard for evaluating dietary sodium intake, but it is often not feasible in large epidemiological studies due to high participant burden and cost. Three methods—Kawasaki, INTERSALT, and Tanaka—have been proposed to estimate 24-h urinary sodium excretion from a spot urine sample, but these methods have not been validated in the general Chinese population. This aim of this study was to assess the validity of three methods for estimating 24-h urinary sodium excretion using spot urine samples against measured 24-h urinary sodium excretion in a Chinese sample population. Data are from a substudy of the Prospective Urban Rural Epidemiology (PURE) study that enrolled 120 participants aged 35 to 70 years and collected their morning fasting urine and 24-h urine specimens. Bias calculations (estimated values minus measured values) and Bland-Altman plots were used to assess the validity of the three estimation methods. 116 participants were included in the final analysis. Mean bias for the Kawasaki method was -740 mg/day (95% CI: -1219, 262 mg/day), and was the lowest among the three methods. Mean bias for the Tanaka method was -2305 mg/day (95% CI: -2735, 1875 mg/day). Mean bias for the INTERSALT method was -2797 mg/day (95% CI: -3245, 2349 mg/day), and was the highest of the three methods. Bland-Altman plots indicated that all three methods underestimated 24-h urinary sodium excretion. The Kawasaki, INTERSALT and Tanaka methods for estimation of 24-h urinary sodium excretion using spot urines all underestimated true 24-h urinary sodium excretion in this sample of Chinese adults. Among the three methods, the Kawasaki method was least biased, but was still relatively inaccurate. A more accurate method is needed to estimate the 24-h urinary sodium excretion from spot urine for assessment of dietary sodium intake in China. PMID:26895296

Determinants of Brushite Stone Formation: A Case-Control Study

PubMed Central

Siener, Roswitha; Netzer, Linda; Hesse, Albrecht

2013-01-01

Purpose The occurrence of brushite stones has increased during recent years. However, the pathogenic factors driving the development of brushite stones remain unclear. Methods Twenty-eight brushite stone formers and 28 age-, sex- and BMI-matched healthy individuals were enrolled in this case-control study. Anthropometric, clinical, 24 h urinary parameters and dietary intake from 7-day weighed food records were assessed. Results Pure brushite stones were present in 46% of patients, while calcium oxalate was the major secondary stone component. Urinary pH and oxalate excretion were significantly higher, whereas urinary citrate was lower in patients as compared to healthy controls. Despite lower dietary intake, urinary calcium excretion was significantly higher in brushite stone patients. Binary logistic regression analysis revealed pH>6.50 (OR 7.296; p = 0.035), calcium>6.40 mmol/24 h (OR 25.213; p = 0.001) and citrate excretion <2.600 mmol/24 h (OR 15.352; p = 0.005) as urinary risk factors for brushite stone formation. A total of 56% of patients exhibited distal renal tubular acidosis (dRTA). Urinary pH, calcium and citrate excretion did not significantly differ between patients with or without dRTA. Conclusions Hypercalciuria, a diminished citrate excretion and an elevated pH turned out to be the major urinary determinants of brushite stone formation. Interestingly, urinary phosphate was not associated with urolithiasis. The increased urinary oxalate excretion, possibly due to decreased calcium intake, promotes the risk of mixed stone formation with calcium oxalate. Neither dietary factors nor dRTA can account as cause for hypercalciuria, higher urinary pH and diminished citrate excretion. Further research is needed to define the role of dRTA in brushite stone formation and to evaluate the hypothesis of an acquired acidification defect. PMID:24265740

Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality

PubMed Central

Raffler, Johannes; Friedrich, Nele; Arnold, Matthias; Kacprowski, Tim; Rueedi, Rico; Altmaier, Elisabeth; Bergmann, Sven; Budde, Kathrin; Gieger, Christian; Homuth, Georg; Pietzner, Maik; Römisch-Margl, Werner; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wallaschofski, Henri; Nauck, Matthias; Völker, Uwe; Kastenmüller, Gabi; Suhre, Karsten

2015-01-01

Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo-inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. PMID:26352407

Urinary excretion of platinum from South African precious metals refinery workers.

PubMed

Linde, Stephanus J L; Franken, Anja; du Plessis, Johannes L

2018-03-30

Urinary platinum (Pt) excretion is a reliable biomarker for occupational Pt exposure and has been previously reported for precious metals refinery workers in Europe but not for South Africa, the world's largest producer of Pt. This study aimed to quantify the urinary Pt excretion of South African precious metals refinery workers. Spot urine samples were collected from 40 workers (directly and indirectly exposed to Pt) at two South African precious metals refineries on three consecutive mornings prior to their shifts. Urine samples were analysed for Pt using inductively coupled plasma-mass spectrometry and were corrected for creatinine content. The urinary Pt excretion of workers did not differ significantly between sampling days. Urinary Pt excretions ranged from <0.1 to 3.0 µg Pt/g creatinine with a geometric mean of 0.21 µg Pt/g creatinine (95% CI 0.17 to 0.26 µg Pt/g creatinine). The work area (P=0.0006; η 2 =0.567) and the number of years workers were employed at the refineries (P=0.003; η 2 =0.261) influenced their urinary Pt excretion according to effect size analyses. Directly exposed workers had significantly higher urinary Pt excretion compared with indirectly exposed workers (P=0.007). The urinary Pt excretion of South African precious metals refinery workers reported in this study is comparable with that of seven other studies conducted in precious metals refineries and automotive catalyst plants in Europe. The Pt body burden of workers is predominantly determined by their work area, years of employment in the refineries and whether they are directly or indirectly exposed to Pt. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of dosage increments on blood phenytoin concentrations

PubMed Central

Bochner, F.; Hooper, W. D.; Tyrer, J. H.; Eadie, M. J.

1972-01-01

Blood phenytoin (diphenylhydantoin) concentrations were measured after each dosage change in 12 epileptic patients who were given increasing oral doses of phenytoin. In each of these patients a dosage increment beyond the dosage that produced a blood phenytoin level of 6-9 μg/ml. caused a disproportionately great increase in the blood concentration of drug. This effect might be expected if the limit of the body's capacity to metabolize phenytoin were being reached. As oral dosages were increased in one patient, measurements of the rate of urinary excretion of phenytoin metabolite showed that the phase of rapid rise in blood phenytoin concentration coincided with a failure to increase the rate of phenytoin metabolite excretion. Awareness of the non-linear relation between oral dose and blood concentration of phenytoin in the individual patient, and realization that the phase of rapid rise in blood phenytoin concentration occurs through the `therapeutic' range of 10-20 μg/ml., is of importance to those who use blood phenytoin levels as a guide to the adequacy of anticonvulsant therapy. PMID:4647859

On-pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens.

PubMed

Cavalca, V; Rocca, B; Veglia, F; Petrucci, G; Porro, B; Myasoedova, V; De Cristofaro, R; Turnu, L; Bonomi, A; Songia, P; Cavallotti, L; Zanobini, M; Camera, M; Alamanni, F; Parolari, A; Patrono, C; Tremoli, E

2017-11-01

On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100 mg once-daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once-daily, 100 mg twice-daily, or 200 mg once-daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once-daily showed a significant increase in serum thromboxane (TX)B 2 within the 24-hour dosing interval and urinary TXA 2 metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB 2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin-angiotensin-aldosterone system activity and the efficacy of renin-angiotensin-aldosterone system blockade in the kidney.

PubMed

van den Heuvel, Mieke; Batenburg, Wendy W; Jainandunsing, Sjaam; Garrelds, Ingrid M; van Gool, Jeanette M G; Feelders, Richard A; van den Meiracker, Anton H; Danser, A H Jan

2011-11-01

To study which renin-angiotensin-aldosterone system (RAAS) component best reflects renal RAAS activity. We measured urinary and plasma renin, prorenin, angiotensinogen, aldosterone, albumin and creatinine in 101 diabetic and nondiabetic patients with or without hypertension. Plasma prorenin was elevated in diabetic patients. Urinary prorenin was undetectable. Urinary albumin and renin were higher in diabetic patients. Men had higher plasma renin/prorenin levels, and lower plasma angiotensinogen levels than women. Plasma creatinine and albumin were also higher in men. Urinary RAAS components showed no sexual dimorphism, whereas urinary creatinine and albumin were higher in men. Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers increased plasma renin and decreased plasma angiotensinogen, without altering plasma aldosterone. In contrast, in urine, these drugs decreased renin and aldosterone without affecting angiotensinogen. When analyzing all patients together, urinary angiotensinogen excretion closely mimicked that of albumin, whereas urinary angiotensinogen and albumin levels both were 0.05% or less of their concomitant plasma levels. This may reflect the identical glomerular filtration and tubular handling of both proteins, which have a comparable molecular weight. In contrast, urinary renin excretion did not correlate with urinary albumin excretion, and the urinary/plasma concentration ratio of renin was more than 200 times the ratio of albumin, despite its comparable molecular weight. Urinary aldosterone excretion closely followed urinary creatinine excretion. The increased urinary renin levels in diabetes and the decreased urinary renin levels following RAAS blockade, occurring independently of changes in plasma renin, reflect the activated renal RAAS in diabetes and the success of RAAS blockade in the kidney, respectively. Urinary renin, therefore, more closely reflects renal RAAS activity than urinary angiotensinogen or aldosterone.

Studies on absorption and elimination of dietary maillard reaction products.

PubMed

Förster, Anke; Kühne, Yvonne; Henle, Thomas

2005-06-01

A nine-day dietary study involving 18 healthy volunteers was performed in order to investigate the influence of nutrition on the urinary excretion of the Maillard reaction products (MRPs) fructoselysine, pyrraline, and pentosidine. From day two through day eight, most types of Maillard product-containing food had to be avoided. On day five, participants were divided into four groups, three of them receiving a test meal (pretzel sticks, brewed coffee, or custard) containing defined amounts of MRPs. The fourth group served as a control. Urine samples taken over a 24-h period were analyzed for MRPs using chromatographic means. As a result of the MRP-free diet, urinary excretion of free pyrraline and fructoselysine, which was calculated from furosine analysis, were lowered about 90%. Excretion of pentosidine decreased about 40%. Consumption of pretzel sticks and coffee on day five resulted in increased amounts of pyrraline and pentosidine in urine samples on days five to seven. Related to the supplied amounts of pyrraline, about 50% were recovered in the urine samples after ingestion of the pretzel sticks. For pentosidine, 60% of the ingested free derivative from coffee brew and 2% of the peptide-bound amino acid ingested with the bakery product were recovered in the urine samples, indicating a better bioavailability for free pentosidine compared to the protein-bound form. For peptide-bound Amadori products, no influence on the excretion was observed after ingestion of the test foods, indicating degradation in the intestine or plasma to yet-unknown metabolites. In conclusion, differences concerning the excretion rate of individual MRPs point to individual resorption and metabolic pathways. These results are of importance for the discussion of a possible (patho)physiological role of dietary advanced glycation end products (AGEs).

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Limpatanachote, Pisit

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinarymore » excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population. - Research highlights: {yields} Excessive calciuria is the major risk of urinary stone formation. {yields} We examine cadmium-exposed persons for urinary cadmium, calcium, and stones. {yields} The rate of urinary stones increases with increasing urinary cadmium. {yields} Urinary calcium excretion increases with increasing urinary cadmium. {yields} Elevated calciuria induced by cadmium may increase the risk of urinary stones.« less

LY3127760, a Selective Prostaglandin E4 (EP4) Receptor Antagonist, and Celecoxib: A Comparison of Pharmacological Profiles.

PubMed

Jin, Yan; Smith, Claire; Hu, Leijun; Coutant, David E; Whitehurst, Kelly; Phipps, Krista; McNearney, Terry Ann; Yang, Xiao; Ackermann, Bradley; Pottanat, Thomas; Landschulz, William

2018-01-01

Safety, tolerability, and pharmacology profiles of LY3127760, an EP4 antagonist, were explored in healthy subjects in a subject/investigator-blind, parallel-group, multiple-ascending dose study. Cohorts consisted of 13 patients randomized to LY3127760, celecoxib (400 mg), or placebo (9:2:2 ratio) for 28 days. LY3127760 was well tolerated; the most commonly observed adverse events were gastrointestinal, similar to celecoxib. LY3127760 increased release of ex vivo tumor necrosis factor alpha after lipopolysaccharide/prostaglandin E2 stimulation when compared with placebo, suggesting a dose-dependent blockade of the EP4 receptor. Compared with placebo, 24-h urinary excretion of prostaglandin E metabolite was modestly increased; prostacyclin metabolite was inhibited; and thromboxane A2 metabolite was unchanged. Effects on sodium and potassium excretion were similar to those of celecoxib. We conclude that LY3127760 demonstrated similar effects on prostacyclin synthesis and renal sodium retention as celecoxib. These data support exploration of LY3127760 at daily doses of 60 mg to 600 mg in phase II trials. This trial's registration number: NCT01968070. © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Recent developments in urinalysis of metabolites of new psychoactive substances using LC-MS.

PubMed

Peters, Frank T

2014-08-01

In the last decade, an ever-increasing number of new psychoactive substances (NPSs) have appeared on the recreational drug market. To account for this development, analytical toxicologists have to continuously adapt their methods to encompass the latest NPSs. Urine is the preferred biological matrix for screening analysis in different areas of analytical toxicology. However, the development of urinalysis procedures for NPSs is complicated by the fact that generally little or no information on urinary excretion patterns of such drugs exists when they first appear on the market. Metabolism studies are therefore a prerequisite in the development of urinalysis methods for NPSs. In this article, the literature on the urinalysis of NPS metabolites will be reviewed, focusing on articles published after 2008.

Application of Liquid Chromatography-Tandem Mass Spectrometry To Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes?

PubMed

Logue, Caomhan; Dowey, Le Roy C; Strain, J J; Verhagen, Hans; McClean, Stephen; Gallagher, Alison M

2017-06-07

Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10-1000 ng/mL with coefficients of determination ranging from 0.9969 to 0.9997. Accuracy ranged from 92 to 104%, and intrabatch and interday precisions were within acceptable limits with %CV below 8% for all compounds. A double-blind, randomized crossover dose-response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes of sampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p < 0.001), whereas for sucralose, urinary concentrations were useful for distinguishing between low (0.1% ADI) and high doses (10% ADI) only (p < 0.001). In summary, this biomarker approach may be useful for assessing intakes of five commonly consumed LCSs.

Objective assessment of smoking habits by urinary cotinine measurement in adolescents and young adults with type 1 diabetes. Reliability of reported cigarette consumption and relationship to urinary albumin excretion.

PubMed

Holl, R W; Grabert, M; Heinze, E; Debatin, K M

1998-05-01

To examine the relationship of objective smoking status to age, sex, longterm metabolic control, and urinary albumin excretion. Patients with type 1 diabetes who smoke are at increased risk to develop diabetic microvascular and macrovascular complications. While this has repeatedly been demonstrated in adults, smoking habits have rarely been investigated in adolescents. Urinary continine excretion has been determined by radioimmunoassay in 238 adolescents and young adults with type 1 diabetes. This biochemical parameter of nicotine use was related to age, to the number of cigarettes allegedly consumed per day, and to urinary albumin excretion. A total of 46 patients (19.3%) with urinary cotinine values > 500 ng/ml were classified as smokers. In 26 patients (10.9%), cotinine values between 100 and 500 ng/ml were found (infrequent smokers or environmental nicotine exposure), while the remaining 166 patients excreted < 100 ng/ml of cotinine in the urine (nonsmokers). Smokers were significantly older (20.2 +/- 0.6 years [mean +/- SE]) compared with the intermediate group (18.3 +/- 0.7 years) or with nonsmokers (15.9 +/- 0.4 years; P < 0.0001, Wilcoxon's signed-rank test). Of 46 smokers, 12 denied smoking cigarettes entirely, and among biochemically defined smokers, no correlation was present between urinary continine excretion and the reported number of cigarettes consumed per day. Urinary albumin excretion was significantly higher in smokers compared with nonsmokers (P < 0.003). These data demonstrate that cigarette smoking is common among German adolescents and young adults with type 1 diabetes in this study. Many patients deny nicotine use or refuse to disclose their smoking habits. Increased urinary albumin excretion is consistent with an increased risk of nephropathy in subjects with diabetes who smoke. Pediatricians in charge of adolescents with type 1 diabetes should actively discuss the risk of nicotine consumption with their patients.

The urinary excretion of metformin, ceftizoxime and ofloxacin in high serum creatinine rats: Can creatinine predict renal tubular elimination?

PubMed

Ma, Yan-Rong; Zhou, Yan; Huang, Jing; Qin, Hong-Yan; Wang, Pei; Wu, Xin-An

2018-03-01

The renal excretion of creatinine and most drugs are the net result of glomerular filtration and tubular secretion, and their tubular secretions are mediated by individual transporters. Thus, we hypothesized that the increase of serum creatinine (SCr) levels attributing to inhibiting tubular transporters but not glomerular filtration rate (GFR) could be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine. In this work, we firstly developed the creatinine excretion inhibition model with normal GFR by competitively inhibiting tubular transporters, and investigated the renal excretion of metformin, ceftizoxime and ofloxacin in vivo and in vitro. The results showed that the 24-hour urinary excretion of metformin and ceftizoxime in model rats were decreased by 25% and 17% compared to that in control rats, respectively. The uptake amount and urinary excretion of metformin and ceftizoxime could be inhibited by creatinine in renal cortical slices and isolated kidney perfusion. However, the urinary excretion of ofloxacin was not affected by high SCr. These results showed that the inhibition of tubular creatinine transporters by high SCr resulted to the decrease of urinary excretion of metformin and ceftizoxime, but not ofloxacin, which implied that the increase of SCr could also be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine in normal GFR rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Genetic African Ancestry and Markers of Mineral Metabolism in CKD

PubMed Central

Parsa, Afshin; Isakova, Tamara; Scialla, Julia J.; Chen, Jing; Flack, John M.; Nessel, Lisa C.; Gupta, Jayanta; Bellovich, Keith A.; Steigerwalt, Susan; Sondheimer, James H.; Wright, Jackson T.; Feldman, Harold I.; Kusek, John W.; Lash, James P.; Wolf, Myles

2016-01-01

Background and objectives Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. Design, setting, participants, & measurements In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Results Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). Conclusions A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic variability might contribute to racial differences in urinary phosphorus excretion in CKD. PMID:26912553

Genetic African Ancestry and Markers of Mineral Metabolism in CKD.

PubMed

Gutiérrez, Orlando M; Parsa, Afshin; Isakova, Tamara; Scialla, Julia J; Chen, Jing; Flack, John M; Nessel, Lisa C; Gupta, Jayanta; Bellovich, Keith A; Steigerwalt, Susan; Sondheimer, James H; Wright, Jackson T; Feldman, Harold I; Kusek, John W; Lash, James P; Wolf, Myles

2016-04-07

Disorders of mineral metabolism are more common in African Americans with CKD than in European Americans with CKD. Previous studies have focused on the differences in mineral metabolism by self-reported race, making it difficult to delineate the importance of environmental compared with biologic factors. In a cross-sectional analysis of 3013 participants of the Chronic Renal Insufficiency Cohort study with complete data, we compared markers of mineral metabolism (phosphorus, calcium, alkaline phosphatase, parathyroid hormone, fibroblast growth factor 23, and urine calcium and phosphorus excretion) in European Americans versus African Americans and separately, across quartiles of genetic African ancestry in African Americans (n=1490). Compared with European Americans, African Americans had higher blood concentrations of phosphorus, alkaline phosphatase, fibroblast growth factor 23, and parathyroid hormone, lower 24-hour urinary excretion of calcium and phosphorus, and lower urinary fractional excretion of calcium and phosphorus at baseline (P<0.001 for all). Among African Americans, a higher percentage of African ancestry was associated with lower 24-hour urinary excretion of phosphorus (Ptrend<0.01) in unadjusted analyses. In linear regression models adjusted for socio-demographic characteristics, kidney function, serum phosphorus, and dietary phosphorus intake, higher percentage of African ancestry was significantly associated with lower 24-hour urinary phosphorus excretion (each 10% higher African ancestry was associated with 39.6 mg lower 24-hour urinary phosphorus, P<0.001) and fractional excretion of phosphorus (each 10% higher African ancestry was associated with an absolute 1.1% lower fractional excretion of phosphorus, P=0.01). A higher percentage of African ancestry was independently associated with lower 24-hour urinary phosphorus excretion and lower fractional excretion of phosphorus among African Americans with CKD. These findings suggest that genetic variability might contribute to racial differences in urinary phosphorus excretion in CKD. Copyright © 2016 by the American Society of Nephrology.

Documenting the kinetic time course of lambda-cyhalothrin metabolites in orally exposed volunteers for the interpretation of biomonitoring data.

PubMed

Khemiri, Rania; Côté, Jonathan; Fetoui, Hamadi; Bouchard, Michèle

2017-07-05

Lambda-cyhalothrin is a pyrethroid pesticide largely used in agriculture. Exposure assessment can be performed by measuring key urinary metabolites. For a proper use of biomonitoring data, it is however important to gain information on the toxicokinetics of these key biomarkers of exposure. A human volunteer study was performed to document the plasma and urinary time courses of major lambda-cyhalothrin metabolites. Seven volunteers ingested 0.025mgkg -1 body weight of lambda-cyhalothrin. Blood samples were withdrawn prior to dosing and at fixed time periods over the 72 h-period following ingestion and complete urine voids were collected pre-exposure and at pre-established intervals over 84h post-dosing. The cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were quantified in these samples. Plasma concentrations of CFMP and 3-PBA increased rapidly after ingestion, with average peak values at 3.1 and 4.0h post-dosing, respectively; subsequent elimination phase showed a rapid decay with a mean half-life (t ½ ) of ≈5.3 and 6.4h for CFMP and 3-PBA, respectively. Urinary rate time courses displayed a profile similar to the plasma concentration-time curves with corresponding mean t ½ of ≈4.2 and 5.9h. In the 84-h period post-treatment, on average 21% of lambda-cyhalothrin dose were excreted in urine as CFMP as compared to 30% as 3-PBA. Overall, CFMP and 3-PBA metabolites were confirmed to be major metabolites of lambda-cyhalothrin and exhibited similar kinetics with short half-lives; they thus both appear as useful biomarkers of exposure to lambda-cyhalothrin in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Urinary Phenylacetylglutamine as Dosing Biomarker for Patients with Urea Cycle Disorders

PubMed Central

Mokhtarani, M; Diaz, GA; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, SA; Gallagher, R; Bartholomew, D; Harding, CO; Korson, MS; McCandless, SE; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, JL; Sreenath-Nagamani, Sandesh; Summar, M; LeMons, C; Dickinson, K; Coakley, DF; Moors, TL; Lee, B; Scharschmidt, BF

2013-01-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). Study Design These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6–17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Results Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5–31.8 g/day and of sodium phenylbutyrate ranging from 1.3–31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% –5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% -to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r=0.730, p<0.001) or as total 24-hour excretion (r=0.791 p<0.001), followed by plasma phenylacetylglutamine AUC24-hour, plasma phenylacetic acid AUC24-hour and phenylbutyric acid AUC24-hour. Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. Conclusion The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. PMID:22958974

Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders.

PubMed

Mokhtarani, M; Diaz, G A; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, S A; Gallagher, R; Bartholomew, D; Harding, C O; Korson, M S; McCandless, S E; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, J L; Sreenath-Nagamani, Sandesh; Summar, M; Lemons, C; Dickinson, K; Coakley, D F; Moors, T L; Lee, B; Scharschmidt, B F

2012-11-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r = 0.730, p < 0.001) or as total 24-hour excretion (r = 0.791 p<0.001), followed by plasma phenylacetylglutamine AUC(24-hour), plasma phenylacetic acid AUC(24-hour) and phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of sodium intake and diet on racial differences in urinary potassium excretion: results from the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial.

PubMed

Turban, Sharon; Thompson, Carol B; Parekh, Rulan S; Appel, Lawrence J

2013-01-01

We previously showed that African Americans excreted less urinary potassium than whites, even while consuming similar diets in the Dietary Approaches to Stop Hypertension (DASH) trial. We hypothesized that a low-sodium diet may eliminate these differences. Data from the DASH-Sodium randomized controlled feeding trial were analyzed. 412 adults with prehypertension or stage 1 hypertension. Random assignment to either a typical American "control" diet (1.7 g [43 mEq] potassium/2,100 kcal/d) or the DASH diet (4.1 g [105 mEq] potassium/2,100 kcal/d). Within each diet, participants received 3 levels of sodium intake in random order for 30 days. 24-hour urine samples were analyzed at the end of each period. The primary outcome was urinary potassium excretion. On the DASH diet, African Americans consistently excreted significantly less urinary potassium (mean 24-hour urinary potassium excretion, 2,594 ± 961 mg [66 ± 25 mEq]) than whites (3,412 ± 1,016 mg [87 ± 26 mEq]) at the highest sodium level; adjusted (P < 0.001); this difference was not altered by sodium level (P = 0.6 comparing white to African American difference in urinary potassium excretion on high- vs low-sodium diet). In contrast, there was a smaller but significant white-African American difference in mean daily urinary potassium excretion in participants fed the control/high-sodium diet that was not present in the control/low-sodium diet (adjusted differences of 281 mg [7 mEq]/d vs 20 mg [0.5 mEq]/d, respectively; P = 0.007). Significant interactions were found between race and diet (P < 0.001) and between race and sodium (P = 0.02). Single rather than multiple urine collections were available at each time. Lack of stool potassium and sweat potassium values. Racial differences in urinary potassium excretion depend on sodium intake and diet. Our results may help explain the previously documented large variability in urinary potassium excretion. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Spectrofluorimetric determination of 3-methylflavone-8-carboxylic acid, the main active metabolite of flavoxate hydrochloride in human urine.

PubMed

Zaazaa, Hala E; Mohamed, Afaf O; Hawwam, Maha A; Abdelkawy, Mohamed

2015-01-05

A simple, sensitive and selective spectrofluorimetric method has been developed for the determination of 3-methylflavone-8-carboxylic acid as the main active metabolite of flavoxate hydrochloride in human urine. The proposed method was based on the measurement of the native fluorescence of the metabolite in methanol at an emission wavelength 390 nm, upon excitation at 338 nm. Moreover, the urinary excretion pattern has been calculated using the proposed method. Taking the advantage that 3-methylflavone-8-carboxylic acid is also the alkaline degradate, the proposed method was applied to in vitro determination of flavoxate hydrochloride in tablets dosage form via the measurement of its corresponding degradate. The method was validated in accordance with the ICH requirements and statistically compared to the official method with no significant difference in performance. Copyright © 2014 Elsevier B.V. All rights reserved.

A metabolomics-driven approach to predict cocoa product consumption by designing a multimetabolite biomarker model in free-living subjects from the PREDIMED study.

PubMed

Garcia-Aloy, Mar; Llorach, Rafael; Urpi-Sarda, Mireia; Jáuregui, Olga; Corella, Dolores; Ruiz-Canela, Miguel; Salas-Salvadó, Jordi; Fitó, Montserrat; Ros, Emilio; Estruch, Ramon; Andres-Lacueva, Cristina

2015-02-01

The aim of the current study was to apply an untargeted metabolomics strategy to characterize a model of cocoa intake biomarkers in a free-living population. An untargeted HPLC-q-ToF-MS based metabolomics approach was applied to human urine from 32 consumers of cocoa or derived products (CC) and 32 matched control subjects with no consumption of cocoa products (NC). The multivariate statistical analysis (OSC-PLS-DA) showed clear differences between CC and NC groups. The discriminant biomarkers identified were mainly related to the metabolic pathways of theobromine and polyphenols, as well as to cocoa processing. Consumption of cocoa products was also associated with reduced urinary excretions of methylglutarylcarnitine, which could be related to effects of cocoa exposure on insulin resistance. To improve the prediction of cocoa consumption, a combined urinary metabolite model was constructed. ROC curves were performed to evaluate the model and individual metabolites. The AUC values (95% CI) for the model were 95.7% (89.8-100%) and 92.6% (81.9-100%) in training and validation sets, respectively, whereas the AUCs for individual metabolites were <90%. The metabolic signature of cocoa consumption in free-living subjects reveals that combining different metabolites as biomarker models improves prediction of dietary exposure to cocoa. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Urinary Sodium and Potassium Excretion and Dietary Sources of Sodium in Maputo, Mozambique.

PubMed

Queiroz, Ana; Damasceno, Albertino; Jessen, Neusa; Novela, Célia; Moreira, Pedro; Lunet, Nuno; Padrão, Patrícia

2017-08-03

This study aimed to evaluate the urinary excretion of sodium and potassium, and to estimate the main food sources of sodium in Maputo dwellers. A cross-sectional evaluation of a sample of 100 hospital workers was conducted between October 2012 and May 2013. Sodium and potassium urinary excretion was assessed in a 24-h urine sample; creatinine excretion was used to exclude unlikely urine values. Food intake in the same period of urine collection was assessed using a 24-h dietary recall. The Food Processor Plus ® was used to estimate sodium intake corresponding to naturally occurring sodium and sodium added to processed foods (non-discretionary sodium). Salt added during culinary preparations (discretionary sodium) was computed as the difference between urinary sodium excretion and non-discretionary sodium. The mean (standard deviation) urinary sodium excretion was 4220 (1830) mg/day, and 92% of the participants were above the World Health Organization (WHO) recommendations. Discretionary sodium contributed 60.1% of total dietary sodium intake, followed by sodium from processed foods (29.0%) and naturally occurring sodium (10.9%). The mean (standard deviation) urinary potassium excretion was 1909 (778) mg/day, and 96% of the participants were below the WHO potassium intake recommendation. The mean (standard deviation) sodium to potassium molar ratio was 4.2 (2.4). Interventions to decrease sodium and increase potassium intake are needed in Mozambique.

Urinary Sodium and Potassium Excretion and Dietary Sources of Sodium in Maputo, Mozambique

PubMed Central

Queiroz, Ana; Damasceno, Albertino; Jessen, Neusa; Novela, Célia; Moreira, Pedro; Lunet, Nuno

2017-01-01

This study aimed to evaluate the urinary excretion of sodium and potassium, and to estimate the main food sources of sodium in Maputo dwellers. A cross-sectional evaluation of a sample of 100 hospital workers was conducted between October 2012 and May 2013. Sodium and potassium urinary excretion was assessed in a 24-h urine sample; creatinine excretion was used to exclude unlikely urine values. Food intake in the same period of urine collection was assessed using a 24-h dietary recall. The Food Processor Plus® was used to estimate sodium intake corresponding to naturally occurring sodium and sodium added to processed foods (non-discretionary sodium). Salt added during culinary preparations (discretionary sodium) was computed as the difference between urinary sodium excretion and non-discretionary sodium. The mean (standard deviation) urinary sodium excretion was 4220 (1830) mg/day, and 92% of the participants were above the World Health Organization (WHO) recommendations. Discretionary sodium contributed 60.1% of total dietary sodium intake, followed by sodium from processed foods (29.0%) and naturally occurring sodium (10.9%). The mean (standard deviation) urinary potassium excretion was 1909 (778) mg/day, and 96% of the participants were below the WHO potassium intake recommendation. The mean (standard deviation) sodium to potassium molar ratio was 4.2 (2.4). Interventions to decrease sodium and increase potassium intake are needed in Mozambique. PMID:28771193

Urinary protein-to-creatinine ratio versus 24-h proteinuria in the screening for nephropathy in HIV patients.

PubMed

Antonello, Vicente Sperb; Poli-De-Figueiredo, Carlos Eduardo; Antonello, Ivan Carlos Ferreira; Tovo, Cristiane Valle

2015-06-01

To determine the correlation between protein-to-creatinine ratio and 24-h urinary protein, proteinuria was measured in 45 patients attending a public HIV clinic in Porto Alegre, Brazil, using 24-h urinary protein excretion (24hUP) and urinary protein-to-creatinine ratio. Spearman's correlation test was done to evaluate the association between spot protein-to-creatinine ratio and 24hUP. The limits of agreement between the two methods were analysed by the Bland-Altman method. For protein excretion <1 g/day, limits (95%) of agreement of protein-to-creatinine ratio and 24hUP were +0.112 and -0.097 g/day. A strong correlation (r = 0.957) was found between protein-to-creatinine ratio and 24hUP excretion. The conclusion is that the protein-to-creatinine ratio in spot urine specimens is an accurate, convenient and reliable screening method to estimate the urinary protein excretion in HIV patients to detect abnormal urinary protein loss. Further studies are required to evaluate renal disease in HIV patients with chronic renal disease and higher urinary protein excretion. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Sodium-bicarbonated mineral water decreases aldosterone levels without affecting urinary excretion of bone minerals.

PubMed

Schoppen, Stefanie; Pérez-Granados, Ana M; Carbajal, Angeles; Sarriá, Beatriz; Navas-Carretero, Santiago; Pilar Vaquero, M

2008-06-01

AIM To assess in healthy postmenopausal women the influence of consuming sodium-bicarbonated mineral water on postprandial evolution of serum aldosterone and urinary electrolyte excretion. Eighteen postmenopausal women consumed 500 ml of two sodium-bicarbonated mineral waters (sodium-bicarbonated mineral water 1 and sodium-bicarbonated mineral water 2) and a low-mineral water with a standard meal. Postprandial blood samples were taken at 60, 120, 240, 360 and 420 min and aldosterone concentrations were measured. Postprandial urinary minerals were determined. Urinary and total mineral excretion and urinary mineral concentrations did not differ except for sodium concentration, which was significantly higher with sodium-bicarbonated mineral water 1 than with low-mineral water (P = 0.005). There was a time effect (P = 0.003) on the aldosterone concentration. At 120 min, aldosterone concentrations were lower with sodium-bicarbonated mineral water 1 (P = 0.021) and sodium-bicarbonated mineral water 2 (P = 0.030) compared with low-mineral water. Drinking a sodium-rich bicarbonated mineral water with a meal increases urinary sodium concentration excretion without changes in the excretion of potassium and bone minerals.

N-Acetyl-4-aminophenol (paracetamol), N-acetyl-2-aminophenol and acetanilide in urine samples from the general population, individuals exposed to aniline and paracetamol users.

PubMed

Dierkes, Georg; Weiss, Tobias; Modick, Hendrik; Käfferlein, Heiko Udo; Brüning, Thomas; Koch, Holger M

2014-01-01

Epidemiological studies suggest associations between the use of N-acetyl-4-aminophenol (paracetamol) during pregnancy and increased risks of reproductive disorders in the male offspring. Previously we have reported a ubiquitous urinary excretion of N-acetyl-4-aminophenol in the general population. Possible sources are (1) direct intake of paracetamol through medication, (2) paracetamol residues in the food chain and (3) environmental exposure to aniline or related substances that are metabolized into N-acetyl-4-aminophenol. In order to elucidate the origins of the excretion of N-acetyl-4-aminophenol in urine and to contribute to the understanding of paracetamol and aniline metabolism in humans we developed a rapid, turbulent-flow HPLC-MS/MS method with isotope dilution for the simultaneous quantification of N-acetyl-4-aminophenol and two other aniline related metabolites, N-acetyl-2-aminophenol and acetanilide. We applied this method to three sets of urine samples: (1) individuals with no known exposure to aniline and also no recent paracetamol medication; (2) individuals after occupational exposure to aniline but no paracetamol medication and (3) paracetamol users. We confirmed the omnipresent excretion of N-acetyl-4-aminophenol. Additionally we revealed an omnipresent excretion of N-acetyl-2-aminophenol. In contrast, acetanilide was only found after occupational exposure to aniline, not in the general population or after paracetamol use. The results lead to four preliminary conclusions: (1) other sources than aniline seem to be responsible for the major part of urinary N-acetyl-4-aminophenol in the general population; (2) acetanilide is a metabolite of aniline in man and a valuable biomarker for aniline in occupational settings; (3) aniline baseline levels in the general population measured after chemical hydrolysis do not seem to originate from acetanilide and hence not from a direct exposure to aniline itself and (4) N-acetyl-2-aminophenol does not seem to be related to aniline nor to N-acetyl-4-aminophenol in man. Copyright © 2013 Elsevier GmbH. All rights reserved.

Human urinary metabolic patterns of the designer benzodiazepines flubromazolam and pyrazolam studied by liquid chromatography-high resolution mass spectrometry.

PubMed

Pettersson Bergstrand, Madeleine; Meyer, Markus R; Beck, Olof; Helander, Anders

2018-03-01

Over the past ~8 years, hundreds of unregulated new psychoactive substances (NPS) of various chemical categories have been introduced as recreational drugs through mainly open online trade. This study was performed to further investigate the human metabolic pattern of the NPS, or designer benzodiazepines flubromazolam and pyrazolam, and to propose analytical targets for urine drug testing of these substances. The urine samples originated from patient samples confirmed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) analysis to contain flubromazolam or pyrazolam. The LC-HRMS/MS system consisted of a YMC-UltraHT Hydrosphere C18 column (YMC, Dinslaken, Germany) coupled to a Thermo Scientific (Waltham, MA, USA) Q Exactive Orbitrap MS operating in positive electrospray mode. The samples were analyzed both with and without enzymatic hydrolysis using β-glucuronidase. Besides the parent compounds, the main urinary excretion products were parent glucuronides, mono-hydroxy metabolites, and mono-hydroxy glucuronides. In samples prepared without hydrolysis, the most common flubromazolam metabolites were 1 of the mono-hydroxy glucuronides and 1 of the parent glucuronides. For pyrazolam, a parent glucuronide was the most common metabolite. These 3 metabolites were detected in all samples and were considered the primary targets for urine drug testing and confirmation of intake. After enzymatic hydrolysis of the urine samples, a 2-19-fold increase in the concentration of flubromazolam was found, highlighting the value of hydrolysis for this analyte. With hydrolysis, the flubromazolam hydroxy metabolites should be used as target metabolites. Copyright © 2017 John Wiley & Sons, Ltd.

Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

PubMed Central

Tynkevich, Elena; Flamant, Martin; Haymann, Jean-Philippe; Metzger, Marie; Thervet, Eric; Boffa, Jean-Jacques; Vrtovsnik, François; Houillier, Pascal; Froissart, Marc; Stengel, Bénédicte

2014-01-01

Background Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to <15 mL/min/1.73 m2, and from 9.6±1.9 to 7.6±2.5 (0.16±0.03 to 0.12±0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m2 per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass. PMID:25401694

Quantitative analysis of urinary glycine conjugates by high performance liquid chromatography: excretion of hippuric acid and methylhippuric acids in the urine of subjects exposed to vapours of toluene and xylenes.

PubMed

Ogata, M; Taguchi, T

1986-01-01

A new method for the direct determination of hippuric acid (HA) and o-, m- and p-methylhippuric acids (MHAs) in the urine, metabolites of toluene and o-, m- and p-xylenes by high performance liquid chromatography (HPLC) is described. A stainless-steel column packed with silica gel having dinitrophenyl residue and a mixed solution of methanol/water/acetic acid (80/20/0.2) containing tetra-n-butylammonium bromide (0.2% w/v) as mobile phase was used. Concentrations of HA and MHAs were estimated from their peak height at a wave length of 225 nm. Urine can be analyzed directly without solvent extraction or pretreatment to obtain complete separation of HA and o-, m- and p-MHAs. Urine samples from male workers exposed to toluene or xylenes were analyzed for HA or MHAs. The urinary levels of HA and MHAs increased by exposure to toluene and xylenes in proportion to the environmental concentrations of the solvents, although there is a considerable variation in metabolite concentrations. The slope of regression line between toluene and HA and that between m-xylene and m-MHA were similar. The urinary concentrations of HA and MHAs corresponding to 100 ppm (TLV) of toluene was 2.35 g/g creatinine and that of m-MHA corresponding to 100 ppm (TLV) of m-xylene was 2.05 g/g creatinine. The warning levels of the urinary metabolite concentrations of a group of workers and that of an individual worker corresponding to TLV of organic solvent concentration is discussed.

Intake and urinary excretion of sodium chloride under varying conditions of effort and environment heat

NASA Technical Reports Server (NTRS)

Zohar, E.; Adar, R.; Tennenbaum, J.; Kesten, M.

1982-01-01

Intake and urinary excretion of sodium were investigated in a group of young, healthy and acclimated men. The sodium excretions of workers and of machinists in the engine rooms of a ship were also investigated.

Calciuric effects of short-term dietary loading of protein, sodium chloride and potassium citrate in prepubescent girls.

PubMed

Duff, T L; Whiting, S J

1998-04-01

Studies using adult human subjects indicate that dietary protein and sodium chloride have negative effects on the retention of calcium by increasing urinary calcium excretion, while alkaline potassium improves calcium retention along with decreasing urinary calcium losses. This study investigated the effect of these dietary factors on acute urinary calcium excretion in 14 prepubescent girls age 6.7 to 10.0 years. Subjects provided a fasting urine sample then consumed a meal containing one of five treatments: moderate protein (MP) providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na), high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and unless intentionally altered, components of interest except phosphate were equal between treatments. Each subject completed all five treatments. Urinary calcium excretion rose after the meal, peaking at 1.5 hours. There were no significant differences in calcium excretion between treatments at any time point. The high protein treatments did not result in a significant increase in either net acid or sulfate excretion at 1.5 hours compared to moderate protein. Dietary sodium chloride had no effect on urinary sodium or calcium excretion over the 3 hours. After the potassium treatment, sodium excretion increased (p< or =0.002) and net acid excretion decreased (p<0.001) compared to other treatments at 1.5 hours. In children, a simultaneous increase in protein and phosphorus due to increased milk protein intake did not increase acute urinary calcium excretion. An effect of dietary sodium chloride on acute urinary calcium excretion was not observed. Both these findings were similar to those of adult studies previously conducted in the same laboratory using similar format and treatments. Potassium citrate was not hypocalciuric in children, a response differing from that for adults, who have shown a decrease in acute urinary calcium excretion in response to alkaline potassium treatment. Further characterization of calciuric responses to dietary factors is required for children, who may differ from adults in many respects.

Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia.

PubMed

Halhali, Ali; Díaz, Lorenza; Avila, Euclides; Ariza, Ana Carolina; Garabédian, Michèle; Larrea, Fernando

2007-03-01

During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.

Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations.

PubMed

Blázquez-Medela, Ana M; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M; Romero, Miguel; Duarte, Juan M; López-Hernández, Francisco J; López-Novoa, José M; Martínez-Salgado, Carlos

2015-10-01

Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys.We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage.Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments.The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening.KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage.

Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass.

PubMed

Park, S M; Joung, J Y; Cho, Y Y; Sohn, S Y; Hur, K Y; Kim, J H; Kim, S W; Chung, J H; Lee, M K; Min, Y-K

2015-03-01

High salt intake is a well-recognized risk factor of osteoporosis for its modulating effect on calcium metabolism. To understand the effect of dietary sodium on bone turnover, we evaluated the association between urinary sodium excretion and bone turnover markers in Korean postmenopausal women with low bone mass. A retrospective review of medical records at a single institution identified 537 postmenopausal women who were first diagnosed with osteopenia or osteoporosis between 2008 and 2013. Subjects were stratified by low (<2 g/day, n=77), moderate (2-4.4 g/day, n=354) and high (⩾4.4 g/day, n=106) sodium excretion. A 24-h urine was collected to estimate sodium, calcium and creatinine. Bone turnover markers and calciotropic hormones were measured in serum. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Sodium intake was positively associated with urinary sodium excretion (P=0.006, r=0.29). Bone turnover markers were significantly higher in the moderate-to-high urinary sodium excretion group (⩾2 g/day) than in the low urinary sodium excretion group (<2 g/day); CTX-I (C-telopeptides of type I collagen) was 21.3% higher (P=0.001) and osteocalcin (OC) was 15.7% higher (P=0.004). Calciotropic hormones and BMD were not significantly different across the sodium excretion groups. High urinary sodium excretion (⩾2 g/day) increased bone turnover markers in Korean postmenopausal women, suggesting that excessive sodium intake might accelerate bone turnover.

Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100.

PubMed

Yu, Rosie Z; Kim, Tae-Won; Hong, An; Watanabe, Tanya A; Gaus, Hans J; Geary, Richard S

2007-03-01

The pharmacokinetics of a 2'-O-(2-methoxyethyl)-modified oligonucleotide, ISIS 301012 [targeting human apolipoprotein B-100 (apoB-100)], was characterized in mouse, rat, monkey, and human. Plasma pharmacokinetics following parental administration was similar across species, exhibiting a rapid distribution phase with t(1/2alpha) of several hours and a prolonged elimination phase with t(1/2beta) of days. The prolonged elimination phase represents equilibrium between tissues and circulating drug due to slow elimination from tissues. Absorption was nearly complete following s.c. injection, with bioavailability ranging from 80 to 100% in monkeys. Plasma clearance scaled well across species as a function of body weight alone, and this correlation was improved when corrected for plasma protein binding. In all of the animal models studied, the highest tissue concentrations of ISIS 301012 were observed in kidney and liver. Urinary excretion was less than 3% in monkeys and human in the first 24 h. ISIS 301012 is highly bound to plasma proteins, probably preventing rapid removal by renal filtration. However, following 25 mg/kg s.c. administration in mouse and 5-mg/kg i.v. bolus administration in rat, plasma concentrations of ISIS 301012 exceeded their respective protein binding capacity. Thus, urinary excretion increased to 16% or greater within the first 24 h. Albeit slow, urinary excretion of ISIS 301012 and its shortened metabolites is the ultimate elimination pathway of this compound, as demonstrated by 32% of dose recovered in total excreta by 14 days in a rat mass balance study. The pharmacokinetics of ISIS 301012 in human is predictable from the pharmacokinetics measured in animals. The pharmacokinetic properties of ISIS 301012 provide guidance for clinical development and support infrequent dose administration.

The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration.

PubMed Central

Barber, H E; Bourne, G R; Calvey, T N; Muir, K T

1975-01-01

1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug. PMID:173444

Pharmacokinetics, excretion of 8-cetylberberine and its main metabolites in rat urine.

PubMed

Hu, Yuli; Fan, Shoujun; Liao, Xiaobing; Chen, Chao; Su, Liang; Li, Xuegang

2017-01-05

Berberine (BBR) is a bioactive plant ingredient derived from the roots and bark of Berberis aristata and Coptis chinensis and has a wide variety of pharmacological effects. 8-cetylberberine (8-BBR-C16) is the berberine (BBR) derivative reconstructed from adding octadecyl at C-8 of BBR to enhance its activity. This study presents a reliable method for the determination of BBR and 8-BBR-C16 in rat plasma, urine and feces. BBR and 8-BBR-C16 were determined by HPLC-UV after liquid-liquid extraction for plasma samples, and solid-phase extraction for urinary and fecal samples. The method was linear over the concentration range of 10-300 ng·ml -1 for the plasma samples, 25-2000 ng·ml -1 for the urinary samples, and 100-2000 ng·g -1 for the fecal samples. Furthermore, a metabolic investigation on urine was performed by LC/MS/MS analysis to identify the structures of 8-BBR-C16 metabolites by full scan and product ion scan. Adult Sprague-Dawley rats were divided into two groups. In the control group, rats received 80 mg·kg -1 BBR, and in the drug-treated group, rats received 80 mg·kg -1 8-BBR-C16. The results indicate that there were significant differences in the pharmacokinetic parameters and in the accumulated excretion levels between the control group and the drug-treated group. The C max and AUC 0-t of 8-BBR-C16 were 2.8 and 12.9 times higher than those of BBR, and the relative bioavailability of BBR to 8-BBR-C16 was 7.7%. The total excretion amount through the urine and feces of 8-BBR-C16 was 76.9%, but that of BBR was only 20.5%. Additionally, 8-BBR-C16 was metabolized in rat urine with phase I demethylation and phase II glucuronidation or sulfation. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolism and disposition of oral dabrafenib in cancer patients: proposed participation of aryl nitrogen in carbon-carbon bond cleavage via decarboxylation following enzymatic oxidation.

PubMed

Bershas, David A; Ouellet, Daniele; Mamaril-Fishman, Donna B; Nebot, Noelia; Carson, Stanley W; Blackman, Samuel C; Morrison, Royce A; Adams, Jerry L; Jurusik, Kristen E; Knecht, Dana M; Gorycki, Peter D; Richards-Peterson, Lauren E

2013-12-01

A phase I study was conducted to assess the metabolism and excretion of [(14)C]dabrafenib (GSK2118436; N-{3-[5-(2-amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzene sulfonamide, methanesulfonate salt), a BRAF inhibitor, in four patients with BRAF V600 mutation-positive tumors after a single oral dose of 95 mg (80 µCi). Assessments included the following: 1) plasma concentrations of dabrafenib and metabolites using validated ultra-high-performance liquid chromatography--tandem mass spectrometry methods, 2) plasma and blood radioactivity, 3) urinary and fecal radioactivity, and 4) metabolite profiling. Results showed the mean total recovery of radioactivity was 93.8%, with the majority recovered in feces (71.1% of administered dose). Urinary excretion accounted for 22.7% of the dose, with no detection of parent drug in urine. Dabrafenib is metabolized primarily via oxidation of the t-butyl group to form hydroxy-dabrafenib. Hydroxy-dabrafenib undergoes further oxidation to carboxy-dabrafenib, which subsequently converts to desmethyl-dabrafenib via a pH-dependent decarboxylation. The half-lives for carboxy- and desmethyl-dabrafenib were longer than for parent and hydroxy-dabrafenib (18-20 vs. 5-6 hours). Based on area under the plasma concentration-time curve, dabrafenib, hydroxy-, carboxy-, and desmethyl-dabrafenib accounted for 11%, 8%, 54%, and 3% of the plasma radioactivity, respectively. These results demonstrate that the major route of elimination of dabrafenib is via oxidative metabolism (48% of the dose) and biliary excretion. Based on our understanding of the decarboxylation of carboxy-dabrafenib, a low pH-driven, nonenzymatic mechanism involving participation of the aryl nitrogen is proposed to allow prediction of metabolic oxidation and decarboxylation of drugs containing an aryl nitrogen positioned α to an alkyl (ethyl or t-butyl) side chain.

Urinary Excretion of N-Nitroso Compounds in Rats Fed Sodium Nitrite and/or Hot Dogs

PubMed Central

2015-01-01

Nitrite-treated meat is a reported risk factor for colon cancer. Mice that ingested sodium nitrite (NaNO2) or hot dogs (a nitrite-treated product) showed increased fecal excretion of apparent N-nitroso compounds (ANC). Here, we investigated for the first time whether rats excrete increased amounts of ANC in their urine after they are fed NaNO2 and/or hot dogs. Rats were treated for 7 days with NaNO2 in drinking water or were fed hot dogs. Their 24 h urine samples were analyzed for ANC by thermal energy analysis on days 1–4 after nitrite or hot dog treatment was stopped. For two rats fed 480 mg NaNO2/L drinking water, mean urinary ANC excretion on days 1–4 was 30, 5.2, 2.5, and 0.8 nmol/day, respectively. For two to eight rats/dose given varied NaNO2 doses, mean urinary ANC output on day 1 increased from 0.9 (for no nitrite) to 37 (for 1000 mg NaNO2/L drinking water) nmol ANC/day. Urine samples of four rats fed 40–60% hot dogs contained 12–13 nmol ANC on day 1. Linear regression analysis showed highly significant correlations between urinary ANC excretion on day 1 after stopping treatment and varied (a) NaNO2 level in drinking water for rats fed semipurified or commercials diet and (b) hot dog levels in the diet. Some correlations remained significant up to 4 days after nitrite treatment was stopped. Urinary output of ANC precursors (compounds that yield ANC after mild nitrosation) for rats fed semipurified or commercial diet was 11–17 or 23–48 μmol/day, respectively. Nitrosothiols and iron nitrosyls were not detected in urinary ANC and ANCP. Excretion of urinary ANC was about 60% of fecal ANC excretion for 1 to 2 days after NaNO2 was fed. Administered NaNO2 was not excreted unchanged in rat urine. We conclude that urinary ANC excretion in humans could usefully be surveyed to indicate exposure to N-nitroso compounds. PMID:25183213

Renal outcomes and dietary potassium: the overshadowed electrolyte?

PubMed

Jablonski, Kristen L; Kendrick, Jessica B

2014-12-01

Smyth et al. examined the association between urinary sodium and potassium excretion and adverse renal outcomes in adults at high cardiovascular risk. They found no association between urinary sodium excretion and adverse renal outcomes, but a reduced odds of adverse renal outcomes with higher urinary potassium excretion. It will be important to ascertain whether this finding holds true in individuals free from vascular disease and diabetes, as well as in patients with chronic kidney disease.

Relation of Urinary Calcium and Magnesium Excretion to Blood Pressure

PubMed Central

Kesteloot†, Hugo; Tzoulaki, Ioanna; Brown, Ian J.; Chan, Queenie; Wijeyesekera, Anisha; Ueshima, Hirotsugu; Zhao, Liancheng; Dyer, Alan R.; Unwin, Robert J.; Stamler, Jeremiah; Elliott, Paul

2011-01-01

Data indicate an inverse association between dietary calcium and magnesium intakes and blood pressure (BP); however, much less is known about associations between urinary calcium and magnesium excretion and BP in general populations. The authors assessed the relation of BP to 24-hour excretion of calcium and magnesium in 2 cross-sectional studies. The International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP) comprised 4,679 persons aged 40–59 years from 17 population samples in China, Japan, the United Kingdom, and the United States, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) comprised 10,067 persons aged 20–59 years from 52 samples around the world. Timed 24-hour urine collections, BP measurements, and nutrient data from four 24-hour dietary recalls (INTERMAP) were collected. In multiple linear regression analyses, urinary calcium excretion was directly associated with BP. After adjustment for multiple confounders (including weight, height, alcohol intake, calcium intake, urinary sodium level, and urinary potassium intake), systolic BP was 1.9 mm Hg higher per each 4.1 mmol per 24 hours (2 standard deviations) of higher urinary calcium excretion (associations were smaller for diastolic BP) in INTERMAP. Qualitatively similar associations were observed in INTERSALT analyses. Associations between magnesium excretion and BP were small and nonsignificant for most of the models examined. The present data suggest that altered calcium homoeostasis, as exhibited by increased calcium excretion, is associated with higher BP levels. PMID:21624957

Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

PubMed

Sato, Emiko; Wang, An Yi; Satoh, Michihiro; Nishikiori, Yoko; Oba-Yabana, Ikuko; Yoshida, Mai; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru; Mori, Takefumi

2018-05-07

Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

Role of vasopressin in regulation of renal kinin excretion in Long-Evans and diabetes insipidus rats.

PubMed Central

Kauker, M L; Crofton, J T; Share, L; Nasjletti, A

1984-01-01

To study the relationship between vasopressin and the renal kallikrein-kinin system we measured the rate of excretion of kinins into the urine of anesthetized rats during conditions of increased and decreased vasopressin level. The excretion of immunoreactive kinins in Brattleboro rats with hereditary diabetes insipidus (DI) (24 +/- 3 pg min-1 kg-1) was lower than in the control Long Evans (LE) rats (182 +/- 22 pg min-1 kg-1; P less than 0.05). The DI rats also exhibited negligible urinary excretion of immunoreactive vasopressin, reduced urine osmolality, and increased urine flow and kininogenase excretion. In LE rats, volume expansion by infusion of 0.45% NaCl-2.5% dextrose to lower vasopressin secretion reduced (P less than 0.05) kinin excretion, vasopressin excretion, and urine osmolality to 41, 26, and 15% of their respective control values, while increasing (P less than 0.05) urine flow and kininogenase excretion. On the other hand, the infusion of 5% NaCl, which promotes vasopressin secretion, increased (P less than 0.05) the urinary excretion of kinins and vasopressin to 165 and 396% of control, while increasing (P less than 0.05) urine flow and kininogenase excretion. Infusion of vasopressin (1.2 mU/h, intravenous) enhanced (P less than 0.05) kinin excretion by two to threefold in DI rats and in LE rats during volume expansion with 0.45% NaCl-2.5% dextrose, while decreasing urine flow and increasing urine osmolality. This study demonstrates that the urinary excretion of immunoreactive kinins varies in relation to the urinary level of vasopressin, irrespective of urine volume and osmolality and of the urinary excretions of sodium and kininogenase. The study suggests a role for vasopressin in promoting the activity of the renal kallikrein-kinin system in the rat. PMID:6561201

Urinary nandrolone metabolite detection after ingestion of a nandrolone precursor.

PubMed

Watson, Phillip; Judkins, Catherine; Houghton, Ed; Russell, Caroline; Maughan, Ronald J

2009-04-01

Quantities of various anabolic/androgenic steroids have been found in dietary supplements without their presence being disclosed on the label. The aim of this study was to quantify the excretion patterns of the diagnostic metabolites, 19-norandrosterone (19-NA), and 19-noretiocholanolone (19-NE) after ingestion of small doses of 19-nor-4-androstene-3,17-dione (19-norandrostenedione). Eleven males and nine females entered the laboratory in the morning after an overnight fast. An initial urine sample was collected, and volunteers then ingested 500 mL of water containing 5 g of creatine monohydrate and 1.0, 2.5, or 5.0 microg of 19-norandrostenedione. The volume of each urine void was measured, and an aliquot was taken. Samples were analyzed for the metabolites 19-NA and 19-NE by GCMS. Baseline urinary 19-NA concentrations were 0.19 +/- 0.14 ng x mL. Ingestion of the supplement resulted in peak mean urinary 19-NA concentrations of 0.68 +/- 0.36, 1.56 +/- 0.86, and 3.89 +/- 3.11 ng.mL in the 1.0-, 2.5-, or 5.0-microg trials, respectively. Under current WADA regulations, ingestion of the 1.0-microg dose produced 0 positive doping tests, 5 subjects (20%) tested positive in the 2.5-microg trial, and 15 subjects (75%) had urinary 19-NA concentrations exceeding 2 ng x mL after ingesting creatine containing 5.0 microg of the steroid. The recovery of the ingested dose was highly variable between individuals, with values ranging from 11% to 84% (mean +/- SD = 47% +/- 18%). Ingestion of trace amounts of 19-norandrostenedione can result in transient elevations of urinary 19-NA and 19-NE concentrations. The addition of as little as 2.5 microg of 19-norandrostenedione to a supplement (0.00005% contamination) appears sufficient to result in a doping violation in some individuals.

Renal Function, Bisphenol A, and Alkylphenols: Results from the National Health and Nutrition Examination Survey (NHANES 2003–2006)

PubMed Central

You, Li; Zhu, Xiangzhu; Shrubsole, Martha J.; Fan, Hong; Chen, Jing; Dong, Jie; Hao, Chuan-Ming; Dai, Qi

2011-01-01

Background Urinary excretion of bisphenol A (BPA) and alkylphenols (APs) was used as a biomarker in most previous studies, but no study has investigated whether urinary excretion of these environmental phenols differed by renal function. Objective We estimated the association between renal function and urinary excretion of BPA and APs. Methods Analyses were conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2006. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) Study equation and by the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Regression models were used to calculate geometric means of urinary BPA and APs excretion by eGFR category (≥ 90, 60–90, < 60 mL/min/m2) after adjusting for potential confounding factors. Results When we used the MDRD Study equation, participants without known renal disease (n = 2,573), 58.2% (n = 1,499) had mildly decreased renal function or undiagnosed chronic kidney disease. The adjusted geometric means for urinary BPA excretion decreased with decreasing levels of eGFR (p for trend = 0.04). The associations appeared primarily in females (p for trend = 0.03). Urinary triclosan excretion decreased with decreasing levels of eGFR (p for trend < 0.01) for both males and females, and the association primarily appeared in participants < 65 years of age. The association between BPA and eGFR was nonsignificant when we used the CKD-EPI equation. Conclusions Urinary excretion of triclosan, and possibly BPA, decreased with decreasing renal function. The associations might differ by age or sex. Further studies are necessary to replicate our results and understand the mechanism. PMID:21147601

Iodine Excretion in 24-hour Urine Collection and Its Dietary Determinants in Healthy Japanese Adults

PubMed Central

Katagiri, Ryoko; Asakura, Keiko; Uechi, Ken; Masayasu, Shizuko; Sasaki, Satoshi

2016-01-01

Background Since seaweed is a common component of the Japanese diet, iodine intake in Japanese is expected to be high. However, urinary iodine excretion, measured using 24-hour urine samples, and its dietary determinants are not known. Methods Apparently healthy adults aged 20 to 69 years living in 20 areas throughout Japan were recruited in February and March, 2013. Urinary iodine excretion was evaluated using 24-hour urine collected from 713 subjects (362 men and 351 women), and the difference among age groups was assessed. The association between dietary intake of food groups and urinary iodine excretion was assessed among 358 subjects who completed a semi-weighed 4-day diet record (DR) and urine collection. The correlations between iodine intake and iodine excretion were also evaluated, and correlation coefficients were calculated for iodine intake in the DR of the overlapping day or the DR 1 day before and after urine collection. Results Median iodine excretion in 24-hour urine was 365 µg, and excretion was significantly higher in older subjects. Iodine intake estimated by the DRs was significantly correlated with urinary iodine excretion when DRs and urine collection were obtained on the same day (r = 0.37). After adjustment for confounding factors, iodine excretion was significantly associated with intakes of kelp and soup stock from kelp and fish. Conclusions Although multiple measurements for urinary iodine are required to confirm our results, this study showed the current iodine status of healthy Japanese adults. The results suggest that kelp and fish are the main contributors to Japanese iodine status measured by 24-hour urine. PMID:27374137

Increased urinary excretion of thioether in new rubber workers

PubMed Central

Kilpikari, I; Savolainen, H

1982-01-01

ABSTRACT Urinary excretion of thioether before starting work and in the early work period in a rubber factory was measured in urine samples collected after one, two to four, and five or more months of starting work. The study population consisted of 84 new workers. The urinary excretion of thioether decreased after one month's exposure and increased thereafter up to five months. Measurement of urinary thioethers in groups of new workers is therefore informative of exposure to alkylating agents only after several months from starting work. This effect may be mediated by the induction of the pertinent metabolic pathway. PMID:7138800

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

PubMed Central

Vinci, Joseph M.; Gill, John R.; Bowden, Robert E.; Pisano, John J.; Izzo, Joseph L.; Radfar, Nazam; Taylor, Addison A.; Zusman, Randall M.; Bartter, Frederic C.; Keiser, Harry R.

1978-01-01

The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3±5.3 (S.E.M.) ng/ml per h to 3.3±1.1 ng/ml per h, mean plasma bradykinin (patients recumbent) from 15.4±4.4 ng/ml to 3.9±0.9 ng/ml, mean urinary kallikrein excretion from 24.8±3.2 tosyl-arginine-methyl ester units (TU)/day to 12.4±2.0 TU/day, but increased mean urinary kinin excretion from 3.8±1.3 μg/day to 8.5±2.5 μg/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for urinary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The results suggest that, in Bartter's syndrome, prostaglandins mediate the low urinary kinins and the high plasma bradykinin, and that urinary kallikrein, which is aldosterone dependent, does not control kinin excretion. The high plasma bradykinin may be a cause of the pressor hyporesponsiveness to angiotensin II which characterizes the syndrome. PMID:96139

Increased Klk9 Urinary Excretion Is Associated to Hypertension-Induced Cardiovascular Damage and Renal Alterations

PubMed Central

Blázquez-Medela, Ana M.; García-Sánchez, Omar; Quirós, Yaremi; Blanco-Gozalo, Victor; Prieto-García, Laura; Sancho-Martínez, Sandra M.; Romero, Miguel; Duarte, Juan M.; López-Hernández, Francisco J.; López-Novoa, José M.; Martínez-Salgado, Carlos

2015-01-01

Abstract Early detection of hypertensive end-organ damage and secondary diseases are key determinants of cardiovascular prognosis in patients suffering from arterial hypertension. Presently, there are no biomarkers for the detection of hypertensive target organ damage, most outstandingly including blood vessels, the heart, and the kidneys. We aimed to validate the usefulness of the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9) as a biomarker of hypertension-induced target organ damage. Urinary, plasma, and renal tissue levels of KLK9 were measured by the Western blot in different rat models of hypertension, including angiotensin-II infusion, DOCA-salt, L-NAME administration, and spontaneous hypertension. Urinary levels were associated to cardiovascular and renal injury, assessed by histopathology. The origin of urinary KLK9 was investigated through in situ renal perfusion experiments. The urinary excretion of KLK9 is increased in different experimental models of hypertension in rats. The ACE inhibitor trandolapril significantly reduced arterial pressure and the urinary level of KLK9. Hypertension did not increase kidney, heart, liver, lung, or plasma KLK9 levels. Hypertension-induced increased urinary excretion of KLK9 results from specific alterations in its tubular reabsorption, even in the absence of overt nephropathy. KLK9 urinary excretion strongly correlates with cardiac hypertrophy and aortic wall thickening. KLK9 appears in the urine in the presence of hypertension as a result of subtle renal handling alterations. Urinary KLK9 might be potentially used as an indicator of hypertensive cardiac and vascular damage. PMID:26469898

Monitoring ovarian cycle activity via progestagens in urine and feces of female mountain gorillas: A comparison of EIA and LC-MS measurements.

PubMed

Habumuremyi, Sosthene; Robbins, Martha M; Fawcett, Katie A; Deschner, Tobias

2014-02-01

Understanding the reproductive biology of endangered mountain gorillas (Gorilla beringei beringei) is essential for optimizing conservation strategies, determining any demographic impact of socioecological changes, and providing information for comparative studies of primates. Non-invasive techniques have been used to assess the reproductive function of many primates and the importance of validating the measurements of hormones metabolites is widely recognized because they may vary even within closely related species. To determine if it is possible to non-invasively monitor ovarian activity in wild mountain gorillas, we used enzyme immunoassays (EIA) to quantify both urinary and fecal excretion of immunoreactive pregnanediol-3-glucuronide (iPdG), defined as all metabolites detected by a pregnanediol-3-glucuronide immunoassay (PdG EIA). Simultaneously, we performed the liquid chromatography mass spectrometry (LC-MS) to quantify the excretion of pregnanediol in urine and feces. Samples were analyzed over nine cycles of five females from the habituated gorillas monitored by Karisoke Research Center, Rwanda. As an additional indicator for ovulation timing, estrone conjugates (E1C) were measured in a subset of urine samples. The concentrations of iPdG and pregnanediol measured in the same samples were significantly correlated. Urinary concentrations of iPdG and pregnanediol fluctuated over the menstrual cycle but did not reveal any cyclic pattern, whereas a typical preovulatory urinary E1C surge and postovulatory increases of fecal iPdG and pregnanediol were detected. The luteal peaks of iPdG and pregnanediol levels in feces were on average 2.8 and 7.6 times higher, respectively, than averaged levels in the corresponding follicular phase. The relative number of days with observed matings was higher within the presumed fertile window than in the preceding period. Overall, the results indicate that fecal analysis of iPdG and pregnanediol is suitable for detecting ovulation in female mountain gorillas. Urinary measurements using both EIA and LC-MS appeared to be uninformative for monitoring ovarian activity in this primate. © 2013 Wiley Periodicals, Inc.

Boldenone, boldione, and milk replacers in the diet of veal calves: the effects of phytosterol content on the urinary excretion of boldenone metabolites.

PubMed

Gallina, G; Ferretti, G; Merlanti, R; Civitareale, C; Capolongo, F; Draisci, R; Montesissa, C

2007-10-03

Twenty-six veal calves were split into two groups and fed two milk replacers with a different content of phytosterols for 26 days; then, 14 calves (7 animals from each diet) were kept as controls and 12 calves (6 per diet) received daily, per os, a combination of 17beta-boldenone (17beta-Bol) and androsta-1,4-dien-3,17-dione (ADD) for 38 days. The urinary elimination of 17 alpha-/17beta-boldenone conjugates (17 alpha/beta-Bol) and androsta-1,4-dien-3,17-dione (ADD) was followed by liquid chromatography-tandem mass spectrometry from all of the animals until slaughtering. In urine from treated animals, 17 alpha-Bol concentrations, despite a great variability, were greater than 17beta-Bol, both detected always as conjugates. At days 1, 2, and 3, the mean urine concentration of 17 alpha-Bol was higher than 12 ng/mL. A remarkable decrease was observed during the following days, but the 17 alpha-Bol concentration was still higher than the attention level of 2 ng/mL in 58% of the samples; the concentration of 17beta-Bol was around the action level of 1 ng/mL; two days after treatment withdrawal, no 17beta-Bol was detected in the urine. In urine from control animals, the 17 alpha-Bol concentration was strictly related to the phytosterol content of the diet, while, in urine from treated animals, the much higher 17 alpha-Bol levels were not modified by the production from diet precursors. The results confirmed that a 17 alpha-Bol level higher than 2 ng/mL should be considered as evidence of suspected illegal treatment and that the urinary excretion of 17beta-Bol is due to exogenous administration of 17beta-Bol. The discontinuous rate of elimination of both 17 alpha- and 17beta-Bol, despite the daily administration of 17beta-Bol plus ADD, indicates the necessity for further research to detect other urinary boldenone metabolites to strength surveillance strategy.

Technical Basis Document: A Statistical Basis for Interpreting Urinary Excretion of Plutonium Based on Accelerator Mass Spectrometry (AMS) for Selected Atoll Populations in the Marshall Islands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogen, K; Hamilton, T F; Brown, T A

2007-05-01

We have developed refined statistical and modeling techniques to assess low-level uptake and urinary excretion of plutonium from different population group in the northern Marshall Islands. Urinary excretion rates of plutonium from the resident population on Enewetak Atoll and from resettlement workers living on Rongelap Atoll range from <1 to 8 {micro}Bq per day and are well below action levels established under the latest Department regulation 10 CFR 835 in the United States for in vitro bioassay monitoring of {sup 239}Pu. However, our statistical analyses show that urinary excretion of plutonium-239 ({sup 239}Pu) from both cohort groups is significantly positivelymore » associated with volunteer age, especially for the resident population living on Enewetak Atoll. Urinary excretion of {sup 239}Pu from the Enewetak cohort was also found to be positively associated with estimates of cumulative exposure to worldwide fallout. Consequently, the age-related trends in urinary excretion of plutonium from Marshallese populations can be described by either a long-term component from residual systemic burdens acquired from previous exposures to worldwide fallout or a prompt (and eventual long-term) component acquired from low-level systemic intakes of plutonium associated with resettlement of the northern Marshall Islands, or some combination of both.« less

The relationship between sodium excretion and blood pressure, urine albumin, central retinal arteriolar equivalent.

PubMed

Huang, Feng; Yu, Peng; Yuan, Yin; Li, Qiaowei; Lin, Fan; Gao, Zhonghai; Chen, Falin; Zhu, Pengli

2016-10-11

Many studies showed an association between dietary salt intake, blood pressure and increased CVD risk. The potential reason may be related to vascular structural and functional changes, through alterations in endothelial function. The central retinal arteriolar equivalent and urinary albumin reflected vascular endothelial dysfunction in different part of the body. The urinary sodium-creatinine ratio of causal urine specimens could represent the 24-h urinary sodium intake to estimate sodium intake. The 24-h sodium excretion was estimated by urinary sodium-creatinine ratio. Urinary albumin-creatinine ratio (UACR), reflecting renal arterial damage, was also determined. The central retinal arteriolar equivalent (CRAE) was detected by fundus photography and was further analyzed by semi-quantitative software. Participants included 951 hypertensive patients with the average sodium excretion of 11.62 ± 3.01 g. The sodium excretion was significantly higher (P < 0.01) in the hypertensive as compared to that of the non-hypertensive participants. Prevalence of hypertension was increased with increasing sodium excretion. The sodium excretion was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively (r = 0.20 and 0.14; P < 0.01). Furthermore, UACR and CRAE were significantly (P < 0.01) different within the sodium excretion quartiles (Q1-Q4). After adjusting the confounding variables, such as age and sex, the binary logistic regression analysis showed that sodium excretion was an independent factor of UACR and CRAE (P < 0.01). Our results suggest that sodium excretion in the hypertensive participants were higher. The high sodium excretion was related with the renal arterial damage as well as retinal arteriolar changes.

Pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe (Part I).

PubMed

Asami, Akitoshi; Shimada, Tsutomu; Mizuhara, Yasuharu; Asano, Takayuki; Takeda, Shuichi; Aburada, Takashi; Miyamoto, Ken-Ichi; Aburada, Masaki

2010-07-01

To investigate the pharmacokinetics of [6]-shogaol, a pungent ingredient of Zingiber officinale Roscoe, the pharmacokinetic parameters were determined by using (14)C-[6]-shogaol (labeled compound) and [6]-shogaol (non-labeled compound). When the labeled compound was orally administered to rats, the maximum plasma concentration (C (max)) and the area under the curve (AUC) of plasma radioactivity concentration increased in a dose-dependent manner. When the labeled compound was orally administered at a dose of 10 mg/kg, 20.0 + or - 1.8% of the radioactivity administered was excreted into urine, 64.0 + or - 12.9% into feces, and 0.2 + or - 0.1% into breath. Thus, more of the radioactivity was excreted into feces than into urine, and almost no radioactivity was excreted into breath. Furthermore, when the labeled compound was orally administered at a dose of 10 mg/kg, cumulative biliary radioactivity excretion over 48 h was 78.5 + or - 4.5% of the radioactivity administered, and cumulative urinary radioactivity excretion over 48 h was 11.8 + or - 2.7%, showing that about 90% of the dose administered orally was absorbed from the digestive tract and most of the fecal excretion was via biliary excretion. On the other hand, when the non-labeled compound [6]-shogaol was orally administered, the plasma concentration and biliary excretion of the unchanged form were extremely low. When these results are combined with those obtained with the labeled compound, it would suggest that [6]-shogaol is mostly metabolized in the body and excreted as metabolites.

Contribution of dietary oxalate to urinary oxalate excretion

NASA Technical Reports Server (NTRS)

Holmes, R. P.; Goodman, H. O.; Assimos, D. G.

2001-01-01

BACKGROUND: The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and stone formation. Dietary oxalate is believed to make only a minor (10 to 20%) contribution to the amount of oxalate excreted in urine, but the validity of the experimental observations that support this conclusion can be questioned. An understanding of the actual contribution of dietary oxalate to urinary oxalate excretion is important, as it is potentially modifiable. METHODS: We varied the amount of dietary oxalate consumed by a group of adult individuals using formula diets and controlled, solid-food diets with a known oxalate content, determined by a recently developed analytical procedure. Controlled solid-food diets were consumed containing 10, 50, and 250 mg of oxalate/2500 kcal, as well as formula diets containing 0 and 180 mg oxalate/2500 kcal. Changes in the content of oxalate and other ions were assessed in 24-hour urine collections. RESULTS: Urinary oxalate excretion increased as dietary oxalate intake increased. With oxalate-containing diets, the mean contribution of dietary oxalate to urinary oxalate excretion ranged from 24.4 +/- 15.5% on the 10 mg/2500 kcal/day diet to 41.5 +/- 9.1% on the 250 mg/2500 kcal/day diet, much higher than previously estimated. When the calcium content of a diet containing 250 mg of oxalate was reduced from 1002 mg to 391 mg, urinary oxalate excretion increased by a mean of 28.2 +/- 4.8%, and the mean dietary contribution increased to 52.6 +/- 8.6%. CONCLUSIONS: These results suggest that dietary oxalate makes a much greater contribution to urinary oxalate excretion than previously recognized, that dietary calcium influences the bioavailability of ingested oxalate, and that the absorption of dietary oxalate may be an important factor in calcium oxalate stone formation.

Factitious Cushing's syndrome masquerading as Cushing's disease.

PubMed

Thynne, Tilenka; White, Graham H; Burt, Morton G

2014-03-01

Factitious Cushing's syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing's syndrome difficult. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200 nmol/24 h. Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and IPSS. This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis. © 2013 John Wiley & Sons Ltd.

Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics.

PubMed

Riba, Jordi; Valle, Marta; Urbano, Gloria; Yritia, Mercedes; Morte, Adelaida; Barbanoj, Manel J

2003-07-01

The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting beta-carboline alkaloids (harmine, harmaline, and tetrahydroharmine). Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

Controlled exercise effects on chromium excretion of trained and untrained runners consuming a constant diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, R.A.; Bryden, N.A.; Polansky, M.M.

1986-03-05

To determine if degree of training effects urinary Cr losses, Cr excretion of 8 adult trained and 5 untrained runners was determined on rest days and following exercise at 90% of maximal oxygen uptake on a treadmill to exhaustion with 30 second exercise and 30 second rest periods. Subjects were fed a constant daily diet containing 9 ..mu..g of Cr per 1000 calories to minimize changes due to diet. Maximal oxygen consumption of the trained runners was in the good or above range based upon their age and that of the untrained runners was average or below. While consuming themore » control diet, basal urinary Cr excretion of subjects who exercise regularly was significantly lower than that of the sedentary control subjects, 0.09 +/- 0.01 and 0.21 +/- 0.03 ..mu..g/day (mean +/- SEM), respectively. Daily urinary Cr excretion of trained subjects was significantly higher on the day of a single exercise bout at 90% of maximal oxygen consumption compared to nonexercise days, 0.12 +/- 0.02 and 0.09 +/- 0.01 ..mu..g/day, respectively. Urinary Cr excretion of 5 untrained subjects was not altered following controlled exercise. These data demonstrate that basal urinary Cr excretion and excretion in response to exercise are related to maximal oxygen consumption and therefore degree of fitness.« less

Metabolism of methyltestosterone in the greyhound.

PubMed

Biddle, S T B; O'Donnell, A; Houghton, E; Creaser, C

2009-03-01

Gas chromatography/mass spectrometry and selective derivatisation techniques have been used to identify urinary metabolites of methyltestosterone following oral administration to the greyhound. Several metabolites were identified including reduced, mono-, di- and trihydroxylated steroids. The major metabolites observed were 17alpha-methyl-5beta-androstane-3alpha-17beta-diol, 17alpha-methyl-5beta-androstane-3alpha,16alpha,17beta-triol, and a further compound tentatively identified as 17alpha-methyl-5z-androstane-6z,17beta-triol. The most abundant of these was the 17alpha-methyl-5beta-androstane-3alpha,16alpha,17beta-triol. This metabolite was identified by comparison with a reference standard synthesised using a Grignard procedure and characterised using trimethylsilyl (TMS) and acetonide-TMS derivatisation techniques. There did not appear to be any evidence for 16beta-hydroxylation as a phase I metabolic transformation in the greyhound. However, significant quantities of 16alpha-hydroxy metabolites were detected. Selective enzymatic hydrolysis procedures indicated that the major metabolites identified were excreted as glucuronic acid conjugates. Metabolic transformations observed in the greyhound have been compared with those of other mammalian species and are discussed here. John Wiley & Sons, Ltd

Assessment of renal dopaminergic system activity during cyclosporine A administration in the rat.

PubMed Central

Pestana, M.; Vieira-Coelho, M. A.; Pinto-do-O, P. C.; Fernandes, M. H.; Soares-da-Silva, P.

1995-01-01

1. Administration of cyclosporine A (CsA; 50 mg kg-1 day-1, s.c.) for 14 days produced an increase in both systolic (SBP) and diastolic (DBP) blood pressure by 60 and 25 mmHg, respectively. The urinary excretion of dopamine, DOPAC and HVA was reduced from day 5-6 of CsA administration onwards (dopamine from 19 to 46%, DOPAC from 16 to 48%; HVA from 18 to 42%). In vehicle-treated rats, the urinary excretion of dopamine and DOPAC increased (from 7 to 60%) from day 5 onwards; by contrast, the urinary excretion of HVA was reduced (from 27 to 60%) during the second week. 2. No significant difference was observed between the Vmax and Km values of renal aromatic L-amino acid decarboxylase (AAAD) in rats treated with CsA for 7 and 14 days or with vehicle. 3. Km and Vmax of monoamine oxidase types A and B did not differ significantly between rats treated with CsA for 7 and 14 days or with vehicle. 4. Maximal catechol-O-methyltransferase activity (Vmax) in homogenates of renal tissues obtained from rats treated with CsA for 7 or 14 days was significantly higher than that in vehicle-treated rats; Km (22.3 +/- 1.5 microM) values for COMT did not differ between the three groups of rats. 5. The accumulation of newly-formed dopamine and DOPAC in cortical tissues of rats treated with CsA for 14 days was three to four times higher than in controls. The outflow of both dopamine and DOPAC declined progressively with time and reflected the amine and amine metabolite tissue contents. No significant difference was observed between the DOPAC/dopamine ratios in the perifusate of renal tissues obtained from CsA- and vehicle-treated rats. In addition, no significant differences were observed in k values or in the slope of decline of both DA and DOPAC between experiments performed with CsA and vehicle-treated animals. 6. The Vmax for the saturable component of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake in renal tubules from rats treated with CsA was twice that of vehicle-treated animals. Km in CsA- and vehicle-treated rats did not differ. 7. The decrease in the urinary excretion of sodium and an increase in blood pressure during CsA treatment was accompanied by a reduction in daily urinary excretion of dopamine. This appears to result from a reduction in the amount of L-DOPA made available to the kidney and does not involve changes in tubular AAAD, the availability of dopamine to leave the renal cells and dopamine metabolism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8564191

Deficiency of renal dopaminergic-dependent natriuretic response to acute sodium load in black salt-sensitive subjects in contrast to salt-resistant subjects.

PubMed

Damasceno, A; Santos, A; Serrão, P; Caupers, P; Soares-da-Silva, P; Polónia, J

1999-12-01

To evaluate the involvement of the renal dopaminergic system in the natriuretic responses to acute saline load in salt-resistant (SR) and salt-sensitive (SS) black normotensive (NT) and hypertensive (HT) subjects. We studied the relationship between the urinary excretion of dopa, dopamine (DA) and its metabolite DOPAC and the natriuretic responses to acute volume expansion (2 l NaCl 0.9% over 2 h) in 20 black NT subjects (12 SR and 8 SS) and 19 black HT subjects (10 SS and 9 SR). Subjects received a low salt (LS) diet (40 mmol sodium/day) for 1 week and a high salt (HS) diet (300 mmol sodium/day) for 1 week; the sequence of the dietary regimens was randomized. Comparisons were made between the results before the saline infusion (baseline) and the results 2 h after the infusion. In all the groups saline infusion induced significant increases in urinary volume (ml/4 h) of two- to three-fold and in urinary sodium excretion (mmol/4 h) of three- to ten-fold; these increases were significantly greater during the HS diet than during the LS diet. Saline infusion significantly increased the mean arterial pressure (MAP) by 5 mmHg in HT-SS subjects and by 4-5 mmHg in NT-SS subjects, but the MAP did not changed in the NT-SR and HT-SR groups. Under the LS diet, saline infusion changed the DA excretion (in nmol/4 h) by -49+/-89 in HT-SS subjects, by 17+/-52 in NT-SS subjects, by 235+/-72 in HT-SR subjects and by 220+/-86 in NT-SR subjects (P < 0.05 between SR and SS subjects). The saline infusion-induced changes in DA excretion correlated significantly with the increases in urinary sodium excretion (r = 0.71, P < 0.01) in the NT-SR and HT-SR subjects under the LS diet, but not in the SR groups on the HS diet nor in the SS groups (HT and NT) on either diet. Saline infusion significantly reduced the DA/dopa ratio in SS (NT and HT) but not SR (NT and HT) subjects, whereas the DA/DOPAC (dihydroxyphenylacetic acid) ratios were similar in all the groups. The urinary dopaminergic system may participate in the natriuretic responses to acute sodium load only in SR subjects (NT and HT) and only under LS diets, but not in SS subjects (NT and HT). This strongly suggests that black NT- and HT-SS subjects have an underlying impairment in the activity of the renal dopaminergic system which may be associated with a reduced decarboxylation of dopa into DA.

Single ingestion of di-(2-propylheptyl) phthalate (DPHP) by male volunteers: DPHP in blood and its metabolites in blood and urine.

PubMed

Klein, D; Kessler, W; Pütz, C; Semder, B; Kirchinger, W; Langsch, A; Gries, W; Otter, R; Gallien, A K E; Wurzenberger, X; Filser, J G

2018-05-11

Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). All curves were characterized by an invasion and an elimination phase the kinetic parameters of which were determined together with the areas under the concentration-time curves in blood (AUCs). AUCs were: DPHP > MPHP > oxo-MPHP > OH-MPHP. The amounts excreted in urine were: oxo-MPHP > OH-MPHP> > cx-MPHP > MPHP. The AUCs of MPHP, oxo-MPHP, or OH-MPHP could be estimated well from the cumulative amounts of urinary OH-MPHP or oxo-MPHP excreted within 22 h after DPHP intake. Not considering possible differences in species-sensitivity towards unconjugated DPHP metabolites, it was concluded from a comparison of their AUCs in DPHP-exposed humans with corresponding earlier data in rats that there is no increased risk of adverse effects associated with the internal exposure of unconjugated DPHP metabolites in humans as compared to rats when receiving the same dos of DPHP per kg body weight. Copyright © 2018. Published by Elsevier B.V.

Optimization of solid-phase extraction and liquid chromatography-tandem mass spectrometry for simultaneous determination of capilliposide B and its active metabolite in rat urine and feces: Overcoming nonspecific binding.

PubMed

Cheng, Zhongzhe; Zhou, Xing; Li, Wenyi; Hu, Bingying; Zhang, Yang; Xu, Yong; Zhang, Lin; Jiang, Hongliang

2016-11-30

Capilliposide B, a novel oleanane triterpenoid saponin isolated from Lysimachia capillipes Hemsl, showed significant anti-tumor activities in recent studies. To characterize the excretion of Capilliposide B, a reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of Capilliposide B and its active metabolite, Capilliposide A in rat urine and feces. Sample preparation using a solid-phase extraction procedure was optimized by acidification of samples at various degrees, providing extensive sample clean-up with a high extraction recovery. In addition, rat urinary samples were pretreated with CHAPS, an anti-adsorptive agent, for overcoming nonspecific analytes adsorption during sample storage and process. The method validation was conducted over the curve range of 10.0-5000ng/ml for both analytes. The intra- and inter-day precision and accuracy of the QC samples showed ≤11.0% RSD and -10.4-12.8% relative error. The method was successfully applied to an excretion study of Capilliposide B following intravenous administration. Copyright © 2016 Elsevier B.V. All rights reserved.

Urinary Fluoride Concentration in Children with Disabilities Following Long-Term Fluoride Tablet Ingestion

ERIC Educational Resources Information Center

Liu, Hsiu-Yueh; Chen, Jung-Ren; Hung, Hsin-Chia; Hsiao, Szu-Yu; Huang, Shun-Te; Chen, Hong-Sen

2011-01-01

Urine is the most commonly utilized biomarker for fluoride excretion in public health and epidemiological studies. Approximately 30-50% of fluoride is excreted from urine in children. Urinary fluoride excretion reflects the total fluoride intake from multiple sources. After administering fluoride tablets to children with disabilities, urinary…

Bioavailability of orange juice (poly)phenols: the impact of short-term cessation of training by male endurance athletes.

PubMed

Pereira-Caro, Gema; Polyviou, Thelma; Ludwig, Iziar A; Nastase, Ana-Maria; Moreno-Rojas, José Manuel; Garcia, Ada L; Malkova, Dalia; Crozier, Alan

2017-09-01

Background: Physical exercise has been reported to increase the bioavailability of citrus flavanones. Objective: We investigated the bioavailability of orange juice (OJ) (poly)phenols in endurance-trained males before and after cessation of training for 7 d. Design: Ten fit, endurance-trained males, with a mean ± SD maximal oxygen consumption of 58.2 ± 5.3 mL · kg -1 · min -1 , followed a low (poly)phenol diet for 2 d before drinking 500 mL of OJ containing 398 μmol of (poly)phenols, of which 330 μmol was flavanones. After the volunteers stopped training for 7 d the feeding study was repeated. Urine samples were collected 12 h pre- and 24 h post-OJ consumption. Bioavailability was assessed by the quantitative analysis of urinary flavanone metabolites and (poly)phenol catabolites with the use of high-pressure liquid chromatography-high resolution mass spectrometry. Results: During training, 0-24-h urinary excretion of flavanone metabolites, mainly hesperetin-3'- O -glucuronide, hesperetin-3'-sulfate, naringenin-4'- O -glucuronide, naringenin-7- O -glucuronide, was equivalent to 4.2% of OJ flavanone intake. This increased significantly to 5.2% when OJ was consumed after the volunteers stopped training for 7 d. Overall, this trend, although not significant, was also observed with OJ-derived colonic catabolites, which, after supplementation in the trained state, were excreted in amounts equivalent to 51% of intake compared with 59% after cessation of training. However, urinary excretion of 3 colonic catabolites of bacterial origin, most notably, 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic acid, did increase significantly when OJ was consumed postcessation compared with precessation of training. Data were also obtained on interindividual variations in flavanone bioavailability. Conclusions: A 7-d cessation of endurance training enhanced, rather than reduced, the bioavailability of OJ flavanones. The biological significance of these differences and whether they extend to the bioavailability of other dietary (poly)phenols remain to be determined. Hesperetin-3'- O -glucuronide and the colonic microbiota-derived catabolite 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic acid are key biomarkers of the consumption of hesperetin- O -glycoside-containing OJ and other citrus products. This trial was registered at clinicaltrials.gov as NCT02627547. © 2017 American Society for Nutrition.

An Ultrahigh-Performance Liquid Chromatography-Time-of-Flight Mass Spectrometry Metabolomic Approach to Studying the Impact of Moderate Red-Wine Consumption on Urinary Metabolome.

PubMed

Esteban-Fernández, Adelaida; Ibañez, Clara; Simó, Carolina; Bartolomé, Begoña; Moreno-Arribas, M Victoria

2018-04-06

Moderate red-wine consumption has been widely described to exert several benefits in human health. This is mainly due to its unique content of bioactive polyphenols, which suffer several modifications along their pass through the digestive system, including microbial transformation in the colon and phase-II metabolism, until they are finally excreted in urine and feces. To determine the impact of moderate wine consumption in the overall urinary metabolome of healthy volunteers ( n = 41), samples from a red-wine interventional study (250 mL/day, 28 days) were investigated. Urine (24 h) was collected before and after intervention and analyzed by an untargeted ultrahigh-performance liquid chromatography-time-of-flight mass spectrometry metabolomics approach. 94 compounds linked to wine consumption, including specific wine components (tartaric acid), microbial-derived phenolic metabolites (5-(dihydroxyphenyl)-γ-valerolactones and 4-hydroxyl-5-(phenyl)-valeric acids), and endogenous compounds were identified. Also, some relationships between parallel fecal and urinary metabolomes are discussed.

Productive performance and urinary excretion of mimosine metabolites by hair sheep grazing in a silvopastoral system with high densities of Leucaena leucocephala.

PubMed

Barros-Rodríguez, Marcos; Solorio-Sánchez, Javier; Ku-Vera, Juan; Ayala-Burgos, Armín; Sandoval-Castro, Carlos; Solís-Pérez, Georgina

2012-12-01

The aim of this study was to evaluate daily weight gain (DWG), total dry matter (DM) intake, rumen degradability of forage, and urinary excretion of mimosine metabolites by hair sheep in a silvopastoral system with high densities of Leucaena leucocephala. A completely randomized design was carried out with two treatments: treatment 1 (T1) silvopastoral system with leucaena at a density of 35,000 plants/ha and treatment 2 (T2), leucaena at a density of 55,000 plants/ha. Leucaena was associated with tropical grasses Panicum maximum and Cynodon nlemfluensis. Twenty-four male Pelibuey lambs of 23.2 ± 3.4 kg live weight (LW) were used (12 lambs per treatment). Results showed differences (P < 0.05) in DWG of T1 (106.41 ± 11.66 g(-1) sheep(-1)) with respect to that of T2 (81.33 ± 11.81 g(-1) sheep). Voluntary intake was higher in lambs from T1 (83.81 ± 04.07 g DM/kg LW(0.75)) with respect to that from T2 (71.67 ± 8.12 g DM/kg LW(0.75)). There was a difference in color of urine between sheep of T1 and T2, the latter giving positive results for the presence of metabolites derived from mimosine (3-4 dihydroxypyridine and 2-3 dihydroxy pyridone). Rumen degradability of DM of L. leucocephala was higher (P < 0.05) compared to that of P. maximum and C. nlemfluensis (72.94 ± 0.40 vs. 67.06 ± 1.50 and 63.25 ± 1.51 %, respectively). It is concluded that grazing at high densities of L. leucocephala affects daily weight gain of hair sheep, possibly due to ingestion of high amounts of mimosine which may exert an adverse effect on voluntary intake.

Urinary isoflavonoid excretion as a biomarker of dietary soy intake during two randomized soy trials

PubMed Central

Morimoto, Yukiko; Beckford, Fanchon; Franke, Adrian A.; Maskarinec, Gertraud

2014-01-01

We evaluated urinary isoflavonoid excretion as a biomarker of dietary isoflavone intake during two randomized soy trials (13–24 months) among 256 premenopausal women with a total of 1,385 repeated urine samples. Participants consumed a high-soy diet (2 servings/day) and a low-soy diet (<3 servings/week), completed 7 unannounced 24-hour dietary recalls, and donated repeated urine samples, which were analyzed for isoflavonoid excretion by liquid chromatography methods. We computed correlation coefficients and applied logistic regression to estimate the area under the curve. Median daily dietary isoflavone intakes at baseline, during low- and high-soy diet were 0.5, 0.2, and 67.7 mg aglycone equivalents, respectively. The corresponding urinary isoflavonoid excretion values were 0.9, 1.1, and 43.9 nmol/mg creatinine. Across diets, urinary isoflavonoid excretion was significantly associated with dietary isoflavone intake (rs=0.51, AUC=0.85; p<0.0001) but not within diet periods (rs=0.05–0.06, AUC=0.565–0.573). Urinary isoflavonoid excretion is an excellent biomarker to discriminate between low- and high-soy diets across populations, but the association with dietary isoflavone intake is weak when the range of soy intake is small. PMID:24901088

Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria.

PubMed

Kovacevic, Larisa; Lu, Hong; Caruso, Joseph A; Govil-Dalela, Tuhina; Thomas, Ronald; Lakshmanan, Yegappan

2017-06-01

Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters. Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples. Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r = 0.77, p < 0.001), and FABPL (r = 0.80, p = 0.005). We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.

Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function

PubMed Central

Haneda, Masakazu; Koya, Daisuke; Kondo, Keiko; Tanaka, Sachiko; Arima, Hisatomi; Kume, Shinji; Nakazawa, Jun; Chin-Kanasaki, Masami; Ugi, Satoshi; Kawai, Hiromichi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi

2015-01-01

Background and objectives We investigated the association of urinary potassium and sodium excretion with the incidence of renal failure and cardiovascular disease in patients with type 2 diabetes. Design, setting, participants, & measurements A total of 623 Japanese type 2 diabetic patients with eGFR≥60 ml/min per 1.73 m2 were enrolled in this observational follow-up study between 1996 and 2003 and followed-up until 2013. At baseline, a 24-hour urine sample was collected to estimate urinary potassium and sodium excretion. The primary end point was renal and cardiovascular events (RRT, myocardial infarction, angina pectoris, stroke, and peripheral vascular disease). The secondary renal end points were the incidence of a 50% decline in eGFR, progression to CKD stage 4 (eGFR<30 ml/min per 1.73 m2), and the annual decline rate in eGFR. Results During the 11-year median follow-up period, 134 primary end points occurred. Higher urinary potassium excretion was associated with lower risk of the primary end point, whereas urinary sodium excretion was not. The adjusted hazard ratios for the primary end point in Cox proportional hazards analysis were 0.56 (95% confidence interval [95% CI], 0.33 to 0.95) in the third quartile of urinary potassium excretion (2.33–2.90 g/d) and 0.33 (95% CI, 0.18 to 0.62) in the fourth quartile (>2.90 g/d) compared with the lowest quartile (<1.72 g/d). Similar associations were observed for the secondary renal end points. The annual decline rate in eGFR in the fourth quartile of urinary potassium excretion (–1.3 ml/min per 1.73 m2/y; 95% CI, –1.5 to –1.0) was significantly slower than those in the first quartile (–2.2; 95% CI, –2.4 to –1.8). Conclusions Higher urinary potassium excretion was associated with the slower decline of renal function and the lower incidence of cardiovascular complications in type 2 diabetic patients with normal renal function. Interventional trials are necessary to determine whether increasing dietary potassium is beneficial. PMID:26563378

Concentrations of nandrolone metabolites in urine after the therapeutic administration of an ophthalmic solution.

PubMed

Avois, Lidia; Mangin, Patrice; Saugy, Martial

2007-05-09

Nandrolone, an anabolic steroid, is used for the treatment of several diseases and is available in various pharmaceutical formulations. The most widely used pharmaceutical formulation is Deca-Durabolin, but other products, such as Keratyl eye drops solution, are also currently administered. Nandrolone is one of the most abused anabolic steroid in sports. Analyses for this anabolic steroid according to the World Anti-Doping Agency (WADA) protocol are based on the identification of the nandrolone two main urinary metabolites which, in humans, are glucuronides of 19-norandrosterone and 19-noretiocholanolone. A positive cut off limit of 2 ng/mL has been set by the anti-doping code for the first metabolite, 19-norandrosterone. In this preliminary study, an eye drops solution (Keratyl) containing a therapeutic dose of a nandrolone sodium sulphate was administered to several male volunteers during 3 days and urines were collected during 3 weeks. Surprisingly, contrary to all expectations, the urinary concentrations measured in urines reached 450 ng/mL and 70 ng/mL for norandrosterone and noretiocholanolone, respectively. Moreover, concentration levels near to 2 ng/mL were found, more than 2 weeks after the last administration, depending on individual metabolism. Inter-variability as well as intra-variability of nandrolone excretion kinetic, regarding this particular administration mode, were also evaluated. Quantification of nandrolone metabolites was performed by GC-MS. The method was previously validated in terms of specificity, precision, linearity, LOD, LOQ, robustness, accuracy and the expanded uncertainty was also evaluated.

Urinary potassium excretion and risk of cardiovascular events.

PubMed

Kieneker, Lyanne M; Gansevoort, Ron T; de Boer, Rudolf A; Brouwers, Frank P; Feskens, Edith Jm; Geleijnse, Johanna M; Navis, Gerjan; Bakker, Stephan Jl; Joosten, Michel M

2016-05-01

Observational studies on dietary potassium and risk of cardiovascular disease (CVD) have reported weak-to-modest inverse associations. Long-term prospective studies with multiple 24-h urinary samples for accurate estimation of habitual potassium intake, however, are scarce. We examined the association between urinary potassium excretion and risk of blood pressure-related cardiovascular outcomes. We studied 7795 subjects free of cardiovascular events at baseline in the Prevention of Renal and Vascular End-stage Disease study, a prospective, observational cohort with oversampling of subjects with albuminuria at baseline. Main cardiovascular outcomes were CVD [including ischemic heart disease (IHD), stroke, and vascular interventions], IHD, stroke, and new-onset heart failure (HF). Potassium excretion was measured in two 24-h urine specimens at the start of the study (1997-1998) and midway through follow-up (2001-2003). Baseline median urinary potassium excretion was 70 mmol/24 h (IQR: 56-84 mmol/24 h). During a median follow-up of 10.5 y (IQR: 9.9-10.8 y), a total of 641 CVD, 465 IHD, 172 stroke, and 265 HF events occurred. After adjustment for age and sex, inverse associations were observed between potassium excretion and risk [HR per each 26-mmol/24-h (1-g/d) increase; 95% CI] of CVD (0.87; 0.78, 0.97) and IHD (0.86; 0.75, 0.97), as well as nonsignificant inverse associations for risk of stroke (0.85; 0.68, 1.06) and HF (0.94; 0.80, 1.10). After further adjustment for body mass index, smoking, alcohol consumption, education, and urinary sodium and magnesium excretion, urinary potassium excretion was not statistically significantly associated with risk (multivariable-adjusted HR per 1-g/d increment; 95% CI) of CVD (0.96; 0.85, 1.09), IHD (0.90; 0.81, 1.04), stroke (1.09; 0.86, 1.39), or HF (0.99; 0.83, 1.18). No associations were observed between the sodium-to-potassium excretion ratio and risk of CVD, IHD, stroke, or HF. In this cohort with oversampling of subjects with albuminuria at baseline, urinary potassium excretion was not independently associated with a lower risk of cardiovascular events. © 2016 American Society for Nutrition.

Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques.

PubMed

Mardal, Marie; Kinyua, Juliet; Ramin, Pedram; Miserez, Bram; Van Nuijs, Alexander L N; Covaci, Adrian; Meyer, Markus R

2017-01-01

Monitoring population drug use through wastewater-based epidemiology (WBE) is a useful method to quantitatively follow trends and estimate total drug consumption in communities. Concentrations of drug biomarkers might be low in wastewater due to dilution; and therefore analysis of pooled urine (PU) is useful to detect consumed drugs and identify targets of illicit drugs use. The aims of the study were (1) to screen PU and urinated soil (US) samples collected at festivals for illicit drug excretion products using hyphenated techniques; (2) to develop and validate a hydrophilic interaction liquid chromatography - mass spectrometry / mass spectrometry (HILIC-MS/MS) method of quantifying urinary targets of identified drugs in wastewater; and (3) to conduct a 24 h stability study, using PU and US to better reflect the chemical environment for targets in wastewater. Cocaine (COC) and ecstasy-like compounds were the most frequently detected illicit drugs; an analytical method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), HMMA sulfate (HMMA-S), benzoylecgonine (BE), and cocaethylene (CE) had 85-102% of initial concentration after 8 h of incubation, whereas COC and ecgonine methyl ester (EME) had 74 and 67% after 8 h, respectively. HMMA showed a net increase during 24 h of incubation (107% ± 27, n = 8), possibly due to the cleavage of HMMA conjugates, and biotransformation of MDMA. The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

PubMed

Mulder, Erik J; Anderson, George M; Kemperman, Ramses F J; Oosterloo-Duinkerken, Alida; Minderaa, Ruud B; Kema, Ido P

2010-01-01

A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production. (c) 2009 S. Karger AG, Basel.

Effect of monofluoroacetate on renal H+ excretion in the rat.

PubMed

Simonnet, H; Gauthier, C; Pellet, M V

1979-05-01

In order to investigate the effect of monofluoroacetate (MFA) on renal H+ excretion, anesthetized rats under mannitol diuresis were given intraperitoneally MFA and some of the acido-basic status parameters were determined. Urinary pH and pCO2 did not change after MFA administration, while urinary flow rate increased. MFA induced a decrease in H+ net excretion and in ammonia excretion. Titratable acidity did not change significantly within the experiment.

Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum

PubMed Central

Feyerabend, C.; Russell, M. A. H.

1978-01-01

1 Plasma nicotine levels produced by chewing nicotine gum were compared with those obtained by cigarette smoking under conditions of controlled urinary pH. 2 Although absorption was slower, plasma levels comparable to cigarette smoking were built up on 4 mg (but not 2 mg) nicotine gum. 3 Urinary excretion of nicotine was influenced markedly by pH and the rate of urine flow. 4 Plasma nicotine was higher under alkaline compared to acidic conditions (P < 0.001) but the rate of urinary nicotine excretion appeared to have little effect on the plasma level.

Carnitine status in Thai adults.

PubMed

Tanphaichitr, V; Lerdvuthisopon, N; Dhanamitta, S; Broquist, H P

1980-04-01

Plasma carnitine and urinary carnitine levels were measured in Thai adults living in Bangkok city and Ubol villages. The mean plasma carnitine and urinary carnitine levels expressed in micromoles per liter in Bangkok adults were higher than those in Ubol adults. Their mean plasma carnitine levels were 56.6 +/- 1.8 and 50.3 +/- 1.7 whereas urinary carnitine levels were 161 +/- 19 and 127 +/- 18 micromole/liter, respectively. The nutritional status in Ubol adults was inadequate. This was evidenced by the significant decrease in urinary creatinine excretion, serum albumin, and hematocrit levels. The dietary assessment agreed with the biochemical findings. Since rice, limiting in carnitine, was the main protein and energy source consumed by Ubol adults their inadequate carnitine status could be due to the low carnitine intake. Sex affects plasma carnitine levels in Bangkok adults and urinary carnitine excretion in both groups. This could be related to the lean body mass in which most of the body carnitine resides. This is supported by the higher urinary creatinine excretion in males and the significant positive correlation between carnitine excretion and creatinine-height index.

Effects of pressure on the skin exerted by clothing on responses of urinary catecholamines and cortisol, heart rate and nocturnal urinary melatonin in humans

NASA Astrophysics Data System (ADS)

Mori, Yuki; Kioka, Etsuko; Tokura, Hiromi

2002-09-01

The study investigated how the pressure exerted on the skin by clothing worn while working in the daytime affected the urinary excretion of adrenaline, noradrenaline and cortisol, heart rate, and also melatonin secretion at night. Nine young women (experiment I) and seven young women (experiment II) participated. Participants wore either a 100% cotton jacket (tight clothes, TC) or a 100% cotton T-shirt (loose clothes, LC). Loose-fitting, 100% cotton tank tops and panties were worn as underwear in both the TC and the LC groups. The main results can be summarized as follows: (1) urinary excretion of adrenaline, noradrenaline and cortisol was facilitated, and the amounts of urinary excretion were significantly higher when TC were worn. Heart rate was significantly higher in the TC group; (2) nocturnal urinary melatonin excretion was significantly greater in the TC group. These results are discussed in terms of an enhancement of diurnal sympathetic nervous system activity caused by pressure on the skin produced by tight clothing.

Winter fasting and refeeding effects on urine characteristics in white-tailed deer

USGS Publications Warehouse

DelGiudice, G.D.; Mech, L.D.; Seal, U.S.; Karns, P.D.

1987-01-01

The effects of dietary protein, fasting, and refeeding on urinary characteristics of 9 captive, female white-tailed deer (Odocoileus virginianus) were studied from 23 February to 3 May 1984. Urinary sodium (na) and potassium (K) were diminished in fasted deer after 2 and 4 weeks. Renal excretion of Na and K were lower, whereas urinary phosphorus (P) was higher in fasted deer compared to deer fed high protein-high energy (HPHE) diets. Urinary P excretion of the fasted deer was also greater than in a low protein-high energy (LPHE)-fed group. Urinary area excretion of fasted deer was similar to that of deer fed low and high protein diets. One fasted deer died during the study and exhibited notably high excretion of urea, Na, K, and calcium (Ca). No effects of the 2 levels of dietary protein on urinary characteristics were detected. Urinary Na:C and K:C ratios wer significantly correlated with Na and K intake. Urinalysis has potential as a sensitive means of monitoring the nutritional status of white-tailed deer. Data are presented as reference values for interpretation of data from deer under less controlled circumstances.

n-Hexane metabolism in occupationally exposed workers.

PubMed Central

Mutti, A; Falzoi, M; Lucertini, S; Arfini, G; Zignani, M; Lombardi, S; Franchini, I

1984-01-01

Lung uptake and excretion of n-hexane were studied in ten workers in a shoe factory. Simultaneous samples of inhaled and alveolar air were collected with the aid of a Rhan-Otis valve, personal samplers, and charcoal tubes. Alveolar excretion was monitored during a six hour postexposure period. Uptake was calculated from lung ventilation, the retention coefficient, and environmental concentrations. The amount of exhaled n-hexane was calculated from the decay curve. According to the experimental data, alveolar retention was about 25% of the inhaled n-hexane, corresponding to a lung uptake of about 17%. The postexposure alveolar excretion was about 10% of the total uptake. The main metabolites of n-hexane were identified and measured by capillary GC/MS in spot urine samples collected before, at the end, and 15 hours after the same working shift. Urinary concentrations were low, though related to n-hexane in the air. 2,5-Hexanedione in the end of shift samples gave the best estimate of overall exposure. About 3 mg/g creatinine of 2,5-hexanedione would correspond to about 50 ppm of n-hexane in the air (mean daily exposure). PMID:6498115

Application of path analysis to urinary findings of cadmium-induced renal dysfunction.

PubMed

Abe, T; Kobayashi, E; Okubo, Y; Suwazono, Y; Kido, T; Shaikh, Z A; Nogawa, K

2001-01-01

In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, beta 2-microglobulin (beta 2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure-->increase of beta 2-m and/or MT excretion-->increase of amino-N and/or total protein excretion-->increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of beta 2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

Mechanisms by which resistant starches and non-starch polysaccharide sources affect the metabolism and disposition of the food carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline.

PubMed

Kestell, P; Zhu, S; Ferguson, L R

2004-03-25

Although both non-starch polysaccharides (NSP) and resistant starches (RS) are included in current definitions of dietary fibre, our previous work has suggested fundamental differences in the way in which these two classes of material affect the disposition and absorption of a dietary carcinogen. The present studies explore whether different effects on carcinogen metabolism could play a role in the contrasting patterns seen previously. Groups of female Wistar rats were pre-fed for 4 weeks one of five types of defined diet (AIN-76). The control diet contained 35% maize starch and no dietary fibre. The RS-containing diets had all the maize starch substituted with either Hi-maize or potato starch. In the NSP-containing diets, 10% of the maize starch was substituted with dietary fibre in the form of either lignified plant cell walls (wheat straw) or soluble dietary fibre (apple pectin). Pre-fed rats were gavaged with the food carcinogen, [2-14C] 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and plasma and urinary metabolites characterized using HPLC at various time intervals after administration. After 4 h gavage, plasma from rats on both RS-containing diets contained significantly higher levels of intact IQ and lower levels of the major metabolites, IQ-5-O-glucuronide and IQ-5-sulfate, as compared with plasma from the negative control group at this time. In contrast, plasma from animals on the NSP-containing wheat straw diet (and to a lesser extent the apple pectin diet) showed significantly lower levels of intact IQ, and significantly higher levels of the two major metabolites, as compared with those from the control rats. These different metabolite profiles were also reflected in different urinary excretion profiles. Urine from rats pre-fed RS-containing diets revealed significantly slower metabolite excretion as compared with urine from rats that had been given the NSP-containing diets. Western blotting methodologies also profiled differences between the effects of these two types of dietary fibre in the expression of xenobiotic metabolizing enzymes. We conclude that changes in activity and expression of xenobiotic metabolising enzymes could play a role in the contrasting effects of these two types of dietary fibre on carcinogen uptake and disposition.

Relationship Between Urinary Nitrate Excretion and Blood Pressure in the InChianti Cohort.

PubMed

Smallwood, Miranda J; Ble, Alessandro; Melzer, David; Winyard, Paul G; Benjamin, Nigel; Shore, Angela C; Gilchrist, Mark

2017-07-01

Inorganic nitrate from the oxidation of endogenously synthesized nitric oxide (NO) or consumed in the diet can be reduced to NO via a complex enterosalivary circulation pathway. The relationship between total nitrate exposure by measured urinary nitrate excretion and blood pressure in a large population sample has not been assessed previously. For this cross-sectional study, 24-hour urinary nitrate excretion was measured by spectrophotometry in the 919 participants from the InChianti cohort at baseline and blood pressure measured with a mercury sphygmomanometer. After adjusting for age and sex only, diastolic blood pressure was 1.9 mm Hg lower in subjects with ≥2 mmol urinary nitrate excretion compared with those excreting <1 mmol nitrate in 24 hours: systolic blood pressure was 3.4 mm Hg (95% confidence interval (CI): -3.5 to -0.4) lower in subjects for the same comparison. Effect sizes in fully adjusted models (for age, sex, potassium intake, use of antihypertensive medications, diabetes, HS-CRP, or current smoking status) were marginally larger: systolic blood pressure in the ≥2 mmol urinary nitrate excretion group was 3.9 (CI: -7.1 to -0.7) mm Hg lower than in the comparison <1 mmol excretion group. Modest differences in total nitrate exposure are associated with lower blood pressure. These differences are at least equivalent to those seen from substantial (100 mmol) reductions in sodium intake. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Exploring the Role of Different Neonatal Nutrition Regimens during the First Week of Life by Urinary GC-MS Metabolomics

PubMed Central

Dessì, Angelica; Murgia, Antonio; Agostino, Rocco; Pattumelli, Maria Grazia; Schirru, Andrea; Scano, Paola; Fanos, Vassilios; Caboni, Pierluigi

2016-01-01

In this study, a gas-chromatography mass spectrometry (GC-MS) metabolomics study was applied to examine urine metabolite profiles of different classes of neonates under different nutrition regimens. The study population included 35 neonates, exclusively either breastfed or formula milk fed, in a seven-day timeframe. Urine samples were collected from intrauterine growth restriction (IUGR), large for gestational age (LGA), and appropriate gestational age (AGA) neonates. At birth, IUGR and LGA neonates showed similarities in their urine metabolite profiles that differed from AGA. When neonates started milk feeding, their metabolite excretion profile was strongly characterized by the different diet regimens. After three days of formula milk nutrition, urine had higher levels of glucose, galactose, glycine and myo-inositol, while up-regulated aconitic acid, aminomalonic acid and adipic acid were found in breast milk fed neonates. At seven days, neonates fed with formula milk shared higher levels of pseudouridine with IUGR and LGA at birth. Breastfed neonates shared up-regulated pyroglutamic acid, citric acid, and homoserine, with AGA at birth. The role of most important metabolites is herein discussed. PMID:26907266

Behavior of heavy metals in human urine and blood following calcium disodium ethylenediamine tetraacetate injection: observations in metal workers.

PubMed

Sata, F; Araki, S; Murata, K; Aono, H

1998-06-12

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the "circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.

Self-monitoring urinary salt excretion in adults: A novel education program for restricting dietary salt intake

PubMed Central

YASUTAKE, KENICHIRO; SAWANO, KAYOKO; YAMAGUCHI, SHOKO; SAKAI, HIROKO; AMADERA, HATSUMI; TSUCHIHASHI, TAKUYA

2011-01-01

This study aimed to examine the usefulness of the self-monitoring of urinary salt excretion for educating individuals about the risk of excessive dietary salt intake. The subjects were 30 volunteers (15 men and 15 women) not consuming anti-hypertensive medication. The subjects measured urinary salt excretion at home for 4 weeks using a self-monitoring device. Blood pressure (BP), anthropometric variables and nutritional variables (by a dietary-habits questionnaire) were measured before and after the measurement of urinary salt excretion. Statistical analyses were performed, including paired t-tests, Chi-square test, Pearson’s product moment correlation coefficient and multiple linear regression analysis. In all subjects, the average urinary salt excretion over 4 weeks was 8.05±1.61 g/day and the range (maximum-minimum value) was 5.58±2.15 g/day. Salt excretion decreased significantly in weeks 3 and 4 (P<0.05 and P<0.01, respectively). Diastolic BP decreased from 77.7±14.3 (at baseline) to 74.3±13.3 after 4 weeks (P<0.05), while systolic BP and anthropometric variables remained unchanged. Nutrition surveys indicated that energy intake was correlated with salt intake both before and after the measurements; changes in both variables during the observation period were correlated (r=0.40, P<0.05). The percentage of subjects who were aware of the restriction in dietary salt intake increased from 47 to 90%. In conclusion, daily monitoring of the amount of urinary salt excretion using a self-monitoring device appears to be an effective educational tool for improving the quality of life of healthy adults. PMID:22977549

Self-monitoring urinary salt excretion in adults: A novel education program for restricting dietary salt intake.

PubMed

Yasutake, Kenichiro; Sawano, Kayoko; Yamaguchi, Shoko; Sakai, Hiroko; Amadera, Hatsumi; Tsuchihashi, Takuya

2011-07-01

This study aimed to examine the usefulness of the self-monitoring of urinary salt excretion for educating individuals about the risk of excessive dietary salt intake. The subjects were 30 volunteers (15 men and 15 women) not consuming anti-hypertensive medication. The subjects measured urinary salt excretion at home for 4 weeks using a self-monitoring device. Blood pressure (BP), anthropometric variables and nutritional variables (by a dietary-habits questionnaire) were measured before and after the measurement of urinary salt excretion. Statistical analyses were performed, including paired t-tests, Chi-square test, Pearson's product moment correlation coefficient and multiple linear regression analysis. In all subjects, the average urinary salt excretion over 4 weeks was 8.05±1.61 g/day and the range (maximum-minimum value) was 5.58±2.15 g/day. Salt excretion decreased significantly in weeks 3 and 4 (P<0.05 and P<0.01, respectively). Diastolic BP decreased from 77.7±14.3 (at baseline) to 74.3±13.3 after 4 weeks (P<0.05), while systolic BP and anthropometric variables remained unchanged. Nutrition surveys indicated that energy intake was correlated with salt intake both before and after the measurements; changes in both variables during the observation period were correlated (r=0.40, P<0.05). The percentage of subjects who were aware of the restriction in dietary salt intake increased from 47 to 90%. In conclusion, daily monitoring of the amount of urinary salt excretion using a self-monitoring device appears to be an effective educational tool for improving the quality of life of healthy adults.

Renal Outcomes and Dietary Potassium: The Overshadowed Electrolyte?

PubMed Central

Jablonski, Kristen L.; Kendrick, Jessica

2014-01-01

Smyth et al. examined the association between urinary sodium and potassium excretion and adverse renal outcomes in adults at high cardiovascular risk. They found no association between urinary sodium excretion and adverse renal outcomes, but a reduced odds of adverse renal outcomes with higher urinary potassium excretion. This finding is quite interesting and a major advancement from this study. It will be important to ascertain whether this finding holds true in individuals free from vascular disease and diabetes, as well as in patients with chronic kidney disease. PMID:25427082

Human urine and plasma concentrations of bisphenol A extrapolated from pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and semi-physiological pharmacokinetic modeling.

PubMed

Miyaguchi, Takamori; Suemizu, Hiroshi; Shimizu, Makiko; Shida, Satomi; Nishiyama, Sayako; Takano, Ryohji; Murayama, Norie; Yamazaki, Hiroshi

2015-06-01

The aim of this study was to extrapolate to humans the pharmacokinetics of estrogen analog bisphenol A determined in chimeric mice transplanted with human hepatocytes. Higher plasma concentrations and urinary excretions of bisphenol A glucuronide (a primary metabolite of bisphenol A) were observed in chimeric mice than in control mice after oral administrations, presumably because of enterohepatic circulation of bisphenol A glucuronide in control mice. Bisphenol A glucuronidation was faster in mouse liver microsomes than in human liver microsomes. These findings suggest a predominantly urinary excretion route of bisphenol A glucuronide in chimeric mice with humanized liver. Reported human plasma and urine data for bisphenol A glucuronide after single oral administration of 0.1mg/kg bisphenol A were reasonably estimated using the current semi-physiological pharmacokinetic model extrapolated from humanized mice data using algometric scaling. The reported geometric mean urinary bisphenol A concentration in the U.S. population of 2.64μg/L underwent reverse dosimetry modeling with the current human semi-physiological pharmacokinetic model. This yielded an estimated exposure of 0.024μg/kg/day, which was less than the daily tolerable intake of bisphenol A (50μg/kg/day), implying little risk to humans. Semi-physiological pharmacokinetic modeling will likely prove useful for determining the species-dependent toxicological risk of bisphenol A. Copyright © 2015 Elsevier Inc. All rights reserved.

Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection. Congenital CMV Longitudinal Study Group.

PubMed

Noyola, D E; Demmler, G J; Williamson, W D; Griesser, C; Sellers, S; Llorente, A; Littman, T; Williams, S; Jarrett, L; Yow, M D

2000-06-01

Cytomegalovirus (CMV) is the most frequent cause of congenital infection, and both symptomatic and asymptomatic infants may have long term sequelae. Children with congenital CMV infection are chronically infected and excrete CMV in the urine for prolonged periods. However, the effect of prolonged viral replication on the long term outcome of these children is unknown. To determine whether duration of CMV excretion is associated with outcome at 6 years of life in symptomatic and asymptomatic congenitally infected children. Longitudinal cohort study. Children congenitally infected with CMV were identified at birth and followed prospectively in a study of long term effects of congenital CMV infection. The relationship between duration of CMV urinary excretion and growth, neurodevelopment and presence and progression of sensorineural hearing loss (SNHL) at 6 years of age was determined. There was no significant difference in the duration of viral urinary excretion between children born with asymptomatic (median, 4.55 years) and symptomatic (median, 2.97 years) congenital CMV infection (P = 0.11). Furthermore there was no association between long term growth or cognitive outcome and duration of viral excretion. However, a significantly greater proportion of children who excreted CMV for <4 years had SNHL and progressive SNHL compared with children with CMV excretion >4 years (P = 0.019, P = 0.009, respectively). Children congenitally infected with CMV are chronically infected for years, but the duration of CMV urinary excretion is not associated with abnormalities of growth, or neurodevelopmental deficits. However, SNHL and progressive SNHL were associated with a shorter duration of CMV excretion.

HPLC method for urinary theobromine determination: Effect of consumption of cocoa products on theobromine urinary excretion in children.

PubMed

Rodriguez, Adrian; Costa-Bauza, Antonia; Saez-Torres, Concepcion; Rodrigo, Dolores; Grases, Felix

2015-11-01

To validate a simple method of urinary theobromine determination, to assess urinary theobromine levels in 80 healthy children and to relate these levels to consumption of cocoa products. Urine samples were diluted, directly injected into an HPLC system, separated by gradient elution on a C18 column, and detected by UV spectrometry. The method was validated for linearity, limits of detection and quantification, imprecision, accuracy, recovery and interferences. The proposed method was used to assess 12-h day and 12-h night urinary theobromine excretion by 80 healthy children, divided into four groups based on consumption of cocoa products. In addition, urinary excretion of magnesium and oxalate, also present in cocoa, was measured in these four groups. The method was linear to a theobromine concentration of 278μmol/L (50mg/L). LOD and LOQ for urine samples, diluted 1:5 (vol/vol) with water, were 1.1 and 3.6μmol/L respectively. Within-run and between-run imprecisions (CV) were each <2%. Average recovery was 99%, and analysis of a certified reference sample showed an error <2.5%. Theobromine excretion levels were significantly higher in healthy children with higher consumption of cocoa products (p<0.001), but oxalate (p=0.098) and magnesium (p=0.068) excretion levels did not differ significantly. This validated method resulted in urinary theobromine determination with 100% recovery, without sample pretreatment. Urinary theobromine levels in healthy children were directly related to their consumption of cocoa products. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended Release Tablet Formulation Using Urinary Pharmacokinetic Data.

PubMed

Mittapalli, Rajendar K; Marroum, Patrick; Qiu, Yihong; Apfelbaum, Kathleen; Xiong, Hao

2017-07-01

To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations. Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability. With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (A e0-24h ) and maximum urinary excretion rate (R max ) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%. A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population.

PubMed

Forni Ogna, Valentina; Ogna, Adam; Vuistiner, Philippe; Pruijm, Menno; Ponte, Belen; Ackermann, Daniel; Gabutti, Luca; Vakilzadeh, Nima; Mohaupt, Markus; Martin, Pierre-Yves; Guessous, Idris; Péchère-Bertschi, Antoinette; Paccaud, Fred; Bochud, Murielle; Burnier, Michel

2015-02-27

Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

The fate of benzoic acid in various species

PubMed Central

Bridges, J. W.; French, M. R.; Smith, R. L.; Williams, R. T.

1970-01-01

1. The urinary excretion of orally administered [14C]benzoic acid in man and 20 other species of animal was examined. 2. At a dose of 50mg/kg, benzoic acid was excreted by the rodents (rat, mouse, guinea pig, golden hamster, steppe lemming and gerbil), the rabbit, the cat and the capuchin monkey almost entirely as hippuric acid (95–100% of 24h excretion). 3. In man at a dose of 1mg/kg and the rhesus monkey at 20mg/kg benzoic acid was excreted entirely as hippuric acid. 4. At 50mg/kg benzoic acid was excreted as hippuric acid to the extent of about 80% of the 24h excretion in the squirrel monkey, pig, dog, ferret, hedgehog and pigeon, the other 20% being found as benzoyl glucuronide and benzoic acid, the latter possibly arising by decomposition of the former. 5. On increasing the dose of benzoic acid to 200mg/kg in the ferret, the proportion of benzoyl glucuronide excreted increased and that of hippuric acid decreased. This did not occur in the rabbit, which excreted 200mg/kg almost entirely as hippuric acid. It appears that the hedgehog and ferret are like the dog in respect to their metabolism of benzoic acid. 6. The Indian fruit bat produced only traces of hippuric acid and possibly has a defect in the glycine conjugation of benzoic acid. The main metabolite in this animal (dose 50mg/kg) was benzoyl glucuronide. 7. The chicken, side-necked turtle and gecko converted benzoic acid mainly into ornithuric acid, but all three species also excreted smaller amounts of hippuric acid. PMID:4990586

Intercalated cell-specific Rh B glycoprotein deletion diminishes renal ammonia excretion response to hypokalemia

PubMed Central

Bishop, Jesse M.; Lee, Hyun-Wook; Handlogten, Mary E.; Han, Ki-Hwan; Verlander, Jill W.

2013-01-01

The ammonia transporter family member, Rh B Glycoprotein (Rhbg), is an ammonia-specific transporter heavily expressed in the kidney and is necessary for the normal increase in ammonia excretion in response to metabolic acidosis. Hypokalemia is a common clinical condition in which there is increased renal ammonia excretion despite the absence of metabolic acidosis. The purpose of this study was to examine Rhbg's role in this response through the use of mice with intercalated cell-specific Rhbg deletion (IC-Rhbg-KO). Hypokalemia induced by feeding a K+-free diet increased urinary ammonia excretion significantly. In mice with intact Rhbg expression, hypokalemia increased Rhbg protein expression in intercalated cells in the cortical collecting duct (CCD) and in the outer medullary collecting duct (OMCD). Deletion of Rhbg from intercalated cells inhibited hypokalemia-induced changes in urinary total ammonia excretion significantly and completely prevented hypokalemia-induced increases in urinary ammonia concentration, but did not alter urinary pH. We conclude that hypokalemia increases Rhbg expression in intercalated cells in the cortex and outer medulla and that intercalated cell Rhbg expression is necessary for the normal increase in renal ammonia excretion in response to hypokalemia. PMID:23220726

Urinary excretion ratio of xanthurenic acid/kynurenic acid as a functional biomarker of niacin nutritional status.

PubMed

Shibata, Katsumi; Yamazaki, Marika; Matsuyama, Yukiyo

2016-07-18

The present study was conducted to survey functional biomarkers for evaluation of niacin nutritional status. Over 500 enzymes require niacin as a coenzyme. Of these, we chose the tryptophan degradation pathway. To create niacin-deficient animals, quinolinic acid phosphoribosyltransferase-knock out mice were used in the present study because wild type mice can synthesize nicotinamide from tryptophan. When the mice were made niacin-deficient, the urinary excretion of xanthurenic acid (XA) was extremely low compared with control mice; however, it increased according to the recovery of niacin nutritional status. The urinary excretion of kynurenic acid (KA) was the reverse of XA. Kynurenine 3-monooxygenase, which needs NADPH, was thought to be suppressed by niacin deficiency. Thus, we calculated the urinary excretion ratio of XA:KA as a functional biomarker of niacin nutrition. The ratio increased according to recovering niacin nutritional status. Low values equate with low niacin nutritional status.

Effect of vitamin A supplementation on the urinary retinol excretion in very low birth weight infants.

PubMed

Schmiedchen, Bettina; Longardt, Ann Carolin; Loui, Andrea; Bührer, Christoph; Raila, Jens; Schweigert, Florian J

2016-03-01

Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570). High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.

Urinary D-lactate excretion in infants receiving Lactobacillus johnsonii with formula.

PubMed

Haschke-Becher, Elisabeth; Brunser, Oscar; Cruchet, Sylvia; Gotteland, Martin; Haschke, Ferdinand; Bachmann, Claude

2008-01-01

Supplementation with certain probiotics can improve gut microbial flora and immune function but should not have adverse effects. This study aimed to assess the risk of D-lactate accumulation and subsequent metabolic acidosis in infants fed on formula containing Lactobacillus johnsonii (La1). In the framework of a double-blind, randomized controlled trial enrolling 71 infants aged 4-5 months, morning urine samples were collected before and 4 weeks after being fed formulas with or without La1 (1 x 10(8)/g powder) or being breastfed. Urinary D- and L-lactate concentrations were assayed by enzymatic, fluorimetric methods and excretion was normalized per mol creatinine. At baseline, no significant differences in urinary D-/L-lactate excretion among the formula-fed and breastfed groups were found. After 4 weeks, D-lactate excretion did not differ between the two formula groups, but was higher in both formula groups than in breastfed infants. In all infants receiving La1, urinary D-lactate concentrations remained within the concentration ranges of age-matched healthy infants which had been determined in an earlier study using the same analytical method. Urinary L-lactate also did not vary over time or among groups. Supplementation of La1 to formula did not affect urinary lactate excretion and there is no evidence of an increased risk of lactic acidosis. Copyright 2008 S. Karger AG, Basel.

Association Between Urinary Sodium and Potassium Excretion and Blood Pressure Among Adults in the United States: National Health and Nutrition Examination Survey, 2014.

PubMed

Jackson, Sandra L; Cogswell, Mary E; Zhao, Lixia; Terry, Ana L; Wang, Chia-Yih; Wright, Jacqueline; Coleman King, Sallyann M; Bowman, Barbara; Chen, Te-Ching; Merritt, Robert; Loria, Catherine M

2018-01-16

Higher levels of sodium and lower levels of potassium intake are associated with higher blood pressure. However, the shape and magnitude of these associations can vary by study participant characteristics or intake assessment method. Twenty-four-hour urinary excretion of sodium and potassium are unaffected by recall errors and represent all sources of intake, and were collected for the first time in a nationally representative US survey. Our objective was to assess the associations of blood pressure and hypertension with 24-hour urinary excretion of sodium and potassium among US adults. Cross-sectional data were obtained from 766 participants age 20 to 69 years with complete blood pressure and 24-hour urine collections in the 2014 National Health and Nutrition Examination Survey, a nationally representative survey of the US noninstitutionalized population. Usual 24-hour urinary electrolyte excretion (sodium, potassium, and their ratio) was estimated from ≤2 collections on nonconsecutive days, adjusting for day-to-day variability in excretion. Outcomes included systolic and diastolic blood pressure from the average of 3 measures and hypertension status, based on average blood pressure ≥140/90 and antihypertensive medication use. After multivariable adjustment, each 1000-mg difference in usual 24-hour sodium excretion was directly associated with systolic (4.58 mm Hg; 95% confidence interval [CI], 2.64-6.51) and diastolic (2.25 mm Hg; 95% CI, 0.83-3.67) blood pressures. Each 1000-mg difference in potassium excretion was inversely associated with systolic blood pressure (-3.72 mm Hg; 95% CI, -6.01 to -1.42). Each 0.5 U difference in sodium-to-potassium ratio was directly associated with systolic blood pressure (1.72 mm Hg; 95% CI, 0.76-2.68). Hypertension was linearly associated with progressively higher sodium and lower potassium excretion; in comparison with the lowest quartile of excretion, the adjusted odds of hypertension for the highest quartile was 4.22 (95% CI, 1.36-13.15) for sodium, and 0.38 (95% CI, 0.17-0.87) for potassium ( P <0.01 for trends). These cross-sectional results show a strong dose-response association between urinary sodium excretion and blood pressure, and an inverse association between urinary potassium excretion and blood pressure, in a nationally representative sample of US adults. © 2017 American Heart Association, Inc.

Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients.

PubMed

Hartmann, Stefan N; Rordorf, Christiane M; Milosavljev, Slavica; Branson, Janice M; Chales, Gérard H; Juvin, Robert R; Lafforgue, Pierre; Le Parc, Jean Marie; Tavernier, Christian G; Meyer, Olivier C

2004-10-01

Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA). To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA. This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment). Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated. Lumiracoxib had no significant effect on the pharmacokinetics, protein binding, or urinary excretion of coadministered methotrexate in patients with RA.

NMR-based urinary profiling of lactulose/mannitol ratio used to assess the altered intestinal permeability in acute on chronic liver failure (ACLF) patients.

PubMed

Kumar, Dinesh; Pandey, Gaurav; Bansal, Deepak; Rawat, Atul; Kumar, Umesh; Dubey, Durgesh; Guleria, Anupam; Saraswat, Vivek Anand

2017-04-01

The article presents a simplified NMR-based protocol for urinary profiling of lactulose/mannitol ratio (LMR) and demonstrates here its utility to assess increased intestinal permeability (IP) in patients with acute on chronic liver failure (ACLF). ACLF is a serious clinical complication associated with chronic liver disease (cirrhosis). The major risk factor in its development is increased IP ('leaky gut'), which has been linked to disease progression and to infectious complications. However, IP has seldom been investigated in patients with ACLF, even though patients frequently report gastrointestinal disorders and associated complications. To this end, we first optimized the NMR-based targeted profiling of urinary metabolites (i.e. actulose, mannitol, and creatinine) and subsequently used this resulted protocol (a) first to evaluate the altered IP in ACLF patients and then (b) to explore its utility for monitoring the treatment response in these patients. The normal profiles were obtained for 7 age and sex matched healthy volunteers. The results revealed that the urinary LMR excretion was significantly higher in ACLF patients compared to normal controls (median ~0.7, range (0.12-2.84), vs median ~0.11, range (0.02-0.28), p < 0.001) suggesting that the ACLF patients' exhibit altered IP. However, the LMR excretion in six clinically improved follow-up ACLF patients was comparable to normal controls indicating restored IP after the treatment. The protocol-as demonstrated here with ACLF-is equally applicable for evaluating IP or mucosal barrier function in other intestinal disorders with reasonable sensitivity and specificity, highlighting its general utility. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Metabolic alkalosis during immobilization in monkeys (M. nemestrina)

NASA Technical Reports Server (NTRS)

Young, D. R.; Yeh, I.; Swenson, R. S.

1983-01-01

The systemic and renal acid-base response of monkeys during ten weeks of immobilization was studied. By three weeks of immobilization, arterial pH and bicarbonate concentrations were elevated (chronic metabolic alkalosis). Net urinary acid excretion increased in immobilized animals. Urinary bicarbonate excretion decreased during the first three weeks of immobilization, and then returned to control levels. Sustained increases in urinary ammonium excretion were seen throughout the time duration of immobilization. Neither potassium depletion nor hypokalemia was observed. Most parameters returned promptly to the normal range during the first week of recovery. Factors tentatively associated with changes in acid-base status of monkeys include contraction of extracellular fluid volume, retention of bicarbonate, increased acid excretion, and possible participation of extrarenal buffers.

Fish Oil Supplementation and Urinary Oxalate Excretion in Normal Subjects on a Low-oxalate Diet

PubMed Central

Lange, Jessica N.; Mufarrij, Patrick W.; Easter, Linda; Knight, John; Holmes, Ross P.; Assimos, Dean G.

2014-01-01

OBJECTIVE To determine if fish oil supplementation reduces endogenous oxalate synthesis in healthy subjects. MATERIALS AND METHODS Fifteen healthy non–stone-forming adults participated in this study. Subjects first abstained from using vitamins, medications, or foods enriched in omega-3 fatty acids for 30 days. Next, they collected two 24-hour urine specimens while consuming a self-selected diet. Subjects consumed an extremely low-oxalate and normal-calcium diet for 5 days and collected 24-hour urine specimens on the last 3 days of this diet. Next, the subjects took 2 fish oil capsules containing 650-mg eicosapentaenoic acid and 450-mg docosahexaenoic acid twice daily for 30 days. They consumed a self-selected diet on days 1–25 and the controlled diet on days 26–30. Twenty-four-hour urine samples were collected on days 28–30. Excretion levels of urinary analytes including oxalate and glycolate were analyzed. RESULTS Although there was a significant reduction in urinary oxalate, magnesium, and potassium excretions and an increase in uric acid excretion during the controlled dietary phases compared with the self-selected diet, there were no significant differences in their excretion during controlled diet phases with and without fish oil supplementation. CONCLUSION These results suggest that fish oil supplementation does not reduce endogenous oxalate synthesis or urinary oxalate excretion in normal adults during periods of extremely low oxalate intake. However, these results do not challenge the previously described reduction in urinary oxalate excretion demonstrated in normal subjects consuming a moderate amount of oxalate in conjunction with fish oil. PMID:25102784

Lack of enzyme induction with oxcarbazepine (600 mg daily) in healthy subjects.

PubMed Central

Larkin, J G; McKee, P J; Forrest, G; Beastall, G H; Park, B K; Lowrie, J I; Lloyd, P; Brodie, M J

1991-01-01

1. Oxcarbazepine (OXC), the 10-keto analogue of carbamazepine (CBZ), has similar anticonvulsant efficacy and possibly improved patient tolerability. Unlike CBZ, it is metabolised by reduction and may not induce hepatic monooxygenase enzymes. 2. Serum concentrations of OXC and its active metabolite 10-OH-carbazepine (10-OH-CZ) were followed after a single 300 mg dose and during and after 300 mg OXC twice daily for 29 doses in eight healthy male volunteers. 3. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, sex hormone binding globulin (SHBG) levels and circulating androgens were measured as indices of hepatic enzyme induction before, during and after treatment with OXC. 4. Elimination half-lives (mean +/- s.e. mean) of 10-OH-CZ were unaltered by 2 weeks' therapy with OXC (before 11.3 +/- 1.1 h; after 13.9 +/- 3 h). Trough plasma concentrations of 10-OH-CZ at steady-state (31 +/- 2.2 mumol l-1) were higher than predicted (16.5 +/- 4 mumol l-1). 5. Antipyrine metabolism, urinary 6-beta-hydroxycortisol excretion, SHBG levels and circulating androgens were unaltered by treatment with OXC. 6. OXC (600 mg daily) does not induce hepatic monooxygenase enzymes and so is likely to have more predictable dose-concentration relationships and to produce fewer physiological and pharmacological interactions than CBZ. PMID:2015172

Physiologicomathematical model for studying human exposure to organic solvents: kinetics of blood/tissue n-hexane concentrations and of 2,5-hexanedione in urine.

PubMed Central

Perbellini, L; Mozzo, P; Brugnone, F; Zedde, A

1986-01-01

The physiologicomathematical model with eight compartments described allows the simulation of the absorbtion, distribution, biotransformation, excretion of an organic solvent, and the kinetics of its metabolites. The usual compartments of the human organism (vessel rich group, muscle group, and fat group) are integrated with the lungs, the metabolising tissues, and three other compartments dealing with the metabolic kinetics (biotransformation, water, and urinary compartments). The findings obtained by mathematical simulation of exposure to n-hexane were compared with data previously reported. The concentrations of n-hexane in alveolar air and in venous blood described both in experimental and occupational exposures provided a substantial validation for the data obtained by mathematical simulation. The results of the urinary excretion of 2,5-hexanedione given by the model were in good agreement with data already reported. The simulation of an exposure to n-hexane repeated five days a week suggested that the solvent accumulates in the fat tissue. The half life of n-hexane in fat tissue equalled 64 hours. The kinetics of 2,5-hexanedione resulting from the model suggest that occupational exposure results in the presence of large amounts of 2,5-hexanedione in the body for the whole working week. PMID:3790456

Physiologically-Based Toxicokinetic Modeling of Zearalenone and Its Metabolites: Application to the Jersey Girl Study

PubMed Central

Mukherjee, Dwaipayan; Royce, Steven G.; Alexander, Jocelyn A.; Buckley, Brian; Isukapalli, Sastry S.; Bandera, Elisa V.; Zarbl, Helmut; Georgopoulos, Panos G.

2014-01-01

Zearalenone (ZEA), a fungal mycotoxin, and its metabolite zeranol (ZAL) are known estrogen agonists in mammals, and are found as contaminants in food. Zeranol, which is more potent than ZEA and comparable in potency to estradiol, is also added as a growth additive in beef in the US and Canada. This article presents the development and application of a Physiologically-Based Toxicokinetic (PBTK) model for ZEA and ZAL and their primary metabolites, zearalenol, zearalanone, and their conjugated glucuronides, for rats and for human subjects. The PBTK modeling study explicitly simulates critical metabolic pathways in the gastrointestinal and hepatic systems. Metabolic events such as dehydrogenation and glucuronidation of the chemicals, which have direct effects on the accumulation and elimination of the toxic compounds, have been quantified. The PBTK model considers urinary and fecal excretion and biliary recirculation and compares the predicted biomarkers of blood, urinary and fecal concentrations with published in vivo measurements in rats and human subjects. Additionally, the toxicokinetic model has been coupled with a novel probabilistic dietary exposure model and applied to the Jersey Girl Study (JGS), which involved measurement of mycoestrogens as urinary biomarkers, in a cohort of young girls in New Jersey, USA. A probabilistic exposure characterization for the study population has been conducted and the predicted urinary concentrations have been compared to measurements considering inter-individual physiological and dietary variability. The in vivo measurements from the JGS fall within the high and low predicted distributions of biomarker values corresponding to dietary exposure estimates calculated by the probabilistic modeling system. The work described here is the first of its kind to present a comprehensive framework developing estimates of potential exposures to mycotoxins and linking them with biologically relevant doses and biomarker measurements, including a systematic characterization of uncertainties in exposure and dose estimation for a vulnerable population. PMID:25474635

Assessment of urinary betaine as a marker of diabetes mellitus in cardiovascular patients.

PubMed

Schartum-Hansen, Hall; Ueland, Per M; Pedersen, Eva R; Meyer, Klaus; Ebbing, Marta; Bleie, Øyvind; Svingen, Gard F T; Seifert, Reinhard; Vikse, Bjørn E; Nygård, Ottar

2013-01-01

Abnormal urinary excretion of betaine has been demonstrated in patients with diabetes or metabolic syndrome. We aimed to identify the main predictors of excretion in cardiovascular patients and to make initial assessment of its feasibility as a risk marker of future diabetes development. We used data from 2396 patients participating in the Western Norway B-vitamin Intervention Trial, who delivered urine and blood samples at baseline, and in the majority at two visits during follow-up of median 39 months. Betaine in urine and plasma were measured by liquid-chromatography-tandem mass spectrometry. The strongest determinants of urinary betaine excretion by multiple regression were diabetes mellitus, age and estimated glomerular filtration rate; all p<0.001. Patients with diabetes mellitus (n = 264) had a median excretion more than three times higher than those without. We found a distinct non-linear association between urinary betaine excretion and glycated hemoglobin, with a break-point at 6.5%, and glycated hemoglobin was the strongest determinant of betaine excretion in patients with diabetes mellitus. The discriminatory power for diabetes mellitus corresponded to an area under the curve by receiver-operating characteristics of 0.82, and betaine excretion had a coefficient of reliability of 0.73. We also found a significant, independent log-linear relation between baseline betaine excretion and the risk of developing new diabetes during follow-up. The good discriminatory power for diabetes, high test-retest stability and independent association with future risk of new diabetes should motivate further investigation on the role of betaine excretion in risk assessment and long-term follow-up of diabetes mellitus.

Measurement of Menadione in Urine by HPLC

PubMed Central

Rajabi, Ala Al; Peterson, James; Choi, Sang Woon; Suttie, John; Barakat, Susan; Booth, Sarah L

2010-01-01

Menadione is a metabolite of vitamin K that is excreted in urine. A high performance liquid chromatography (HPLC) method using a C30 column, post-column zinc reduction and fluorescence detection was developed to measure urinary menadione. The mobile phase was composed of 95% methanol with 0.55% aqueous solution and 5% DI H2O. Menaquinone-2 (MK-2) was used as an internal standard. The standard calibration curve was linear with a correlation coefficient (R2) of 0.999 for both menadione and MK-2. The lower limit of quantification (LLOQ) was 0.3 pmole menadione/mL urine. Sample preparation involved hydrolysis of menadiol conjugates and oxidizing the released menadiol to menadione. Using this method, urinary menadione was shown to increase in response to 3 years of phylloquinone supplementation. This HPLC method is a sensitive and reproducible way to detect menadione in urine. Research support: USDA ARS Cooperative Agreement 58-1950-7-707. PMID:20719580

Measurement of menadione in urine by HPLC.

PubMed

Al Rajabi, Ala; Peterson, James; Choi, Sang-Woon; Suttie, John; Barakat, Susan; Booth, Sarah L

2010-09-15

Menadione is a metabolite of vitamin K that is excreted in urine. A high performance liquid chromatography (HPLC) method using a C(30) column, post-column zinc reduction and fluorescence detection was developed to measure urinary menadione. The mobile phase was composed of 95% methanol with 0.55% aqueous solution and 5% DI H(2)O. Menaquinone-2 (MK-2) was used as an internal standard. The standard calibration curve was linear with a correlation coefficient (R(2)) of 0.999 for both menadione and MK-2. The lower limit of quantification (LLOQ) was 0.3pmole menadione/mL urine. Sample preparation involved hydrolysis of menadiol conjugates and oxidizing the released menadiol to menadione. Using this method, urinary menadione was shown to increase in response to 3 years of phylloquinone supplementation. This HPLC method is a sensitive and reproducible way to detect menadione in urine. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Desmopressin resistant nocturnal polyuria secondary to increased nocturnal osmotic excretion.

PubMed

Dehoorne, Jo L; Raes, Ann M; van Laecke, Erik; Hoebeke, Piet; Vande Walle, Johan G

2006-08-01

We investigated the role of increased solute excretion in children with desmopressin resistant nocturnal enuresis and nocturnal polyuria. A total of 42 children with monosymptomatic nocturnal enuresis and significant nocturnal polyuria with high nocturnal urinary osmolality (more than 850 mmol/l) were not responding to desmopressin. A 24-hour urinary concentration profile was obtained with measurement of urine volume, osmolality, osmotic excretion and creatinine. The control group consisted of 100 children without enuresis. Based on osmotic excretion patients were classified into 3 groups. Group 1 had 24-hour increased osmotic excretion, most likely secondary to a high renal osmotic load. This was probably diet related since 11 of these 12 patients were obese. Group 2 had increased osmotic excretion in the evening and night, probably due to a high renal osmotic load caused by the diet characteristics of the evening meal. Group 3 had deficient osmotic excretion during the day, secondary to extremely low fluid intake to compensate for small bladder capacity. Nocturnal polyuria with high urinary osmolality in our patients with desmopressin resistant monosymptomatic nocturnal enuresis is related to abnormal increased osmotic excretion. This may be explained by their fluid and diet habits, eg daytime fluid restriction, and high protein and salt intake.

Quantitative determination of five metabolites of aspirin by UHPLC-MS/MS coupled with enzymatic reaction and its application to evaluate the effects of aspirin dosage on the metabolic profile.

PubMed

Li, Jian-Ping; Guo, Jian-Ming; Shang, Er-Xin; Zhu, Zhen-Hua; Liu, Yang; Zhao, Bu-Chang; Zhao, Jing; Tang, Zhi-Shu; Duan, Jin-Ao

2017-05-10

Acetylsalicylic acid (Aspirin, ASA) is a famous drug for cardiovascular diseases in recent years. Effects of ASA dosage on the metabolic profile have not been fully understood. The purpose of our study is to establish a rapid and reliable method to quantify ASA metabolites in biological matrices, especially for glucuronide metabolites whose standards are not commercially available. Then we applied this method to evaluate the effects of ASA dosage on the metabolic and excretion profile of ASA metabolites in rat urine. Salicylic acid (SA), gentisic acid (GA) and salicyluric acid (SUA) were determined directly by UHPLC-MS/MS, while salicyl phenolic glucuronide (SAPG) and salicyluric acid phenolic glucuronide (SUAPG) were quantified indirectly by measuring the released SA and SUA from SAPG and SUAPG after β-glucuronidase digestion. SUA and SUAPG were the major metabolites of ASA in rat urine 24h after ASA administration, which accounted for 50% (SUA) and 26% (SUAPG). When ASA dosage was increased, the contributions dropped to 32% and 18%, respectively. The excretion of other three metabolites (GA, SA and SAPG) however showed remarkable increases by 16%, 6% and 4%, respectively. In addition, SUA and SUAPG were mainly excreted in the time period of 12-24h, while GA was excreted in the earlier time periods (0-4h and 4-8h). SA was mainly excreted in the time period of 0-4h and 12-24h. And the excretion of SAPG was equally distributed in the four time periods. We went further to show that the excretion of five metabolites in rat urine was delayed when ASA dosage was increased. In conclusion, we have developed a rapid and sensitive method to determine the five ASA metabolites (SA, GA, SUA, SAPG and SUAPG) in rat urine. We showed that ASA dosage could significantly influence the metabolic and excretion profile of ASA metabolites in rat urine. Copyright © 2016 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, L.

The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Camore » 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies.« less

Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones.

PubMed

Goldfarb, David S; MacDonald, Patricia A; Gunawardhana, Lhanoo; Chefo, Solomon; McLean, Lachy

2013-11-01

Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation. Febuxostat, a xanthine oxidoreductase inhibitor, is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout. This work studied whether febuxostat, compared with allopurinol and placebo, would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation. In this 6-month, double-blind, multicenter, randomized controlled trial, hyperuricosuric participants with a recent history of calcium stones and one or more radio-opaque calcium stone ≥ 3 mm (as seen by multidetector computed tomography) received daily febuxostat at 80 mg, allopurinol at 300 mg, or placebo. The primary end point was percent change from baseline to month 6 in 24-hour urinary uric acid. Secondary end points included percent change from baseline to month 6 in size of index stone and change from baseline in the mean number of stones and 24-hour creatinine clearance. Of 99 enrolled participants, 86 participants completed the study. Febuxostat led to significantly greater reduction in 24-hour urinary uric acid (-58.6%) than either allopurinol (-36.4%; P=0.003) or placebo (-12.7%; P<0.001). Percent change from baseline in the size of the largest calcium stone was not different with febuxostat compared with allopurinol or placebo. There was no change in stone size, stone number, or renal function. No new safety concerns were noted for either drug. Febuxostat (80 mg) lowered 24-hour urinary uric acid significantly more than allopurinol (300 mg) in stone formers with higher urinary uric acid excretion after 6 months of treatment. There was no change in stone size or number over the 6-month period.

Clinical significance of CYP2C19 polymorphisms on the metabolism and pharmacokinetics of 11β-hydroxysteroid dehydrogenase type-1 inhibitor BMS-823778.

PubMed

Cheng, Yaofeng; Wang, Lifei; Iacono, Lisa; Zhang, Donglu; Chen, Weiqi; Gong, Jiachang; Humphreys, William Griffith; Gan, Jinping

2018-01-01

BMS-823778 is an inhibitor of 11β-hydroxysteroid dehydrogenase type-1, and thus a potential candidate for Type 2 diabetes treatment. Here, we investigated the metabolism and pharmacokinetics of BMS-823778 to understand its pharmacokinetic variations in early clinical trials. The metabolism of BMS-823778 was characterized in multiple in vitro assays. Pharmacokinetics were evaluated in healthy volunteers, prescreened as CYP2C19 extensive metabolizers (EM) or poor metabolizers (PM), with a single oral dose of [ 14 C]BMS-823778 (10 mg, 80 μCi). Three metabolites (<5%) were identified in human hepatocytes and liver microsomes (HLM) incubations, including two hydroxylated metabolites (M1 and M2) and one glucuronide conjugate (M3). As the most abundant metabolite, M1 was formed mainly through CYP2C19. M1 formation was also correlated with CYP2C19 activities in genotyped HLM. In humans, urinary excretion of dosed radioactivity was significantly higher in EM (68.8%; 95% confidence interval 61.3%, 76.3%) than in PM (47.0%; 43.5%, 50.6%); only small portions (<2%) were present in faeces or bile from both genotypes. In plasma, BMS-823778 exposure in PM was significantly (5.3-fold, P = 0.0097) higher than in EM. Furthermore, total radioactivity exposure was significantly higher (P < 0.01) than BMS-823778 exposure in all groups, indicating the presence of metabolites. M1 was the only metabolite observed in plasma, and much lower in PM. In urine, the amount of M1 and its oxidative metabolite in EM was 7-fold of that in PM, while more glucuronide conjugates of BMS-823778 and M1 were excreted in PM. CYP2C19 polymorphisms significantly impacted systemic exposure and metabolism pathways of BMS-823778 in humans. © 2017 The British Pharmacological Society.

Biotransformation of the novel inotropic agent toborinone (OPC-18790) in rats and dogs. Evidence for the formation of novel glutathione and two cysteine conjugates.

PubMed

Kitani, M; Miyamoto, G; Nagasawa, M; Yamada, T; Matsubara, J; Uchida, M; Odomi, M

1997-06-01

The metabolism of toborinone, (+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quin - olinone, a novel inotropic agent, was studied in rats and dogs after intravenous administration. Chemical structures of the 13 metabolites were characterized by direct-probe FAB/MS and field desorption/MS, LC/FAB/MS, and various NMR measurements. After intravenous dosing of 10 mg/kg [14C]toborinone, fecal and urinary recoveries of the 14C dose were approximately 70% and 26-30%, respectively, in both rats and dogs. The predominant component of radioactivity was the unchanged toborinone in every biological specimen in rats and dogs. Although unchanged toborinone was predominantly observed, toborinone underwent extensive conjugations with glucuronic acid, sulfate, and glutathione, either directly or following phase I reaction. Metabolites resulting from oxidative N-C cleavage were minor both in number and in quantity in every biological specimen in rats and dogs. In rats, toborinone underwent O-demethylation to form M-7 and successive phase it reaction to yield the glucuronide M-1 and the sulfoconjugate M-2, and deconjugation to yield M-7, which was a primary metabolite accounted for 35.67% of the radioactivity excreted in the feces by 48 hr. Conjugates M-1 and M-2 were the major metabolites in rat plasma. In dogs, toborinone was metabolized via mercapturic acid pathway to yield the primary metabolites, cysteine conjugates M-10 and M-11 that accounted for 19.10% and 6.70% of the radioactivity excreted in the feces by 48 hr and that were detected species specifically in dogs. The glutathione conjugate M-13, which was isolated from in vitro incubations using dog liver, led us to consider a possible mercapturic acid pathway from the parent compound to M-10. Metabolites in dog plasma and those in urine in both rats and dogs were minor in quantity. The metabolic pathways of toborinone in rats and dogs are proposed herein.

Pharmacokinetics of anthocyanidin-3-glycosides following consumption of Hibiscus sabdariffa L. extract.

PubMed

Frank, Thomas; Janssen, Marlies; Netzel, Michael; Strass, Gabriele; Kler, Adolf; Kriesl, Erwin; Bitsch, Irmgard

2005-02-01

Pharmacokinetic parameters of several dietary anthocyanins following consumption of Hibiscus sabdariffa L. extract were determined in 6 healthy volunteers. Subjects were given a single oral dose of 150 mL of Hibiscus sabdariffa L. extract yielding 62.6 mg of cyanidin-3-sambubioside, 81.6 mg of delphindin-3-sambubioside, and 147.4 mg of total anthocyanins (calculated as cyanidin equivalents). Within 7 hours, the urinary excretion of cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins (ie, the sum of all quantifiable anthocyanidin glycosides) was 0.016%, 0.021%, and 0.018% of the administered doses, respectively. Maximum excretion rates were determined at 1.5 to 2.0 hours after intake. The dose-normalized plasma area under the curve estimates were 0.076, 0.032, and 0.050 ng x h/mL/mg for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The dose-normalized C(max) estimates were 0.036, 0.015, and 0.023 ng/mL/mg in the same sequence. They were reached each at 1.5 hours (median) after intake. The geometric means of t1/2 were 2.18, 3.34, and 2.63 hours for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The urinary excretion of intact anthocyanins was fast and appeared to be monoexponential. To evaluate the contribution of anthocyanins to the health-protecting effects of Hibiscus sabdariffa L. extract, it will be necessary to perform further studies on both the intact glycosides and their in vivo metabolites or conjugates in human plasma and urine.

Creosote bush (Larrea tridentata) resin increases water demands and reduces energy availability in desert woodrats (Neotoma lepida).

PubMed

Mangione, Antonio M; Dearing, M Denise; Karasov, William H

2004-07-01

Although many plant secondary compounds are known to have serious consequences for herbivores, the costs of processing them are generally unknown. Two potential costs of ingestion and detoxification of secondary compounds are elevation of the minimum drinking water requirement and excretion of energetically expensive metabolites (i.e., glucuronides) in the urine. To address these impacts, we studied the costs of ingestion of resin from creosote bush (Larrea tridentata) on desert woodrats (Neotoma lepida). The following hypotheses were tested: ingestion of creosote resin by woodrats (1) increases minimum water requirement and (2) reduces energy available by increasing fecal and urinary energy losses. We tested the first hypothesis, by measuring the minimum water requirement of woodrats fed a control diet with and without creosote resin. Drinking water was given in decreasing amounts until woodrats could no longer maintain constant body mass. In two separate experiments, the minimum drinking water requirement of woodrats fed resin was higher than that of controls by 18-30% (about 1-1.7 ml/d). We tested several potential mechanisms of increased water loss associated with the increase in water requirement. The rate of fecal water loss was higher in woodrats consuming resin. Neither urinary water nor evaporative water loss was affected by ingestion of resin. Hypothesis 2 was tested by measuring energy fluxes of woodrats consuming control vs. resin-treated diets. Woodrats on a resin diet had higher urinary energy losses and, thus, metabolized a lower proportion of the dietary energy than did woodrats on control diet. Fecal energy excretion was not affected by resin. The excretion of glucuronic acid represented almost half of the energy lost as a consequence of resin ingestion. The increased water requirement and energy losses of woodrats consuming a diet with resin could have notable ecological consequences.

Major metabolite of F2-isoprostane in urine may be a more sensitive biomarker of oxidative stress than isoprostane itself1234

PubMed Central

Dorjgochoo, Tsogzolmaa; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-ou; Yang, Gong; Cai, Qiuyin; Rothman, Nathaniel; Cai, Hui; Li, Honglan; Deng, Xinqing; Franke, Adrian; Roberts, L Jackson; Milne, Ginger; Zheng, Wei; Dai, Qi

2012-01-01

Background: There is limited literature on the contributors to isoprostane metabolite 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (15-F2t-IsoP-M) compared with F2-isoprostanes (F2-IsoPs) as an oxidative stress biomarker. Objective: The objective of this study was to investigate whether plasma concentrations of antioxidants, urinary excretion rates of polyphenols, and antioxidants in food and dietary supplements are attributable to both urinary F2-IsoP and 15-F2t-IsoP-M concentrations. Design: Dietary intake information and blood and urine samples were obtained from 845 healthy middle-aged and elderly female participants of the Shanghai Women's Health Study. Urinary isoprostanes (F2-IsoPs and 15-F2t-IsoP-M) were measured and adjusted for creatinine concentrations. Results: Urinary 15-F2t-IsoP-M and F2-IsoP concentrations were lower in subjects who used a multivitamin. Lower F2-IsoP concentrations were observed in ginseng users, whereas lower concentrations of 15-F2t-IsoP-M were shown in subjects who used a vitamin E supplement. Plasma concentrations of several antioxidants (ie, β-carotenes, both trans and cis β-carotenes, lycopene other than trans, 5-cis and 7-cis isomers, cis anhydrolutein, and cis β-cryptoxanthin) were inversely associated with 15-F2t-IsoP-M but not with F2-IsoPs, whereas β-, γ-, and δ-tocopherols were positively associated with 15-F2t-IsoP-M but not with F2-IsoPs. Urinary polyphenol quercetin was positively associated with both F2-IsoPs and 15-F2t-IsoP-M. Conclusion: The results suggest that the F2-IsoP major metabolite 15-F2t-IsoP-M may be a more sensitive marker of endogenous oxidative stress status than are F2-IsoPs in the assessment of effects of antioxidants on age-related diseases. PMID:22760572

Effect of sauna bathing and beer ingestion on plasma concentrations of purine bases.

PubMed

Yamamoto, Tetsuya; Moriwaki, Yuji; Ka, Tuneyoshi; Takahashi, Sumio; Tsutsumi, Zenta; Cheng, Jidong; Inokuchi, Taku; Yamamoto, Asako; Hada, Toshikazu

2004-06-01

To determine whether sauna bathing alone or in combination with beer ingestion increases the plasma concentration of uric acid, 5 healthy subjects were tested. Urine and plasma measurements were performed before and after each took a sauna bath, ingested beer, and ingested beer just after taking a sauna bath, with a 2-week interval between each activity. Sauna bathing alone increased the plasma concentrations of uric acid and oxypurines (hypoxanthine and xanthine), and decreased the urinary and fractional excretion of uric acid, while beer ingestion alone increased the plasma concentrations and urinary excretion of uric acid and oxypurines. A combination of both increased the plasma concentration of uric acid and oxypurines, and decreased the urinary and fractional excretion of uric acid, with an increase in the urinary excretion of oxypurines. The increase in plasma concentration of uric acid with the combination protocol was not synergistic as compared to the sum of the increases by each alone. Body weight, urine volume, and the urinary excretion of sodium and chloride via dehydration were decreased following sauna bathing alone. These results suggest that sauna bathing had a relationship with enhanced purine degradation and a decrease in the urinary excretion of uric acid, leading to an increase in the plasma concentration of uric acid. Further, we concluded that extracellular volume loss may affect the common renal transport pathway of uric acid and xanthine. Therefore, it is recommended that patients with gout refrain from drinking alcoholic beverages, including beer, after taking a sauna bath, since the increase in plasma concentration of uric acid following the combination of sauna bathing and beer ingestion was additive.

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis

PubMed Central

Huh, Ji Hye; Lee, Kyong Joo; Lim, Jung Soo; Lee, Mi Young; Park, Hong Jun; Kim, Moon Young; Kim, Jae Woo; Chung, Choon Hee; Shin, Jang Yel; Kim, Hyun-Soo; Kwon, Sang Ok; Baik, Soon Koo

2015-01-01

Background Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans. Methods We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008–2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka’s equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD. Results The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26–1.55, in HSI; OR 1.75, CI 1.39–2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values. Conclusions High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis. PMID:26571018

Sodium in the Finnish diet: 20-year trends in urinary sodium excretion among the adult population.

PubMed

Laatikainen, T; Pietinen, P; Valsta, L; Sundvall, J; Reinivuo, H; Tuomilehto, J

2006-08-01

High sodium intake increases the risk of cardiovascular diseases and may also be associated with higher rates of stomach cancer, asthma disorders and infections. In Finland, cross-sectional population surveys to monitor cardiovascular risk factors have been carried out since the 1970s. The main aim of this paper is to present trends in urinary sodium and potassium excretion from 1979 to 2002. Cross-sectional population surveys on cardiovascular risk factors. Surveys were carried out in Finland in 1979, 1982, 1987 and 2002 in four geographical areas: North Karelia, the Kuopio area, Southwestern Finland and the Helsinki area. For each survey a random sample stratified by age and sex was drawn from the population register. In this analysis, participants of urine collection subsamples aged 25-64 years (n = 4648) were included. A 24-h urinary collection was carried out in subsamples (n = 2218-2487) in connection with population risk factor surveys. Urinary sodium and potassium concentrations were analyzed in the same laboratory throughout, using a flame photometer in 1979, 1982 and 1987 and an ion-selective electrode in 2002. Between 1979 and 2002 urinary sodium excretion in Finland decreased from over 220 to less than 170 mmol/day among men and from nearly 180 to less than 130 mmol/day among women. Although potassium excretion decreased somewhat as well, the decrease in sodium-potassium molar ratio was also significant. The 24-h urinary sodium excretion in Finland has decreased significantly during the last 20 years. However, excretion levels are still considerably higher than recommendations. A further decrease in sodium intake remains a goal for the Finnish food industry and consumers. All surveys were funded by the National Public Health Institute in Finland.

High Dietary Sodium Intake Assessed by Estimated 24-h Urinary Sodium Excretion Is Associated with NAFLD and Hepatic Fibrosis.

PubMed

Huh, Ji Hye; Lee, Kyong Joo; Lim, Jung Soo; Lee, Mi Young; Park, Hong Jun; Kim, Moon Young; Kim, Jae Woo; Chung, Choon Hee; Shin, Jang Yel; Kim, Hyun-Soo; Kwon, Sang Ok; Baik, Soon Koo

2015-01-01

Although high sodium intake is associated with obesity and hypertension, few studies have investigated the relationship between sodium intake and non-alcoholic fatty liver disease (NAFLD). We evaluated the association between sodium intake assessed by estimated 24-h urinary sodium excretion and NAFLD in healthy Koreans. We analyzed data from 27,433 participants in the Korea National Health and Nutrition Examination Surveys (2008-2010). The total amount of sodium excretion in 24-h urine was estimated using Tanaka's equations from spot urine specimens. Subjects were defined as having NAFLD when they had high scores in previously validated NAFLD prediction models such as the hepatic steatosis index (HSI) and fatty liver index (FLI). BARD scores and FIB-4 were used to define advanced fibrosis in subjects with NAFLD. The participants were classified into three groups according to estimated 24-h urinary excretion tertiles. The prevalence of NAFLD as assessed by both FLI and HSI was significantly higher in the highest estimated 24-h urinary sodium excretion tertile group. Even after adjustment for confounding factors including body fat and hypertension, the association between higher estimated 24-h urinary sodium excretion and NAFLD remained significant (Odds ratios (OR) 1.39, 95% confidence interval (CI) 1.26-1.55, in HSI; OR 1.75, CI 1.39-2.20, in FLI, both P < 0.001). Further, subjects with hepatic fibrosis as assessed by BARD score and FIB-4 in NAFLD patients had higher estimated 24-h urinary sodium values. High sodium intake was independently associated with an increased risk of NAFLD and advanced liver fibrosis.

Polyethylene glycol versus dual sugar assay for gastrointestinal permeability analysis: is it time to choose?

PubMed

van Wijck, Kim; Bessems, Babs Afm; van Eijk, Hans Mh; Buurman, Wim A; Dejong, Cornelis Hc; Lenaerts, Kaatje

2012-01-01

Increased intestinal permeability is an important measure of disease activity and prognosis. Currently, many permeability tests are available and no consensus has been reached as to which test is most suitable. The aim of this study was to compare urinary probe excretion and accuracy of a polyethylene glycol (PEG) assay and dual sugar assay in a double-blinded crossover study to evaluate probe excretion and the accuracy of both tests. Gastrointestinal permeability was measured in nine volunteers using PEG 400, PEG 1500, and PEG 3350 or lactulose-rhamnose. On 4 separate days, permeability was analyzed after oral intake of placebo or indomethacin, a drug known to increase intestinal permeability. Plasma intestinal fatty acid binding protein and calprotectin levels were determined to verify compromised intestinal integrity after indomethacin consumption. Urinary samples were collected at baseline, hourly up to 5 hours after probe intake, and between 5 and 24 hours. Urinary excretion of PEG and sugars was determined using high-pressure liquid chromatography-evaporative light scattering detection and liquid chromatography-mass spectrometry, respectively. Intake of indomethacin increased plasma intestinal fatty acid-binding protein and calprotectin levels, reflecting loss of intestinal integrity and inflammation. In this state of indomethacin-induced gastrointestinal compromise, urinary excretion of the three PEG probes and lactulose increased compared with placebo. Urinary PEG 400 excretion, the PEG 3350/PEG 400 ratio, and the lactulose/rhamnose ratio could accurately detect indomethacin-induced increases in gastrointestinal permeability, especially within 2 hours of probe intake. Hourly urinary excretion and diagnostic accuracy of PEG and sugar probes show high concordance for detection of indomethacin-induced increases in gastrointestinal permeability. This comparative study improves our knowledge of permeability analysis in man by providing a clear overview of both tests and demonstrates equivalent performance in the current setting.

Anemia, Iron Deficiency and Iodine Deficiency among Nepalese School Children.

PubMed

Khatiwada, Saroj; Lamsal, Madhab; Gelal, Basanta; Gautam, Sharad; Nepal, Ashwini Kumar; Brodie, David; Baral, Nirmal

2016-07-01

To assess iodine and iron nutritional status among Nepalese school children. A cross-sectional, community based study was conducted in the two districts, Ilam (hilly region) and Udayapur (plain region) of eastern Nepal. A total of 759 school children aged 6-13 y from different schools within the study areas were randomly enrolled. A total of 759 urine samples and 316 blood samples were collected. Blood hemoglobin level, serum iron, total iron binding capacity and urinary iodine concentration was measured. Percentage of transferrin saturation was calculated using serum iron and total iron binding capacity values. The mean level of hemoglobin, serum iron, total iron binding capacity, transferrin saturation and median urinary iodine excretion were 12.29 ± 1.85 g/dl, 70.45 ± 34.46 μg/dl, 386.48 ± 62.48 μg/dl, 19.94 ± 12.07 % and 274.67 μg/L respectively. Anemia, iron deficiency and iodine deficiency (urinary iodine excretion <100 μg/L) were present in 34.5 %, 43.4 % and 12.6 % children respectively. Insufficient urinary iodine excretion (urinary iodine excretion <100 μg/L) was common in anemic and iron deficient children. Iron deficiency and anemia are common in Nepalese children, whereas, iodine nutrition is more than adequate. Low urinary iodine excretion was common in iron deficiency and anemia.

The salt-taste threshold in untreated hypertensive patients.

PubMed

Kim, Chang-Yeon; Ye, Mi-Kyung; Lee, Young Soo

2017-01-01

The salt-taste threshold can influence the salt appetite, and is thought to be another marker of sodium intake. Many studies have mentioned the relationship between the sodium intake and blood pressure (BP). The aim of this study was to evaluate the relationship between the salt-taste threshold and urinary sodium excretion in normotensive and hypertensive groups. We analyzed 199 patients (mean age 52 years, male 47.3%) who underwent 24-h ambulatory BP monitoring (ABPM). Hypertension was diagnosed as an average daytime systolic BP of ≥135 mmHg or diastolic BP of ≥85 mmHg by the ABPM. We assessed the salt-taste threshold using graded saline solutions. The salt-taste threshold, 24-h urinary sodium and potassium excretion, and echocardiographic data were compared between the control and hypertensive groups. The detection and recognition threshold of the salt taste did not significantly differ between the control and hypertensive groups. The 24-h urinary sodium excretion of hypertensive patients was significantly higher than that of the control group (140.9 ± 59.8 vs. 117.9 ± 57.2 mEq/day, respectively, p  = 0.011). Also, the urinary sodium-potassium ratio was significantly higher in the hypertensive patients. There was no correlation between the salt-taste threshold and 24-h urinary sodium excretion. The salt-taste threshold might not be related to the BP status as well as the 24-h urinary sodium excretion.

Lowering urinary oxalate excretion to decrease calcium oxalate stone disease

PubMed Central

Knight, John; Assimos, Dean G.

2016-01-01

Dietary modifications should be considered as a first line approach in the treatment of idiopathic calcium oxalate nephrolithiasis. The amounts of oxalate and calcium consumed in the diet are significant factors in the development of the disease due to their impact on urinary oxalate excretion. There are a number of strategies that can be employed to reduce oxalate excretion. The consumption of oxalate-rich foods should be avoided and calcium intake adjusted to 1000–1200 mg/day. To encourage compliance it should be emphasized to patients that they be vigilant with this diet as a deviation in any meal or snack could potentially result in significant stone growth. The evidence underlying these two modifications is outlined and other strategies to reduce urinary oxalate excretion are reviewed. PMID:26614109

Effect of zeolite nano-materials and artichoke (Cynara scolymus L.) leaf extract on increase in urinary clearance of systematically absorbed nicotine.

PubMed

Malekshah, R E; Mahjub, R; Rastgarpanah, M; Ghorbani, M; Partoazar, A R; Mehr, S E; Dehpour, A R; Dorkoosh, F A

2012-12-01

Nicotine, the main pharmacologically active component in tobacco and cigarette, has some toxic effects and also high potential for addiction. In this study, the effect of artichoke (Cynara scolymus L.) and zeolite nano-materials on urinary excretion of nicotine and consequently elimination of systematically absorbed nicotine was investigated. A simple, valid and highly sensitive high performance liquid chromatography method has been developed for determination of nicotine in rat urine according to guidelines for bioanalysis.It was found that nano-zeolites can cause increase in urinary concentration of nicotine due to its high surface adsorption. Artichoke leaf extract can cause increase in urinary excretion of nicotine in longer post administration times. It was observed that co-administration of nanozeolites and the leaf extract has the synergetic effect on increasing the urinary excretion of nicotine. © Georg Thieme Verlag KG Stuttgart · New York.

Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion.

PubMed

Chang, Jae-Hyung; Paik, Seung-Yeol; Mao, Lan; Eisner, William; Flannery, Patrick J; Wang, Liming; Tang, Yuping; Mattocks, Natalie; Hadjadj, Samy; Goujon, Jean-Michel; Ruiz, Phillip; Gurley, Susan B; Spurney, Robert F

2012-01-01

Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process.

Diabetic Kidney Disease in FVB/NJ Akita Mice: Temporal Pattern of Kidney Injury and Urinary Nephrin Excretion

PubMed Central

Chang, Jae-Hyung; Paik, Seung-Yeol; Mao, Lan; Eisner, William; Flannery, Patrick J.; Wang, Liming; Tang, Yuping; Mattocks, Natalie; Hadjadj, Samy; Goujon, Jean-Michel; Ruiz, Phillip; Gurley, Susan B.; Spurney, Robert F.

2012-01-01

Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process. PMID:22496773

Urinary sodium excretion after gastric bypass surgery.

PubMed

Docherty, Neil G; Fändriks, Lars; le Roux, Carel W; Hallersund, Peter; Werling, Malin

2017-09-01

Gut-kidney signaling is implicated in sodium homeostasis and thus blood pressure regulation. Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity confers a pronounced and long-lasting blood pressure lowering effect in addition to significant weight loss. We set out to establish whether RYGB is associated with an intrinsic change in urinary sodium excretion that may contribute to the reported blood pressure lowering effects of the procedure. University hospital METHODS: Five female patients (age range: 28-50 yr) without metabolic or hypertensive co-morbidities were included in a study involving four 24-hour residential visits: once before surgery and 10 days, 3 months, and 20 months after surgery. Creatinine and sodium were measured in fasting plasma samples and 24-hour urine samples and creatinine clearance, estimated glomerular filtration rate, and indices of urinary sodium excretion were calculated. Fasting and 60-minute postprandial blood samples from each study day were assayed for pro-B-type natriuretic peptide (NT-proBNP). Increases in weight-normalized urinary sodium excretion of up to 2.3-fold in magnitude occurred at 20 months after surgery. Median fractional excretion of sodium at 20 months was double that seen before surgery. Fasting NT-proBNP levels were stable or increased (1.5- to 5-fold). Moreover, a small postprandial increase in NT-proBNP was observed after surgery. Renal fractional excretion of sodium is increased after RYGB. A shift toward increased postoperative basal and meal associated levels of NT-proBNP coincides with increased urinary sodium excretion. The data support a working hypothesis that an enhanced natriuretic gut-kidney signal after RYGB may be of mechanistic importance in the blood pressure lowering effects of this procedure. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Excess Vitamin Intake before Starvation does not Affect Body Mass, Organ Mass, or Blood Variables but Affects Urinary Excretion of Riboflavin in Starving Rats.

PubMed

Moriya, Aya; Fukuwatari, Tsutomu; Shibata, Katsumi

2013-01-01

B-vitamins are important for producing energy from amino acids, fatty acids, and glucose. The aim of this study was to elucidate the effects of excess vitamin intake before starvation on body mass, organ mass, blood, and biological variables as well as on urinary excretion of riboflavin in rats. Adult rats were fed two types of diets, one with a low vitamin content (minimum vitamin diet for optimum growth) and one with a sufficient amount of vitamins (excess vitamin diet). Body mass, organ mass, and blood variables were not affected by excess vitamin intake before starvation. Interestingly, urinary riboflavin excretion showed a different pattern. Urine riboflavin in the excess vitamin intake group declined gradually during starvation, whereas it increased in the low vitamin intake group. Excess vitamin intake before starvation does not affect body mass, organ mass, or blood variables but does affect the urinary excretion of riboflavin in starving rats.

Porphyrinuria in childhood autistic disorder: Implications for environmental toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nataf, Robert; Skorupka, Corinne; Amet, Lorene

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001).more » Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.« less

Porphyrinuria in childhood autistic disorder: implications for environmental toxicity.

PubMed

Nataf, Robert; Skorupka, Corinne; Amet, Lorene; Lam, Alain; Springbett, Anthea; Lathe, Richard

2006-07-15

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.

Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanczyk, F.Z.; Miyakawa, I.; Goebelsmann, U.

Assays measuring immunoreactive estrone glucuronide (E/sub 1/G), estradiol-3-glucuronide (E/sub 2/-3G), estradiol-17..beta..-glucuronide (E/sub 2/-17G), estriol-3-glucuronide (E/sub 3/-3G), estriol-16..cap alpha..-glucuronide (E/sub 3/-16G), and pregnanediol-3..cap alpha..-glucuronide (Pd-3G) directly in diluted urine were developed and validated. These estrogen and pregnanediol glucuronide fractions were measured in aliquots of 24-hour and overnight samples of urine collected daily from seven women for one menstrual cycle. Urinary hormone excretion was correlated with daily serum estradiol (E/sub 2/), progesterone (P), and lutenizing hormonee (LH) levels. A sharp midcycle LH peak preceded by a preovulatory rise in serum E/sub 2/ and followed by luteal phase serum P levels were notedmore » in each of the seven apparently ovulatory cycles. Twenty-four-hour and overnight urinary excretion patterns of estrogen glucuronides were similar to those of serum E/sub 2/. Of the five estrogen glucuronide fractions tested, excretion of E/sub 2/-17G exhibited the earliest and steepest ascending slope of the preovulatory estrogen surge and correlated best with serum E/sub 2/ levels. Urinary excretion of E/sub 1/-G, E/sub 2/-3G, and E/sub 3/-16G also showed an early and steep preovulatory rise and preceded that of E/sub 3/-3G, whereas urinary excretion of E/sub 3/-3G exhibited the poorest correlation with serum E/sub 2/ concentrations. The urinary excretion of Pd-3G rose parallel to serum P levels and was markedly elevated 2 to 3 days after the midcycle LH peak in both 24-hour and overnight collections of urine. These results indicate that among the urinary estrogen conjugate fractions tested, E/sub 2/-17G is the one that most suitably predicts ovulation.« less

Assessment of Urinary Betaine as a Marker of Diabetes Mellitus in Cardiovascular Patients

PubMed Central

Schartum-Hansen, Hall; Ueland, Per M.; Pedersen, Eva R.; Meyer, Klaus; Ebbing, Marta; Bleie, Øyvind; Svingen, Gard F. T.; Seifert, Reinhard; Vikse, Bjørn E.; Nygård, Ottar

2013-01-01

Abnormal urinary excretion of betaine has been demonstrated in patients with diabetes or metabolic syndrome. We aimed to identify the main predictors of excretion in cardiovascular patients and to make initial assessment of its feasibility as a risk marker of future diabetes development. We used data from 2396 patients participating in the Western Norway B-vitamin Intervention Trial, who delivered urine and blood samples at baseline, and in the majority at two visits during follow-up of median 39 months. Betaine in urine and plasma were measured by liquid-chromatography-tandem mass spectrometry. The strongest determinants of urinary betaine excretion by multiple regression were diabetes mellitus, age and estimated glomerular filtration rate; all p<0.001. Patients with diabetes mellitus (n = 264) had a median excretion more than three times higher than those without. We found a distinct non-linear association between urinary betaine excretion and glycated hemoglobin, with a break-point at 6.5%, and glycated hemoglobin was the strongest determinant of betaine excretion in patients with diabetes mellitus. The discriminatory power for diabetes mellitus corresponded to an area under the curve by receiver-operating characteristics of 0.82, and betaine excretion had a coefficient of reliability of 0.73. We also found a significant, independent log-linear relation between baseline betaine excretion and the risk of developing new diabetes during follow-up. The good discriminatory power for diabetes, high test-retest stability and independent association with future risk of new diabetes should motivate further investigation on the role of betaine excretion in risk assessment and long-term follow-up of diabetes mellitus. PMID:23936331

Urinary excretion of purine derivatives as an index of microbial protein synthesis in the camel (Camelus dromedarius).

PubMed

Guerouali, Abdelhai; El Gass, Youssef; Balcells, Joaquim; Belenguer, Alvaro; Nolan, John

2004-08-01

Five experiments were carried out to extend knowledge of purine metabolism in the camel (Camelus dromedarius) and to establish a model to enable microbial protein outflow from the forestomachs to be estimated from the urinary excretion of purine derivatives (PD; i.e. xanthine, hypoxanthine, uric acid, allantoin). In experiment 1, four camels were fasted for five consecutive days to enable endogenous PD excretion in urine to be determined. Total PD excretion decreased during the fasting period to 267 (SE 41.5) micromol/kg body weight (W)0.75 per d. Allantoin and xanthine + hypoxanthine were consistently 86 and 6.1 % of total urinary PD during this period but uric acid increased from 3.6 % to 7.4 %. Xanthine oxidase activity in tissues (experiment 2) was (micromol/min per g fresh tissue) 0.038 in liver and 0.005 in gut mucosa but was not detected in plasma. In experiment 3, the duodenal supply of yeast containing exogenous purines produced a linear increase in urinary PD excretion rate with the slope indicating that 0.63 was excreted in urine. After taking account of endogenous PD excretion, the relationship can be used to predict purine outflow from the rumen. From the latter prediction, and also the purine:protein ratio in bacteria determined in experiment 5, we predicted the net microbial outflow from the rumen. In experiment 4, with increasing food intake, the rate of PD excretion in the urine increased linearly by about 11.1 mmol PD/kg digestible organic matter intake (DOMI), equivalent to 95 g microbial protein/kg DOMI.

Acidosis and Urinary Calcium Excretion: Insights from Genetic Disorders

PubMed Central

Cordat, Emmanuelle; Chambrey, Régine; Dimke, Henrik; Eladari, Dominique

2016-01-01

Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis. PMID:27468975

Increased urinary excretion of platelet activating factor in mice with lupus nephritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macconi, D.; Noris, M.; Benfenati, E.

1991-01-01

Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-(1{prime},2{prime}-{sup 3}H)alkyl) is filtered through the glomerulus and excreted in the urine. The results show that:more » (1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, (2) PAF levels increased when animals started to develop high grade proteinuria, (3) after intravenous injection of ({sup 3}H) PAF In nephritic mice, a negligible amount of ({sup 3}H) ether lipid, corresponding to ({sup 3}H)1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.« less

A review on environmental factors regulating arsenic methylation in humans.

PubMed

Tseng, Chin-Hsiao

2009-03-15

Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers.

Farmworker and nonfarmworker Latino immigrant men in North Carolina have high levels of specific pesticide urinary metabolites.

PubMed

Arcury, Thomas A; Chen, Haiying; Laurienti, Paul J; Howard, Timothy D; Barr, Dana Boyd; Mora, Dana C; Quandt, Sara A

2017-06-16

This article compares detections and concentrations of specific organophosphate (OP), bis-dithiocarbamate, and pyrethroid pesticide urinary metabolites among Latino male farmworkers and nonfarmworkers in North Carolina. Data are from interviews and urine samples collected in 2012 and 2013. Farmworkers and nonfarmworkers frequently had detections for OP and pyrethroid pesticide urinary metabolites. Detection of bis-dithiocarbamate urinary metabolites was less frequent, but substantial among the nonfarmworkers. The concentrations of organophosphate, bis-dithiocarbamate, and pyrethroid pesticide urinary metabolites were high for farmworkers and nonfarmworkers compared to National Health and Nutrition Examination Survey results. Pesticide urinary metabolite detection was not associated with occupation in nonfarmworkers. Research for reducing pesticide exposure among farmworkers remains important; research is also needed to determine pesticide exposure pathways among Latino nonfarmworkers.

Changes in urinary risk profile after short-term low sodium and low calcium diet in recurrent Swiss kidney stone formers.

PubMed

Seeger, Harald; Kaelin, Andrea; Ferraro, Pietro M; Weber, Damian; Jaeger, Philippe; Ambuehl, Patrice; Robertson, William G; Unwin, Robert; Wagner, Carsten A; Mohebbi, Nilufar

2017-12-04

Kidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates. While hypercalciuria is a well-known risk factor, restricted intake of animal protein and sodium, combined with normal dietary calcium, has been shown to be more effective in stone prevention compared with a low-calcium diet. Notably, the average sodium intake in Switzerland is twice as high as the WHO recommendation, while the intake of milk and dairy products is low. We retrospectively analyzed Swiss recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in combination with a low-calcium diet on the urinary risk profile. In patients with recurrent calcium oxalate containing stones, we investigated both, the consequence of a low-sodium diet on urinary volume and calcium excretion, and the influence of a low-sodium low-calcium diet on urinary oxalate excretion. Of the 169 patients with CaOx stones, 49 presented with hypercalciuria at baseline. The diet resulted in a highly significant reduction in 24-h urinary sodium and calcium excretion: from 201 ± 89 at baseline to 128 ± 88 mmol/d for sodium (p < 0.0001), and from 5.67 ± 3.01 to 4.06 ± 2.46 mmol/d (p < 0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no increase in oxalate excretion occurred on the restricted diet (0.39 ± 0.26 vs 0.39 ± 0.19 mmol/d, p = 0.277). Calculated Psf (probability of stone formation) values were only predictive for the risk of calcium phosphate stones. A diet low in sodium and calcium in recurrent calcium oxalate stone formers resulted in a significant reduction of urinary calcium excretion, but no change in urine volume. In this population with apparently low intake of dairy products, calcium restriction does not necessarily result in increased urinary oxalate excretion. However, based on previous studies, we recommend a normal dietary calcium intake to avoid a potential increase in urinary oxalate excretion and unfavorable effects on bone metabolism in hypercalciuric KSFs.

Effect of Roux-en-Y gastric bypass and diet-induced weight loss on diabetic kidney disease in the Zucker diabetic fatty rat.

PubMed

Neff, Karl J; Elliott, Jessie A; Corteville, Caroline; Abegg, Kathrin; Boza, Camilo; Lutz, Thomas A; Docherty, Neil G; le Roux, Carel W

2017-01-01

Reductions in urinary protein excretion after Roux-en-Y gastric bypass (RYGB) surgery in patients with diabetic kidney disease have been reported in multiple studies. To determine the weight loss dependence of the effect of RYGB on urinary protein excretion by comparing renal outcomes in Zucker diabetic fatty rats undergoing either gastric bypass surgery or a sham operation with or without weight matching. University laboratories. Zucker diabetic fatty rats underwent surgery at 18 weeks of age. A subgroup of sham operated rats were weight matched to RYGB operated rats by restricting food intake. Urinary protein excretion was assessed at baseline and at postoperative weeks 4 and 12. Renal histology and macrophage-associated inflammation were assessed at postoperative week 12. Progressive urinary protein excretion was attenuated by both RYGB and diet-induced weight loss, albeit to a lesser extent by the latter. Both weight loss interventions produced equivalent reductions in glomerulomegaly, glomerulosclerosis, and evidence of renal macrophage infiltration. Weight loss per se improves renal structure and attenuates renal inflammatory responses in an experimental animal model of diabetic kidney disease. Better glycemic control post-RYGB may in part explain the greater reductions in urinary protein excretion after gastric bypass surgery. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.

2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a novel refrigerant intended for use in mobile air conditioning. It showed a low potential for toxicity in rodents studies with most NOAELs well above 10,000 ppm in guideline compliant toxicity studies. However, a developmental toxicity study in rabbits showed mortality at exposure levels of 5,500 ppm and above. No lethality was observed at exposure levels of 2,500 and 4,000 ppm. Nevertheless, increased subacute inflammatory heart lesions were observed in rabbits at all exposure levels. Since the lethality in pregnant animals may be due to altered biotransformation of HFO-1234yf and to evaluate the potential risk to pregnantmore » women facing a car crash, this study compared the acute toxicity and biotransformation of HFO-1234yf in male, female and pregnant female rabbits. Animals were exposed to 50,000 ppm and 100,000 ppm for 1 h. For metabolite identification by {sup 19}F NMR and LC/MS-MS, urine was collected for 48 h after inhalation exposure. In all samples, the predominant metabolites were S-(3,3,3-trifluoro-2-hydroxypropanyl)-mercaptolactic acid and N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine. Since no major differences in urinary metabolite pattern were observed between the groups, only N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-L-cysteine excretion was quantified. No significant differences in recovery between non-pregnant (43.10 ± 22.35 μmol) and pregnant female (50.47 ± 19.72 μmol) rabbits were observed, male rabbits exposed to 100,000 ppm for one hour excreted 86.40 ± 38.87 μmol. Lethality and clinical signs of toxicity were not observed in any group. The results suggest that the lethality of HFO-1234yf in pregnant rabbits unlikely is due to changes in biotransformation patterns or capacity in pregnant rabbits. -- Highlights: ► No lethality and clinical signs were observed. ► No differences in metabolic pattern between pregnant and non-pregnant rabbits. ► Rapid and similar metabolite excretion in all groups. ► Very low amount of biotransformation in all groups (< 0.1%).« less

Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

PubMed

Haas, C S; Rahvar, A-H; Danneberg, S; Lehnert, H; Moenig, H; Harbeck, B

2016-09-01

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 μg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 μg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency. © Georg Thieme Verlag KG Stuttgart · New York.

Pharmacokinetics of doxylamine, a component of Bendectin, in the rhesus monkey.

PubMed

Slikker, W; Holder, C L; Lipe, G W; Bailey, J R; Young, J F

1989-01-01

The elimination of doxylamine and metabolites was determined after iv administration of [14C]doxylamine succinate at 0.7 and 13.3 mg/kg to the adult female rhesus monkey. Although the total recovery of radioactivity was the same for the low- and high-dose studies (90.2%), the rate of plasma elimination of doxylamine and its demethylated metabolite (desmethyldoxylamine) was slower for the high dose group. The 24 hr urinary excretion of doxylamine metabolites, desmethyl- and didesmethyldoxylamine, was significantly increased and the polar doxylamine metabolites were significantly decreased as the iv doxylamine succinate dose was increased. The plasma elimination of gas chromatograph (GC)-detected doxylamine was determined after oral administration of Bendectin (doxylamine succinate and pyridoxine hydrochloride) at 7, 13.3, and 27 mg/kg to adult female rhesus monkeys. As the dose increased, the clearance of doxylamine decreased. A statistically evaluated fit of the oral data to a single-compartment, parallel first-order elimination model and a single-compartment, parallel first- and second-order (Michaelis-Menten) elimination model indicated that the more complex model containing the second-order process was most consistent with the observed elimination data.

Endocrine relationships during human spaceflight

NASA Technical Reports Server (NTRS)

Stein, T. P.; Schluter, M. D.; Moldawer, L. L.

1999-01-01

Human spaceflight is associated with a chronic loss of protein from muscle. The objective of this study was to determine whether changes in urinary hormone excretion could identify a hormonal role for this loss. Urine samples were collected from the crews of two Life Sciences Space Shuttle missions before and during spaceflight. Data are means +/- SE with the number of subjects in parentheses. The first value is the mean preflight measurement, and the second value is the mean inflight measurement. Adrenocorticotropic hormone (ACTH) [27.7 +/- 4.4 (9) vs. 25.1 +/- 3.4 (9) ng/day], growth hormone [724 +/- 251 (9) vs. 710 +/- 206 (9) ng/day], insulin-like growth factor I [6.81 +/- 0.62 vs. 6.04 +/- 0.51 (8) nM/day], and C-peptide [44.9 +/- 8.3 (9) vs. 50.7 +/- 10.3 (9) micrograms/day] were unchanged with spaceflight. In contrast, free 3,5,3'-triiodothyronine [791 +/- 159 (9) vs. 371 +/- 41 (9) pg/day, P < 0.05], prostaglandin E2 (PGE2) [1, 064 +/- 391 (8) vs. 465 +/- 146 (8) ng/day, P < 0.05], and its metabolite PGE-M [1,015 +/- 98 (9) vs. 678 +/- 105 (9) ng/day, P < 0. 05] were decreased inflight. The urinary excretion of most hormones returned to their preflight levels during the postflight period, with the exception of ACTH [47.5 +/- 10.3 (9) ng/day], PGE2 [1,433 +/- 327 (8) ng/day], PGF2alpha, [2,786 +/- 313 (8) ng/day], and its metabolite PGF-M [4,814 +/- 402 (9) ng/day], which were all increased compared with the preflight measurement (P < 0.05). There was a trend for urinary cortisol to be elevated inflight [55.3 +/- 5. 9 (9) vs. 72.5 +/- 11.1 micrograms/day, P = 0.27] and postflight [82.7 +/- 8.6 (8) micrograms/day, P = 0.13]. The inflight human data support ground-based in vitro work showing that prostaglandins have a major role in modulating the changes in muscle protein content in response to tension or the lack thereof.

Hypertension and Hyperglycemia Synergize to Cause Incipient Renal Tubular Alterations Resulting in Increased NGAL Urinary Excretion in Rats

PubMed Central

Blázquez-Medela, Ana M.; García-Sánchez, Omar; Blanco-Gozalo, Víctor; Quiros, Yaremi; Montero, María J.; Martínez-Salgado, Carlos; López-Novoa, José M.; López-Hernández, Francisco J.

2014-01-01

Background Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner. Methods Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR) or L-NAME induced hypertension rendered hyperglycemic (or not as controls). Results Combination of hypertension and hyperglycemia (but not each of these factors independently) causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors. Conclusions Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion. PMID:25148248

Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

PubMed

Blázquez-Medela, Ana M; García-Sánchez, Omar; Blanco-Gozalo, Víctor; Quiros, Yaremi; Montero, María J; Martínez-Salgado, Carlos; López-Novoa, José M; López-Hernández, Francisco J

2014-01-01

Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner. Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR) or L-NAME induced hypertension rendered hyperglycemic (or not as controls). Combination of hypertension and hyperglycemia (but not each of these factors independently) causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors. Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

Evolution of urinary iodine excretion over eleven years in an adult population.

PubMed

Gutiérrez-Repiso, Carolina; Colomo, Natalia; Rojo-Martinez, Gemma; Valdés, Sergio; Tapia, Maria J; Esteva, Isabel; Ruiz de Adana, Maria S; Rubio-Martin, Elehazara; Lago-Sampedro, Ana; Santiago, Piedad; Velasco, Ines; Garcia-Fuentes, Eduardo; Moreno, Jose C; Soriguer, Federico

2015-08-01

Few prospective cohort studies have evaluated dietary iodine intake and urinary iodine concentrations in the general adult population. We assess the evolution of urinary iodine excretion and factors that may influence it in an adult population followed for 11 years. A population-based cohort study was undertaken in Pizarra (Spain). In the three study phases (baseline (n = 886), and 6 (n = 788) and 11 years later (n = 501)), participants underwent an interview and a standardized clinical examination that included a food questionnaire, and thyroid hormone and urinary iodine determinations. Subjects with thyroid dysfunction, palpable goiter or urinary iodine excretion >400 μg/L were excluded. Urinary iodine increased over the years (100.6 ± 70.0 μg/L at baseline vs. 125.4 ± 95.2 μg/L at 6 years and 141.6 ± 81.4 μg/L at 11 years; p < 0.0001). Urinary iodine was significantly higher in subjects who reported iodized salt consumption and in subjects with a higher intake of dairy products (p < 0.05). Consumption of iodized salt (Risk ratio (RR) = 1.23, 95% CI [1.01-2.05]) and dairy products (RR = 2.07, 95% CI [1.01-4.23]), and a baseline urinary iodine concentration ≥100 μg/L (RR = 1.26, 95% CI [1.04-1.53]) were significantly associated with urinary iodine concentrations ≥100 μg/L at 11 years. There is no correlation between thyroid function (TSH, free triiodothyronine or free thyroxine levels) and urinary iodine concentrations in conditions of iodine sufficiency. The increase in urinary iodine concentrations over eleven years is associated with an increase in iodized salt intake and with the dairy products intake, and possibly with a higher iodine content of dairy products. However, individual variability in urinary iodine excretion was not fully explained by dietary iodine intake alone; previous urinary iodine concentrations were also important. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Metabolism, Distribution, and Elimination of Mequindox in Pigs, Chickens, and Rats.

PubMed

Huang, Lingli; Yin, Fujun; Pan, Yuanhu; Chen, Dongmei; Li, Juan; Wan, Dan; Liu, Zhenli; Yuan, Zonghui

2015-11-11

Mequindox (MEQ), a quinoxaline-N,N-dioxide antibacterial agent used to control bacterial enteritis in various food-producing animals, is a potential violative residue in food animal-derived products. The disposition and elimination of MEQ in rats, pigs, and chickens was comprehensively investigated to identify the marker residue and target tissue of MEQ in food animals for residue monitoring. Following a single oral administration, 62-71% of MEQ was rapidly excreted via urine and feces in all species within 24 h. Urinary excretion of radioactivity was 84 and 83.5% of the administered dose in rats and pigs, respectively. More than 92% of the administered dose was excreted in all species within 15 days. Radioactivity was found in nearly all tissues at the first 6 h after dosing, with the majority of radioactivity cleared within 4-6 days. The highest radioactivity and longest persisting time were found to be in the liver and kidney. Totals of 11, 12, and 7 metabolites were identified in rats, chickens, and pigs, respectively. No parent drug could be detected in any of the tissues of pigs and chickens. 3-Methyl-2-acetyl quinoxaline (M1), 3-methyl-2-(1-hydroxyethyl) quinoxaline-N4-monoxide (M4), and 3-methyl-2-(1-hydroxyethyl) quinoxaline-1,4-dioxide (M6) were the common and major metabolites of MEQ in all three species. Additionally, 3-methyl-2-(1-hydroxyethyl) quinoxaline (M5), 3-hydroxymethyl-2-ethanol quinoxaline-1,4-dioxide (M7), and 3-methyl-2-(1-hydroxyethyl) quinoxaline-N1-monoxide (M8) were the major metabolites of MEQ in rats, pigs, and chickens, respectively. M1 was designated to be the marker residue of MEQ in pigs and chickens. These results provide scientific data for the determination of marker residues and withdrawal time of MEQ in food animals and improve the understanding of the toxicity and disposition of MEQ in animals.

Increasing alkali supplementation decreases urinary nitrogen excretion when adjusted for same day nitrogen intake

USDA-ARS?s Scientific Manuscript database

Summary: We examined whether escalating doses of potassium bicarbonate (KHCO3) supplements alter urinary nitrogen excretion expressed as a ratio to same day nitrogen intake (measure of muscle-protein breakdown). The ratio declined significantly from placebo to low to high dose of KHCO3 supplementati...

Study of tamoxifen urinary metabolites in rat by ultra-high-performance liquid chromatography time-of-flight mass spectrometry.

PubMed

Domínguez-Romero, Juan C; García-Reyes, Juan F; Beneito-Cambra, Miriam; Martínez-Romero, Rubén; Martinez-Lara, Esther; Del Moral-Leal, María L; Molina-Díaz, Antonio

2015-08-01

Tamoxifen (TMX) is a nonsteroidal estrogen antagonist drug used for the treatment of breast cancer. It is also included in the list of banned substances of the World Anti Doping Agency (WADA) prohibited in and out of competition. In this work, the excretion of urinary metabolites of TMX after a single therapeutic dose administration in rats has been studied using ultra-high-performance liquid chromatography electrospray time-of-flight mass spectrometry (UHPLC-TOFMS). A systematic strategy based on the search of typical biotransformations that a xenobiotic can undergo in living organisms, based on their corresponding molecular formula modification and accurate mass shifts, was applied for the identification of TMX metabolites. Prior to UHPLC-TOFMS analyses, a solid-phase extraction step with polymeric cartridges was applied to urine samples. Up to 38 TMX metabolites were detected. Additional collision induced dissociation (CID) MS/MS fragmentation was performed using UHPLC-QTOFMS. Compared with recent previous studies in human urine and plasma, new metabolites have been reported for the first time in urine. Metabolites identified in rat urine include the oxygen addition, owing to different possibilities for the hydroxylation of the rings in different positions (m/z 388.2271), the incorporation of two oxygen atoms (m/z 404.2220) (including dihydroxylated derivatives or alternatives such as epoxidation plus hydroxylation or N-oxidation and hydroxylation), epoxide formation or hydroxylation and dehydrogenation [m/z 386.2114 (+O -H2 )], hydroxylation of the ring accompanied by N-desmethylation (m/z 374.2115), combined hydroxylation and methoxylation (m/z 418.2377), desaturated TMX derivate (m/z 370.2165) and its N-desmethylated derivate (m/z 356.2009), the two latter modifications not previously being reported in urine. These findings confirm the usefulness of the proposed approach based on UHPLC-TOFMS. Copyright © 2015 John Wiley & Sons, Ltd.

[Effects of excess nicotinic acid on growth and the urinary excretion of B-group vitamins and the metabolism of tryptophan in weaning rats].

PubMed

Fukuwatari, Tsutomu; Kurata, Kaori; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake level of nicotinic acid in humans, we investigated the effects of excess nicotinic acid administration on body weight gain, food intake, and urinary excretion of water-soluble vitamins and the metabolism of tryptophan in weaning rats. The weaning rats were freely fed a niacin-free 20% casein diet (control diet) or the same diet with 0.1%, 0.3% or 0.5% nicotinic acid for 23 days. The excess nicotinic acid intake did not affect body weight gain, food intake, serotonin contents in the brain, stomach and small intestine, or the urinary excretions of water-soluble vitamins. Although excess nicotinic acid did not affect the upper part of the tryptophan-nicotinamide pathway, 0.5% nicotinic acid diet increased the urinary excretion of quinolinic acid. The diet containing more than 0.3% nicotinic acid also increased the urinary excretion of nicotinic acid, which is usually below the limit of detection. As determined from the results of body weight gain and food intake as indices for apparent adverse effects, the no-observed-adverse-effect-level (NOAEL) for nicotinic acid was 0.5% in diet, corresponding to 450 mg/kg body weight/day. As judged from in increase of urinary quinolinic acid and nicotinic acid as indices of metabolic change, NOAEL was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and the lowest-observed-adverse-effect-level (LOAEL) was 0.3% in diet, corresponding to 270 mg/kg body weight/day.

Biotransformation and pharmacokinetics of the nitrate trans-2-amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide in dogs.

PubMed

Pressmar, F; Neidlein, R; Strein, K

1992-11-01

The biotransformation and the pharmacokinetic behavior of the organic nitrate trans-2-Amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide (BM 12.1179, CAS 129795-96-6) were examined in dogs. BM 12.1179 was predominantly eliminated by urinary excretion, and the unchanged molecule prevailed in urine as well as in plasma. By means of various mass spectroscopic methods, the chemical structures of the metabolites were elucidated. As metabolites trans-2-amino-2-methyl-N-(4-hydroxycyclohexyl)-propionamide and trans-2-amino-2-methyl-N-(4-oxocyclohexyl)-propionamide were formed. Urine levels of the main metabolite were determined by high-pressure liquid chromatography; plasma and urine levels of BM 12.1179 were determined by capillary gas chromatography. The absolute bioavailability of BM 12.1179 was 80-100%. The plasma protein binding was about 34% which is high in comparison to other organic nitrates. BM 12.1179 represents a long-acting organic nitrate in that it shows a slow reductive denitration, and a long elimination half-life of about 10 h.

Metabolism of isotretinoin. Biliary excretion of isotretinoin glucuronide in the rat.

PubMed

Meloche, S; Besner, J G

1986-01-01

The biliary metabolites of isotretinoin were examined after iv administration of 4-20-mg/kg doses to vitamin A-normal bile duct-cannulated rats. Analysis of bile by reverse phase high performance liquid chromatography showed that injection of isotretinoin is followed by a rapid excretion of metabolites in bile. Isotretinoin glucuronide was identified as the major metabolite in bile. A specific high performance liquid chromatography method based on the assay of generated isotretinoin in beta-glucuronidase-treated bile was developed for the determination of isotretinoin glucuronide in bile samples. The excretion rate of isotretinoin glucuronide increased rapidly to reach a maximum 55 min after dosing and then declined exponentially. After 330 min of collection, biliary excretion of isotretinoin glucuronide was almost complete, and the metabolite accounted for 34.8-37.9% of the dose. These results indicate that conjugation with glucuronic acid represents a major pathway for the metabolism of pharmacological doses of isotretinoin. The maximum excretion rate of isotretinoin glucuronide in bile increased in a linear manner with the dose of isotretinoin, and no delay was observed after the larger doses. These data suggest that glucuronidation and biliary excretion are not saturated at high pharmacological doses of isotretinoin.

Potential Uses of Biomonitoring Data: A Case Study Using the Organophosphorus Pesticides Chlorpyrifos and Malathion

PubMed Central

Barr, Dana B.; Angerer, Jürgen

2006-01-01

Background Organophosphorus pesticides such as chlorpyrifos and malathion are widely used insecticides. They do not bioaccumulate appreciably in humans and are rapidly metabolized and excreted in the urine. In nonoccupational settings, exposures to these pesticides are typically sporadic and short-lived because the pesticides tend to degrade in the environment over time; however, dietary exposures may be more chronic. Biologic monitoring has been widely used to assess exposures, susceptibility, and effects of chlorpyrifos and malathion; thus, the information base on these compounds is data rich. For biomonitoring of exposure, chlorpyrifos and malathion have been measured in blood, but most typically their urinary metabolites have been measured. For assessing early effects and susceptibility, cholinesterase and microsomal esterase activities, respectively, have been measured. Objectives Although many biologic monitoring data have been generated and published on these chemicals, their interpretation is not straightforward. For example, exposure to environmental degradates of chlorpyrifos and malathion may potentially increase f urinary metabolite levels, thus leading to overestimation of exposure. Also, the temporal nature of the exposures makes the evaluation of both exposure and effects difficult. We present an overview of the current biomonitoring and other relevant data available on exposure to chlorpyrifos and malathion and the use of these data in various environmental public health applications. PMID:17107865

Urinary Excretion of Sodium, Nitrogen, and Sugar Amounts Are Valid Biomarkers of Dietary Sodium, Protein, and High Sugar Intake in Nonobese Adolescents.

PubMed

Moore, Lori B; Liu, Sarah V; Halliday, Tanya M; Neilson, Andrew P; Hedrick, Valisa E; Davy, Brenda M

2017-12-01

Background: Objective indicators of dietary intake (e.g., biomarkers) are needed to overcome the limitations of self-reported dietary intake assessment methods in adolescents. To our knowledge, no controlled feeding studies to date have evaluated the validity of urinary sodium, nitrogen, or sugar excretion as dietary biomarkers in adolescents. Objective: This investigation aimed to evaluate the validity of urinary sodium, nitrogen, and total sugars (TS) excretion as biomarkers for sodium, protein, and added sugars (AS) intake in nonobese adolescents. Methods: In a crossover controlled feeding study design, 33 adolescents [12-18 y of age, 47 ± 25th percentile (mean ± SD) of body mass index (BMI; in kg/m 2 ) for age] consumed 5% AS [low added sugars (LAS)] and 25% AS [high added sugars (HAS)] isocaloric, macronutrient-matched (55% carbohydrate, 30% fat, and 15% protein) diets for 7 d each, in a randomly assigned order, with a 4-wk washout period between diets. On the final 2 d of each diet period, 24-h urine samples were collected. Thirty-two adolescents completed all measurements (97% retention). Results: Urinary sodium was not different from the expected 90% recovery (mean ± SD: 88% ± 18%, P = 0.50). Urinary nitrogen was correlated with protein intake ( r = 0.69, P < 0.001), although it was below the 80% expected recovery (62% ± 7%, P < 0.001). Urinary TS values were correlated with AS intake during the HAS diet ( r = 0.77, P < 0.001) and had a higher R 2 value of 0.28 than did AS intake ( R 2 = 0.36). TS excretion differed between LAS (0.226 ± 0.09 mg/d) and HAS (0.365 ± 0.16 mg/d) feeding periods ( P < 0.001). Conclusions: Urinary sodium appears to be a valid biomarker for sodium intake in nonobese adolescents. Urinary nitrogen is associated with protein intake, but nitrogen excretion rates were less than previously reported for adults, possibly owing to adolescent growth rates. TS excretion reflects AS at 25% AS intake and was responsive to the change in AS intake. Thus, urinary biomarkers are promising objective indicators of dietary intake in adolescents, although larger-scale feeding trials are needed to confirm these findings. This trial was registered at clinicaltrials.gov as NCT02455388. © 2017 American Society for Nutrition.

Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation.

PubMed

Chandurkar, Vikram; Shik, John; Randell, Edward

2008-01-01

To describe a patient with excess urinary thyroxine (T4) excretion and worsening of preexisting hypothyroidism in the setting of nephrotic syndrome and to determine whether excess urinary T4 excretion is present in other patients with proteinuria. We present data regarding the patient's initial presentation, diagnostic studies, and course of her illness. We suspected urinary T4 loss to be the cause of her presentation and analyzed her urine sample for total T4. We also analyzed differences in urinary T4 excretion in 22 patients with proteinuria and 16 control patients without proteinuria. Relevant medical literature is reviewed. A 44-year-old woman presented with a 3-month history of increasing fluid retention, weight gain, and fatigue. She had long-standing hypothyroidism on a stable levothyroxine dosage, 125 mcg/d. She had gained 27 kg and had developed significant edema. She had a grossly elevated thyroid-stimulating hormone level of 91 mIU/L. Her condition worsened, and a urinary protein measurement was 14.06 g/24 h-diagnostic of nephrotic syndrome. The levothyroxine dosage was increased to 225 mcg/d. Urinary total T4 concentration in a 24-hour sample was 59.0 microg/L (83.1 microg/24 h), indicating that a substantial fraction of her orally ingested T4 was lost in urine. Urinary total T4 excretion was significantly higher in patients with proteinuria (mean +/- standard deviation, 18.0 +/- 18.2 microg/L) vs control patients without proteinuria (mean, 3.8 +/- 1.8 microg/L) (P = .0014). In the patient described, urinary T4 loss due to proteinuria and nephrotic syndrome resulted in a severe exacerbation of underlying hypothyroidism.

Disposition, metabolism, and pharmacodynamics of labetalol in adult sheep.

PubMed

Yeleswaram, K; Rurak, D W; Kwan, E; Hall, C; Doroudian, A; Abbott, F S; Axelson, J E

1993-01-01

Labetalol causes significant maternal and fetal metabolic effects in pregnant sheep (Yeleswaram et al., J. Pharmacol. Exp. Ther. 262, 683-691 (1992)). This study was undertaken to investigate the contribution of skeletal muscles in the development of metabolic acidosis induced by labetalol and to explore the involvement of active metabolite(s) using conscious, chronically instrumented adult nonpregnant ewes. Following a 100 mg iv bolus, the disposition of labetalol was similar to that observed in pregnant sheep. The effects of labetalol included hypotension, reflex tachycardia, a significant increase in femoral blood flow, hyperglycemia, lactic acidosis, and increased hind limb oxygen consumption. The arteriovenous flux of labetalol, glucose, lactate, and oxygen across the hindlimb was calculated using the Fick principle. The net output of lactate from the hindquarter over 12 hr following drug administration was calculated to be 6.25 +/- 1.35 g (0.07 +/- 0.015 mol). Glucuronidation, sulfation, and oxidative metabolism of labetalol were studied using urine and bile samples. The cumulative urinary excretion of labetalol as unchanged drug, glucuronide and sulfate was found to be 1.61 +/- 0.3, 11.46 +/- 2.83, and 1.47 +/- 0.74% of the dose, respectively. Using GC-mass selective detection, the presence of 3-amino-1-phenylbutane (3-APB), a close congener of amphetamine, in urine and bile samples was established. The cumulative excretion of 3-APB in urine represents 0.044 +/- 0.016% of the dose. Pharmacokinetic analysis shows the apparent elimination half-life of the metabolite to be 13.5 +/- 3.8 min. Conjugates of 3-APB were also found in the bile and urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary thioether of employees of a chemical plant.

PubMed

Vainio, H; Savolainen, H; Kilpikari, I

1978-08-01

The thiols in the morning urine of 224 employees of a chemical plant were determined after alkaline hydrolysis of all urinary thioethers. The highest thioether excretion was found in rubber workers and radial tyre builders in comparison with clerks, plastic monomer mixers and footwear preparers. Smoking and medication tended to increase thioether excretion. Urinary thioether determination may prove to be a valuable tool in assessing exposure to mixtures of chemicals regardless of the route of absorption.

Urinary thioether of employees of a chemical plant.

PubMed Central

Vainio, H; Savolainen, H; Kilpikari, I

1978-01-01

The thiols in the morning urine of 224 employees of a chemical plant were determined after alkaline hydrolysis of all urinary thioethers. The highest thioether excretion was found in rubber workers and radial tyre builders in comparison with clerks, plastic monomer mixers and footwear preparers. Smoking and medication tended to increase thioether excretion. Urinary thioether determination may prove to be a valuable tool in assessing exposure to mixtures of chemicals regardless of the route of absorption. PMID:698138

Supplementation of alfalfa (Medicago sativa) with condensed tannin-containing pellets of sericea lespedeza (Lespedeza cuneata): Effects on ruminant urinary urea excretion and digestibility

USDA-ARS?s Scientific Manuscript database

Some feedstuffs that contain condensed tannins can reduce urinary urea excretion without compromising nutrition for ruminant livestock. This results in reducing environmental impact, improving productivity and enhancing sustainability of ruminant farming operations. In some situations there are adva...

Biological monitoring of isocyanates and related amines. I. Determination of 1,6-hexamethylene diamine (HDA) in hydrolysed human urine after oral administration of HDA.

PubMed

Brorson, T; Skarping, G; Sandström, J F; Stenberg, M

1990-01-01

1,6-Hexamethylene diamine (HDA), used as raw material in industrial manufacturing operations, was orally administered to six healthy volunteers. After acid hydrolysis of the urine by hydrochloric acid, HDA and the metabolite 6-aminohexanoic acid were quantified. HDA was determined as an ethyl-chloroformate derivative by capillary gas chromatography using thermionic specific detection (TSD), and 6-aminohexanoic acid was quantified by ion chromatography using the ninhydrin reaction. In nonhydrolysed urine, monoacetylated HDA (N-acetyl-1,6-hexamethylene diamine) and HDA, were verified as heptafluorobutyric anhydride derivatives by gas chromatography-mass spectrometry (GC-MS), in a chemical ionization mode using isobutane and ammonia as reagent gases. In hydrolysed urine, a mean of 0.28 mg (range 1-6%) of the administered dose (8.2 mg) was recovered as HDA, and a mean of 0.8 mg (range less than 1-27%) as 6-aminohexanoic acid. The urinary excretion of both the determined compounds was rapid, and the principal part (greater than 90%) of the elimination was completed within 10 h. There was a considerable inter-individual variation in the excreted amounts, but the intra-individual variation in the excretion of HDA was limited. The subjects N-acetylator phenotype was determined by a dapsone test. Three slow acetylators excreted lower amounts (mean 2% of given dose) of HDA than three rapid ones (mean 5%).

Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts

PubMed Central

Friedrich, Nele; Pietzner, Maik; Cannet, Claire; Thuesen, Betina H.; Hansen, Torben; Wallaschofski, Henri; Grarup, Niels; Skaaby, Tea; Budde, Kathrin; Pedersen, Oluf; Nauck, Matthias; Linneberg, Allan

2017-01-01

Background Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH). Methods Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function. Results Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values. Conclusion The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research. PMID:28253303

Relationship between plasma uridine and urinary urea excretion.

PubMed

Ka, Tuneyoshi; Inokuchi, Taku; Tamada, Daisuke; Suda, Michio; Tsutsumi, Zenta; Okuda, Chihiro; Yamamoto, Asako; Takahashi, Sumio; Moriwaki, Yuji; Yamamoto, Tetsuya

2010-03-01

To investigate whether the concentration of uridine in plasma is related to the urinary excretion of urea, 45 healthy male subjects with normouricemia and normal blood pressure were studied after providing informed consent. Immediately after collection of 24-hour urine, blood samples were drawn after an overnight fast except for water. The contents of ingested foods during the 24-hour urine collection period were described by the subjects and analyzed by a dietician. Simple regression analysis showed that plasma uridine was correlated with the urinary excretions of urea (R = 0.41, P < .01), uric acid (R = 0.36, P < .05), and uridine (R = 0.30, P < .05), as well as uric acid clearance (R = 0.35, P < .05) and purine intake (R = 0.30, P < .05). In contrast, multiple regression analysis showed a positive relationship only between plasma uridine and urinary excretion of urea. These results suggest that an increase in de novo pyrimidine synthesis leads to an increased concentration of uridine in plasma via nitrogen catabolism in healthy subjects with normouricemia and normal blood pressure. (c) 2010 Elsevier Inc. All rights reserved.

Effect of dietary supplementation of gallic acid on nitrogen balance, nitrogen excretion pattern and urinary nitrogenous constituents in beef cattle.

PubMed

Wei, Chen; Yang, Kai; Zhao, Guangyong; Lin, Shixin; Xu, Zhiwei

2016-10-01

The objective of the trial was to study the effects of dietary supplementation of gallic acid (GA) on nitrogen (N) balance, N excretion pattern and urinary N constituents in beef cattle. In a 4 × 4 Latin square design, four male 30-month-old Simmental cattle (443 ± 22 kg live weight) received four levels of GA (purity ≥ 98.5%), i.e. 0, 5.3, 10.5, 21.1 g/kg DM, added to a basal ration. Each experimental period lasted 17 d, consisting of 12 d adaptation and 5 d sampling. The results showed that supplementation of GA at 5.3, 10.5 or 21.1 g/kg DM did not affect the N balance but regulated the N excretion pattern by increasing the ratio of faecal N/urinary N and decreasing the ratio of urinary urea N/total urinary N in beef cattle fed at maintenance level.

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

PubMed

Araki, S; Aono, H; Murata, K

1986-09-01

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings.

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

PubMed Central

Araki, S; Aono, H; Murata, K

1986-01-01

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings. PMID:3092853

Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter

PubMed Central

Gjymishka, Altin; Salido, Eduardo C.; Allison, Milton J.; Freel, Robert W.

2011-01-01

Oxalobacter colonization of rat intestine was previously shown to promote enteric oxalate secretion and elimination, leading to significant reductions in urinary oxalate excretion (Hatch et al. Kidney Int 69: 691–698, 2006). The main goal of the present study, using a mouse model of primary hyperoxaluria type 1 (PH1), was to test the hypothesis that colonization of the mouse gut by Oxalobacter formigenes could enhance enteric oxalate secretion and effectively reduce the hyperoxaluria associated with this genetic disease. Wild-type (WT) mice and mice deficient in liver alanine-glyoxylate aminotransferase (Agxt) exhibiting hyperoxalemia and hyperoxaluria were used in these studies. We compared the unidirectional and net fluxes of oxalate across isolated, short-circuited large intestine of artificially colonized and noncolonized mice. In addition, plasma and urinary oxalate was determined. Our results demonstrate that the cecum and distal colon contribute significantly to enteric oxalate excretion in Oxalobacter-colonized Agxt and WT mice. In colonized Agxt mice, urinary oxalate excretion was reduced 50% (to within the normal range observed for WT mice). Moreover, plasma oxalate concentrations in Agxt mice were also normalized (reduced 50%). Colonization of WT mice was also associated with marked (up to 95%) reductions in urinary oxalate excretion. We conclude that segment-specific effects of Oxalobacter on intestinal oxalate transport in the PH1 mouse model are associated with a normalization of plasma oxalate and urinary oxalate excretion in otherwise hyperoxalemic and hyperoxaluric animals. PMID:21163900

Blood plasma response and urinary excretion of nitrite and nitrate in milk-fed calves after oral nitrite and nitrate administration.

PubMed

Hüsler, B R.; Blum, J W.

2001-05-01

There is marked endogenous production of nitrate in young calves. Here we have studied the contribution of exogenous nitrate and nitrite to plasma concentrations and urinary excretion of nitrite and nitrate in milk-fed calves. In experiment 1, calves were fed 0 or 200 &mgr;mol nitrate or nitrite/kg(0.75) or 100 &mgr;mol nitrite plus 100 &mgr;mol nitrate/kg(0.75) with milk for 3 d. In experiment 2, calves were fed 400 &mgr;mol nitrate or nitrite/kg(0.75) with milk for 1 d. Plasma nitrate rapidly and comparably increased after feeding nitrite, nitrate or nitrite plus nitrate. The rise of plasma nitrate was greater if 400 than 200 &mgr;mol nitrate or nitrite/kg(0.75) were fed. Plasma nitrate decreased slowly after the 3-d administration of 200 &mgr;mol nitrate or nitrite/kg(0.75) and reached pre-experimental concentrations 4 d later. Urinary nitrate excretions nearly identically increased if nitrate, nitrite or nitrite plus nitrate were administered and excreted amounts were greater if 400 than 200 &mgr;mol nitrate or nitrite/kg(0.75) were fed. After nitrite ingestion plasma nitrite only transiently increased after 2 and 4 h and urinary excretion rates remained unchanged. Plasma nitrate concentration remained unchanged if milk was not supplemented with nitrite or nitrate. Nitrate concentrations were stable for 24 h after addition of nitrite to full blood in vitro, whereas nitrite concentrations decreased within 2 h. In conclusion, plasma nitrate concentrations and urinary nitrate excretions are enhanced dose-dependently by feeding low amounts of nitrate and nitrite, whereas after ingested nitrite only a transient and small rise of plasma nitrite is observed because of rapid conversion to nitrate.

Triiodothyronine and thyroxine in urine. I. Measurement and application.

PubMed

Shakespear, R A; Burke, C W

1976-03-01

Urinary triiodothyronine (T3) and thyroxine (T4) were measured by RIA, and T4 was also measured by competitive protein binding (CPB). pH 1-hydrolysable conjugates were 48% of total urinary T3, and enzyme- or pH 1-hydrolysable conjugates were 55% and 61% of total urinary T4. The mean unconjugated T3 excretion was 34.3 ng/h (0.99 mug T3/g creatinine) in normal subjects (no day-night rhythm found), 1.56 mug/g in late pregnancy, 0.82 mug/g in neonates (1-12 days), and was also unchanged in persons with high or low thyroxine-binding globulin (TBG). In thyrotoxicosis, mean T3 excretion was 281 ng/h, no values being in the normal range. In primary hypothyroidism it was 18.3 ng/h, but over half the values were in the normal range. The mean urinary unconjugated T4 was 82.2 ng/h (1.37 mug T4/g creatinine) in normal subjects, 1.6 mug/g in neonates, and unchanged in persons with high or low TBG, except that in pregnancy high values were compatible with increases protein excretion. Apparently increased day-time T4 excretion compared with night-time excretion may also be due to changes in protein excretion rate. The mean T4 in thyrotoxicosis was 337 ng/h (12% of values in the normal range) and 32.8 ng/h in primary hypothyroidism (over half the normal range). All the assays, especially that of T4 by CPB gave readings which were incorrect with protein concentrations above 100 mg/l. Urinary T3 and T4 assays for clinical purposes have few practical advantages over serum assays, despite the relationship of urine T3 and T4 to serum unbound levels.

Demographic, dietary, and urinary factors and 24-h urinary calcium excretion.

PubMed

Taylor, Eric N; Curhan, Gary C

2009-12-01

Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values < or =0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend < or =0.01). Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.

Polyethylene glycol versus dual sugar assay for gastrointestinal permeability analysis: is it time to choose?

PubMed Central

van Wijck, Kim; Bessems, Babs AFM; van Eijk, Hans MH; Buurman, Wim A; Dejong, Cornelis HC; Lenaerts, Kaatje

2012-01-01

Background Increased intestinal permeability is an important measure of disease activity and prognosis. Currently, many permeability tests are available and no consensus has been reached as to which test is most suitable. The aim of this study was to compare urinary probe excretion and accuracy of a polyethylene glycol (PEG) assay and dual sugar assay in a double-blinded crossover study to evaluate probe excretion and the accuracy of both tests. Methods Gastrointestinal permeability was measured in nine volunteers using PEG 400, PEG 1500, and PEG 3350 or lactulose-rhamnose. On 4 separate days, permeability was analyzed after oral intake of placebo or indomethacin, a drug known to increase intestinal permeability. Plasma intestinal fatty acid binding protein and calprotectin levels were determined to verify compromised intestinal integrity after indomethacin consumption. Urinary samples were collected at baseline, hourly up to 5 hours after probe intake, and between 5 and 24 hours. Urinary excretion of PEG and sugars was determined using high-pressure liquid chromatography-evaporative light scattering detection and liquid chromatography-mass spectrometry, respectively. Results Intake of indomethacin increased plasma intestinal fatty acid-binding protein and calprotectin levels, reflecting loss of intestinal integrity and inflammation. In this state of indomethacin-induced gastrointestinal compromise, urinary excretion of the three PEG probes and lactulose increased compared with placebo. Urinary PEG 400 excretion, the PEG 3350/PEG 400 ratio, and the lactulose/rhamnose ratio could accurately detect indomethacin-induced increases in gastrointestinal permeability, especially within 2 hours of probe intake. Conclusion Hourly urinary excretion and diagnostic accuracy of PEG and sugar probes show high concordance for detection of indomethacin-induced increases in gastrointestinal permeability. This comparative study improves our knowledge of permeability analysis in man by providing a clear overview of both tests and demonstrates equivalent performance in the current setting. PMID:22888267

Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

PubMed Central

Fernández-Repollet, E; Martínez-Maldonado, M; Opava-Stitzer, S

1980-01-01

1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic condition. PMID:7441565

Influence of injected caffeine on the metabolism of calcium and the retention and excretion of sodium, potassium, phosphorus, magnesium, zinc and copper in rats.

PubMed

Yeh, J K; Aloia, J F; Semla, H M; Chen, S Y

1986-02-01

Mineral metabolism was studied by the metabolic balance technique in rats with and without administration of caffeine. Caffeine was injected subcutaneously each day at either 2.5 mg or 10 mg/100 g body weight for 2 wk before the balance studies. Urinary volume excretion was higher in the group given caffeine than in the control group, but the creatinine clearance was not different. Urinary excretion of potassium, sodium, inorganic phosphate, magnesium and calcium, but not of zinc and copper, was also higher in the rats given caffeine. The rank order of the difference was the same as the percent of ingested mineral excreted in urine in the absence of caffeine. Caffeine caused a negative balance of potassium, sodium and inorganic phosphate. There was no significant difference from the control levels and in the apparent metabolic balance of calcium and magnesium. The urinary and fecal excretion of zinc and copper were found to be unaffected by caffeine. It is suggested that chronic administration of caffeine may lead to a tendency toward deficiency of those minerals that are excreted primarily in urine.

Evaluation of the process of recycling and renal parenchymal injury after eswl with metabolites excreted in the urine.

PubMed

Ceylan, Cavit; Dogan, Serkan; Saydam, Gulsevim; Kocak, Mehmet Zait; Doluoglu, Omer Gokhan

2013-01-01

To show renal parenchymal injury depending on extracorporeal shock wave lithotripsy (ESWL). The patients with one renal stone and in whom ESWL is planned among the patients in whom renal stone was determined. Their 24-h urine samples were collected just before and after the ESWL treatment. Cit (citrate), UrA (uric acid), RBP (retinol-binding protein), NAG (N-acetyl-β-Đ-glucosaminidase), Cr (creatinine), Na (sodium), K (potassium), P (phosphor), Ca (calcium), and Cl (chlorine) metabolites excreted in urine were evaluated after urine samples were taken on the study day. Changes in the metabolites excreted; the number, frequency, and duration of ESWL shock wave; the energy; and the body mass index were recorded. The results for p < 0.05 will be accepted as statistically significant. Two sessions of ESWL were applied to a total of 20 patients. When metabolites excreted in the urine before (B1E) and after (A1E) the first session of ESWL, and before (B2E) and after (A2E) the second session of ESWL, were evaluated, no statistically significant result for Ca and Cl excretion was noted. For NAG and Cr, a significant difference was observed in terms of metabolite excretion between B1E and B2E. For other metabolites, we saw that there is no difference between B1E and B2E. While a significant metabolite change was observed for RBP, NAG, Cr, and Na as long as A1E and A2E ESWL session number increases, other metabolites were not significant. Shock waves induce significant damage to the renal and adjacent tissues as indicated by a significant increase in cell-escaped enzymes and electrolytes and the extent of damage depends on the energy and the number of shock wave exposure.

Effect of age on toxicokinetics among human volunteers exposed to propylene glycol methyl ether (PGME).

PubMed

Hopf, Nancy B; Vernez, David; Berthet, Aurelie; Charriere, Nicole; Arnoux, Christine; Tomicic, Catherine

2012-05-20

Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults biologically respond to pollutants. In a controlled human toxicokinetic study (exposure chamber; 12 m³), aging volunteers (n=10; >58 years) were exposed to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h. The dose-dependent renal excretion of oxidative metabolites, conjugated and free PGME could potentially be altered by age. (1) Compare PGME toxicokinetic profiles between aging and young volunteers (20-25 years) and gender; (2) test the predictive power of a compartmental toxicokinetic (TK) model developed for aging persons against urinary PGME concentrations found in this study. Urine samples were collected before, during, and after the exposure. Urinary PGME was quantified by capillary GC/FID. Differences in urinary PGME profiles were not noted between genders but between age groups. Metabolic parameters had to be changed to fit the age adjusted TK model to the experimental results, implying a slower enzymatic pathway in the aging volunteers. For an appropriate exposure assessment, urinary total PGME should be quantified. Age is a factor that should be considered when biological limit values are developed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Determination of urinary concentrations of pseudoephedrine and cathine after therapeutic administration of pseudoephedrine-containing medications to healthy subjects: implications for doping control analysis of these stimulants banned in sport.

PubMed

Barroso, Osquel; Goudreault, Danielle; Carbó Banús, Marcel-lí; Ayotte, Christiane; Mazzoni, Irene; Boghosian, Thierry; Rabin, Olivier

2012-05-01

Due to its stimulatory effects on the central nervous system, and its structural similarity to banned stimulants such as ephedrine and methamphetamine, pseudoephedrine (PSE) at high doses is considered as an ergogenic aid for boosting athletic performance. However, the status of PSE in the International Standard of the Prohibited List as established under the World Anti-Doping Code has changed over the years, being prohibited until 2003 at a urinary cut-off value of 25 µg/ml, and then subsequently removed from the Prohibited List during the period 2004-2009. The re-consideration of this position by the World Anti-Doping Agency (WADA) List Expert Group has led to the reintroduction of PSE in the Prohibited List in 2010. In this manuscript, we present the results of two WADA-sponsored clinical studies on the urinary excretion of PSE and its metabolite cathine (CATH) following the oral administration of different PSE formulations to healthy individuals at therapeutic regimes. On this basis, the current analytical urinary threshold for the detection of PSE as a doping agent in sport has been conservatively established at 150 µg/ml Copyright © 2011 John Wiley & Sons, Ltd.

[Validity of the assessment of urinary protein excretion by spot urine in patients with chronic kidney disease].

PubMed

Hayashi, Ami; Okada, Tomonari; Matsumoto, Hiroshi; Nagaoka, Yume; Wada, Toshikazu; Gondo, Asako; Nango, Tomoka; Miyaoka, Yoshitaka; Watanabe, Kanna; Iwata, Azusa; Nakao, Toshiyuki

2013-01-01

We investigate the validity of the assessment of urinary protein excretion by spot urine samples collected by different methods in outpatients with chronic kidney disease (CKD). SUBJECTS AND METHODS We obtained 24-hour urine and two spot urine samples, including the first morning urine and daytime urine in 159 CKD patients. Urinary protein excretion was assessed by the protein/creatinine ratio from spot urine samples (morning: m-UP (g/gCr), daytime: d-UP (g/gCr) ]. We examined the correlations and the differences among m-UP, d-UP and the actual urinary protein excretion obtained by 24-hour urine (a-UP(g/day) . Significant correlations were found between m-UP and a-UP, and between d-UP and a-UP (r = 0.88, 0.85; p < 0.001). Correlations between m-UP and a-UP were greater relative to those between d-UP and a-UP in patients with less than 3.5 g/day of a-UP and in patients with CKD stages 1 to approximately 3. The percent difference between m-UP and a-UP was--16.0 +/- 40.5%, and that between d-UP and a-UP was 27.1 +/- 72.9%. The absolute value of the percent difference between d-UP and a-UP tended to be greater than that between m-UP and a-UP (34.9 +/- 25.9% vs. 49.9 +/- 59.9%, p = 0.06). Urinary protein/creatinie ratio of the first morning urine is better approximate the urinary protein excretion obtained by 24-hour urine compared with that of spot urine in the daytime.

Urinary free cortisol and cortisone excretion in healthy individuals: influence of water loading.

PubMed

Fenske, Martin

2006-11-01

The influence of water loading on urinary excretion of free cortisol and cortisone was investigated in healthy men. The results were as follows: water loading tests (intake of 0.25-1.5 L) in a single individual showed that a water load of 1.5 L reliably increased the excretion of urine, free cortisol and cortisone (p < 0.01). Regression analyses gave significant correlations of urine volume with free cortisol and free cortisone, and of free cortisol and free cortisone. Corresponding results were obtained when water loading tests were performed in males who ingested 1.5 L of water (n = 8): the excretion of urine, free cortisol and free cortisone were significantly augmented; correlated was urine volume with free cortisol and free cortisone, and free cortisol with free cortisone. In a third set of tests, volunteers collected one 5 h urine (10:00-15:00 h) after the intake of 3 x 0.1 or 0.5 L at 11:00, 12:00 and 14:00 h. Excretion of urine, free cortisol and free cortisone in males of the low water loading group (3 x 0.1 L) was 0.59 mL/min, and 8.2 or 15.0 microg/5 h; corresponding values in individuals ingesting 3 x 0.5 L of water were 1.5 mL/min (p < 0.01), 12.3 microg/5 h (p > 0.05) and 26.3 microg/5 h (p < 0.02). In summary, urinary free cortisol and cortisone excretion in healthy men depends on urine volume, especially during water diuresis. Thus, interpretation of free cortisol and especially of free cortisone excretion is only possible if subjects strictly control their fluid intake and if urine volume is considered an important pre-analytical parameter-otherwise, interpretation of urinary free cortisol results is difficult and of urinary free cortisone data remains tenuous at best.

N-Acetyl-S-(n-Propyl)-L-Cysteine in Urine from Workers Exposed to 1-Bromopropane in Foam Cushion Spray Adhesives

PubMed Central

Hanley, Kevin W.; Petersen, Martin R.; Cheever, Kenneth L.; Luo, Lian

2009-01-01

1-Bromopropane (1-BP) has been marketed as an alternative for ozone depleting and other solvents; it is used in aerosol products, adhesives, metal, precision, and electronics cleaning solvents. Mechanisms of toxicity of 1-BP are not fully understood, but it may be a neurological and reproductive toxicant. Sparse exposure information prompted this study using 1-BP air sampling and urinary metabolites. Mercapturic acid conjugates are excreted in urine from 1-BP metabolism involving debromination. Research objectives were to evaluate the utility of urinary N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) for assessing exposure to 1-BP and compare it to urinary bromide [Br(−)] previously reported for these workers. Forty-eight-hour urine specimens were obtained from 30 workers at two factories where 1-BP spray adhesives were used to construct polyurethane foam seat cushions. Urine specimens were also obtained from 21 unexposed control subjects. All the workers' urine was collected into composite samples representing three time intervals: at work, after work but before bedtime, and upon awakening. Time-weighted average (TWA) geometric mean breathing zone concentrations were 92.4 and 10.5 p.p.m. for spraying and non-spraying jobs, respectively. Urinary AcPrCys showed the same trend as TWA exposures to 1-BP: higher levels were observed for sprayers. Associations of AcPrCys concentrations, adjusted for creatinine, with 1-BP TWA exposure were statistically significant for both sprayers (P < 0.05) and non-sprayers (P < 0.01). Spearman correlation coefficients for AcPrCys and Br(−) analyses determined from the same urine specimens were highly correlated (P < 0.0001). This study confirms that urinary AcPrCys is an important 1-BP metabolite and an effective biomarker for highly exposed foam cushion workers. PMID:19706636

Influence of genetic susceptibility on the urinary excretion of 8-hydroxydeoxyguanosine of firefighters.

PubMed

Hong, Y C; Park, H S; Ha, E H

2000-06-01

Oxidative DNA damage has been implicated in carcinogenesis. The DNA damage can be assessed from the urinary excretion of the DNA-repair product 8-hydroxydeoxyguanosine (8-OH-dG). The factors were investigated that influenced the excretion of urinary 8-OH-dG in 78 firefighters. 53 Out of 78 firefighters were exposed to fire within 5 days of the study and 25 were not. 8-OH-dG was measured by ELISA and the distribution of the genotypes of CYP1A1, CYP2E1, GSTM1, and GSTT1 was measured by polymerase chain reaction. The homozygous wild type frequencies of CYP1A1 MspI, CYP1A1 ile-val, CYP2E1, GSTM1, and GSTT1 were 31.5%, 56.2%, 60.3%, 50.7%, and 53.4%, respectively. The geometric mean of urinary 8-OH-dG was 14.1 ng/mg creatinine in more active firefighters and 12.3 ng/mg creatinine in non-exposed and less active subjects. Significantly increased concentrations of urinary 8-OH-dG were found to be associated with cigarette smoking, and 14% of the variation of 8-OH-dG was explained by cigarettes smoked per day. The CYP1A1 MspI, CYP1A1 ile-val, GSTM1, and GSTT1 genetic polymorphisms were not found to be significantly associated with the urinary excretion of 8-OH-dG. However, the subjects carrying the CYP2E1 mutant type excreted higher concentrations of 8-OH-dG and there was a marginally significant interaction of GSTT1 with firefighting activity. Multiple regression analysis confirmed that smoking was the strongest predictor of excretion of 8-OH-dG. Age, body mass index, and firefighting activity were not significant predictive factors for urinary 8-OH-dG. Smoking and CYP2E1 gene polymorphism may be important factors in carcinogenesis and the GSTT1 positive genotype may be a genetic susceptibility factor in firefighters who are exposed regularly to various chemical carcinogens.

Effects of clofibrate and indocyanine green on the hepatobiliary disposition of acetaminophen and its metabolites in male CD-1 mice.

PubMed

Chen, C; Hennig, G E; McCann, D J; Manautou, J E

2000-11-01

1. The effects of clofibrate (CFB) and indocyanine green (ICG) on the biliary excretion of acetaminophen (APAP) and its metabolites were investigated. 2. Male CD-1 mice were pretreated with 500 mg CFB/kg, i.p. for 10 days. Controls received corn oil vehicle only. After overnight fasting, common bile duct-cannulated mice were challenged with a non-toxic dose of APAP (1 mmol/kg, i.v.). 3. CFB pretreatment did not affect bile flow rate, nor did it affect the cumulative biliary excretion of APAP and its conjugated metabolites. 4. Additional CFB or corn oil pretreated mice were given 30 mumol indocyanine green (ICG)/kg, i.v., immediately before APAP dosing. ICG is a non-metabolizable organic anion that is completely excreted into the bile through a canalicular transport process for organic anions. 5. ICG significantly decreased the bile flow rate and biliary concentration of APAP-glutathione, APAP-glucuronide and APAP-mercapturate within the first hour after dosing without affecting the biliary concentration of APAP. 6. The results indicate that CFB pretreatment does not affect the total amount of APAP and its metabolites excreted in bile. They also suggest that the biliary excretion of several conjugated metabolites of APAP share the same excretory pathway with the organic anion ICG.

Metabolism of pentachlorophenol by fish

USGS Publications Warehouse

Stehly, G.R.; Hayton, W.L.

1989-01-01

Interspecies variability in the metabolism of pentachlorophenol (PCP) was investigated by exposing rainbow trout, fathead minnows, sheepshead minnow, firemouth, and goldfish to water-borne super(14)C-PCP for 64 h. The amounts of metabolites in bile and exposure water were species-dependent; all of the metabolites excreted into the water were sulphate conjugates while bile was enriched in glucuronide conjugates. Biliary excretion accounted for less than 30% of the total PCP metabolites. Biliary metabolites alone were a poor indication of the metabolites produced and of the major routes of elimination.

Urinary purine derivatives as a tool to estimate dry matter intake in cattle: a meta-analysis

USDA-ARS?s Scientific Manuscript database

The objectives of this study were: 1) to investigate the relationship between dry matter intake (DMI) and urinary purine derivatives (PD) excretion in order to develop equations to predict DMI, and 2) to determine the endogenous excretion of PD for beef and dairy cattle using a meta-analytic approac...

Increased leukotriene E4 excretion in systemic mastocytosis.

PubMed

Butterfield, Joseph H

2010-06-01

Cysteinyl leukotrienes such as LTE(4) are produced by mast cells, neutrophils, eosinophils, and macrophages. LTE(4) levels have not been reported in systemic mastocytosis, a disorder with a large increase in mast cell numbers. Urinary LTE(4) from patients referred for symptoms potentially due to mast cell degranulation or systemic mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. The diagnosis of systemic mastocytosis was established using current World Health Organization criteria. Compared with a control group of patients with various potential mast cell-related symptoms (e.g., "spells"), patients with systemic mastocytosis had a significant (P=.01) increase in urinary LTE(4) excretion, whether expressed as LTE(4) ng/g creatinine or as LTE(4) ng/24h. There was a moderate correlation of LTE(4) ng/24h with excretion of N-methyl histamine and serum tryptase but not with urinary 11beta-prostaglandin F(2alpha) (11beta-PGF(2alpha)) excretion. LTE(4) excretion is increased in patients with systemic mastocytosis and potentially contributes to clinical symptoms. Copyright 2010 Elsevier Inc. All rights reserved.

Favipiravir inhibits acetaminophen sulfate formation but minimally affects systemic pharmacokinetics of acetaminophen

PubMed Central

Zhao, Yanli; Harmatz, Jerold S; Epstein, Carol R; Nakagawa, Yukako; Kurosaki, Chie; Nakamura, Tetsuro; Kadota, Takumi; Giesing, Dennis; Court, Michael H; Greenblatt, David J

2015-01-01

Aims The antiviral agent favipiravir is likely to be co-prescribed with acetaminophen (paracetamol). The present study evaluated the possiblility of a pharmacokinetic interaction between favipiravir and acetaminophen, in vitro and in vivo. Methods The effect of favipivir on the transformation of acetaminophen to its glucuronide and sulfate metabolites was studied using a pooled human hepatic S9 fraction in vitro. The effect of acute and extended adminstration of favipiravir on the pharmacokinetics of acetaminophen and metabolites was evaluated in human volunteers. Results Favipiravir inhibited the in vitro formation of acetaminophen sulfate, but not acetaminophen glucuronide. In human volunteers, both acute (1 day) and extended (6 days) administration of favipiravir slightly but significantly increased (by about 20 %) systemic exposure to acetaminophen (total AUC), whereas Cmax was not significantly changed. AUC for acetaminophen glucuronide was increased by 23 to 35 % above control by favipiravir, while AUC for acetaminophen sulfate was reduced by about 20 % compared to control. Urinary excretion of acetaminophen sulfate was likewise reduced to 44 to 65 % of control values during favipiravir co-administration, while excretion of acetaminophen glucuronide increased to 17 to 32 % above control. Conclusion Favipiravir inhibits acetaminophen sulfate formation in vitro and in vivo. However the increase in systemic exposure to acetaminophen due to favipiravir co-administration, though statistically significant, is small in magnitude and unlikely to be of clinical importance. PMID:25808818

Metabolism and excretion of 2-ethoxyethanol in the adult male rat.

PubMed Central

Cheever, K L; Plotnick, H B; Richards, D E; Weigel, W W

1984-01-01

The routes of 14C excretion following the administration of a single oral 230 mg/kg body weight dose of 2-ethoxyethanol [ethanol-1,2-14C] or 2-ethoxyethanol [ethoxy-1-14C] to male Sprague-Dawley rats were investigated. Elimination of the 14C by the urinary route accounted for 76 to 80% of the dose within 96 hr. The main pathway of biotransformation is oxidation to the corresponding acid, with some subsequent conjugation of the acid metabolite with glycine. The major metabolites, ethoxyacetic acid and N-ethoxy-acetyl glycine, representing 73 to 76% of the administered dose, were eliminated in the urine. The major difference in the metabolic profiles of the two radiochemicals was in the rate and amount of 14CO2 expired via the lung. Of the administered 14C, 11.7% of the ethoxy-labeled and 4.6% of the ethanol-labeled compounds were eliminated as CO2. The biological half-time was 9.9 +/- 1.5 hr for the ethoxy-labeled compound and 12.5 +/- 1.9 hr for the ethanol label. After administration of the ethanol-labeled compound, the only radiolabeled component found in the rat testes was identified as ethoxyacetic acid. Results of this study suggest that the reported testicular effects in the rat may be a result of tissue levels of ethoxyacetic acid. PMID:6437805

Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis.

PubMed

Bagger, Yu Z; Tankó, László B; Alexandersen, Peter; Karsdal, Morten A; Olson, Melvin; Mindeholm, Linda; Azria, Moïse; Christiansen, Claus

2005-09-01

To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the baseline level of cartilage turnover. This was a randomized, double blind, placebo-controlled clinical setting including 152 Danish postmenopausal women aged 55-85. The subjects received treatment with the different doses of sCT (0.15, 0.4, 1.0, or 2.5 mg) combined with Eligen technology-based carrier molecule (200 mg), or placebo for 3 months. The efficacy parameter was the changes in the 24-h excretion of urinary CTX-I/II corrected for creatinine excretion at month 3. sCT induced a significant dose-dependent decrease in 24-h urinary CTX-II excretion. Similar dose-dependent responses were found in 24-h urinary CTX-I. When stratifying the study population into tertiles of baseline urinary CTX-II, the present osteoarthritic symptoms and definite cases of osteoarthritis (OA) were significantly more frequent in women in the highest tertile of CTX-II (mean 391 +/- 18 ng/mmol). Women who received 1.0 mg of sCT and had the highest cartilage turnover presented the greatest decrease in urinary CTX-II after 3 months of treatment. In addition to its pronounced effect on bone resorption, this novel oral sCT formulation may also reduce cartilage degradation and thereby provide therapeutic benefit in terms of chondroprotection. Women with high cartilage turnover are more likely to benefit from oral sCT treatment.

Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis.

PubMed

McGuire, Brendan M; Zupanets, Igor A; Lowe, Mark E; Xiao, Xunjun; Syplyviy, Vasyliy A; Monteleone, Jon; Gargosky, Sharron; Dickinson, Klara; Martinez, Antonia; Mokhtarani, Masoud; Scharschmidt, Bruce F

2010-06-01

Phenylbutyric acid (PBA), which is approved for treatment of urea cycle disorders (UCDs) as sodium phenylbutyrate (NaPBA), mediates waste nitrogen excretion via combination of PBA-derived phenylacetic acid with glutamine to form phenylactylglutamine (PAGN) that is excreted in urine. Glycerol phenylbutyrate (GPB), a liquid triglyceride pro-drug of PBA, containing no sodium and having favorable palatability, is being studied for treatment of hepatic encephalopathy (HE). In vitro and clinical studies have been performed to assess GPB digestion, safety, and pharmacology in healthy adults and individuals with cirrhosis. GPB hydrolysis was measured in vitro by way of pH titration. Twenty-four healthy adults underwent single-dose administration of GPB and NaPBA and eight healthy adults and 24 cirrhotic subjects underwent single-day and multiple-day dosing of GPB, with metabolites measured in blood and urine. Simulations were performed to assess GPB dosing at higher levels. GPB was hydrolyzed by human pancreatic triglyceride lipase, pancreatic lipase-related protein 2, and carboxyl-ester lipase. Clinical safety was satisfactory. Compared with NaPBA, peak metabolite blood levels with GPB occurred later and were lower; urinary PAGN excretion was similar but took longer. Steady state was achieved within 4 days for both NaPBA and GPB; intact GPB was not detected in blood or urine. Cirrhotic subjects converted GPB to PAGN similarly to healthy adults. Simulations suggest that GPB can be administered safely to cirrhotic subjects at levels equivalent to the highest approved NaPBA dose for UCDs. GPB exhibits delayed release characteristics, presumably reflecting gradual PBA release by pancreatic lipases, and is well tolerated in adults with cirrhosis, suggesting that further clinical testing for HE is warranted.

Pharmacology and Safety of Glycerol Phenylbutyrate in Healthy Adults and Adults with Cirrhosis

PubMed Central

MCGuire, Brendan M.; Zupanets, Igor A.; Lowe, Mark E.; Xiao, Xunjun; Syplyviy, Vasyliy A.; Monteleone, Jon; Gargosky, Sharron; Dickinson, Klara; Martinez, Antonia; Mokhtarani, Masoud; Scharschmidt, Bruce F.

2013-01-01

Phenylbutyric acid (PBA), which is approved for treatment of urea cycle disorders (UCDs) as sodium phenylbutyrate (NaPBA), mediates waste nitrogen excretion via combination of PBA-derived phenylacetic acid with glutamine to form phenylactylglutamine (PAGN) that is excreted in urine. Glycerol phenylbutyrate (GPB), a liquid triglyceride pro-drug of PBA, containing no sodium and having favorable palatability, is being studied for treatment of hepatic encephalopathy (HE). In vitro and clinical studies have been performed to assess GPB digestion, safety, and pharmacology in healthy adults and individuals with cirrhosis. GPB hydrolysis was measured in vitro by way of pH titration. Twenty-four healthy adults underwent single-dose administration of GPB and NaPBA and eight healthy adults and 24 cirrhotic subjects underwent single-day and multiple-day dosing of GPB, with metabolites measured in blood and urine. Simulations were performed to assess GPB dosing at higher levels. GPB was hydrolyzed by human pancreatic triglyceride lipase, pancreatic lipase-related protein 2, and carboxyl-ester lipase. Clinical safety was satisfactory. Compared with NaPBA, peak metabolite blood levels with GPB occurred later and were lower; urinary PAGN excretion was similar but took longer. Steady state was achieved within 4 days for both NaPBA and GPB; intact GPB was not detected in blood or urine. Cirrhotic subjects converted GPB to PAGN similarly to healthy adults. Simulations suggest that GPB can be administered safely to cirrhotic subjects at levels equivalent to the highest approved NaPBA dose for UCDs. Conclusion GPB exhibits delayed release characteristics, presumably reflecting gradual PBA release by pancreatic lipases, and is well tolerated in adults with cirrhosis, suggesting that further clinical testing for HE is warranted. PMID:20512995

Estimation of the 24-h urinary protein excretion based on the estimated urinary creatinine output.

PubMed

Ubukata, Masamitsu; Takei, Takashi; Nitta, Kosaku

2016-06-01

The urinary protein/creatinine ratio [Up/Ucr (g/gCr)] has been used in the clinical management of patients with chronic kidney disease (CKD). However, a discrepancy is often noted between the Up/Ucr and 24-h urinary protein excretion [24hUp (g/day)] in patients with extremes of muscle mass. We examined devised a method for precise estimation of the 24-h urinary protein excretion (E-24hUp) based on estimation of 24-h urinary creatinine output (E-24hCr). Three parameters, spot Up/Ucr, 24hUP and E-24hUp (=Up/Ucr × E-24hCr), were determined in 116 adult patients with CKD. The correlations among the groups were analyzed. There was a significant correlation between the Up/Ucr and 24hUp (p < 0.001). We divided the patients into three groups according to the 24hUp; the low urinary protein group (<1.0 g/day), the intermediate urinary protein group (1.0-3.5 g/day), and the high urinary protein group (>3.5 g/day). There was a significant correlation between the Up/Ucr and 24hUp in the low (p = 0.04) and high urinary protein (p = 0.01) groups, whereas the correlation coefficient was lower in the intermediate urinary protein (p = 0.07) group. Thus, we found a significant correlation between 24hUp and E-24hUp in the study population overall (p < 0.001), in the low (p = 0.01), in the intermediate (p < 0.001), and in the high urinary protein group (p < 0.001). We conclude that a poor correlation exists between the Up/Ucr and 24hUp in patients with intermediate urinary protein excretion levels. The recommended parameter for monitoring proteinuria in such patients may be the E-24hUp, which is calculated using the E-24hCr.

Reproductive physiology and development of artificial insemination technology in killer whales (Orcinus orca).

PubMed

Robeck, T R; Steinman, K J; Gearhart, S; Reidarson, T R; McBain, J F; Monfort, S L

2004-08-01

Research was conducted to define the basic reproductive physiology of killer whales (Orcinus orca) and to use this knowledge to facilitate the development of artificial insemination procedures. The specific objectives were 1) to determine the excretory dynamics of urinary LH and ovarian steroid metabolites during the estrous cycle; 2) to evaluate the effect of an exogenously administered, synthetic progesterone analog on reproductive hormone excretion; 3) to validate the use of transabdominal ultrasound for ovarian evaluation and timing of ovulation; 4) to examine the quality of semen after liquid storage and cryopreservation; and 5) to develop an intrauterine insemination technique. Based on urinary endocrine monitoring of 41 follicular phases and 26 complete cycles from five females, estrous cycles were 41 days long and comprised a 17-day follicular phase and a 21-day luteal phase. A consistent temporal relationship was observed between peak estrogen conjugates and the LH surge, the latter of which occurred approximately 0.5 days later. Two animals placed on oral altrenogest (three separate occasions for 30, 17, and 31 days, respectively) excreted peak urinary estrogen concentrations 25 days after withdrawal that were followed by sustained elevations in urinary pregnanediol-3alpha-glucuronide excretion. Mean preovulatory follicle diameter was 3.9 cm (n = 6), and ovulation occurred 38 h (n = 5) after the peak of the LH surge. Based on visual estimates of motility, liquid-stored semen maintained 92% of its raw ejaculate sperm motility index (total progressive motility x kinetic rating [0-5 scale, where 0 = no movement and 5 = rapid progressive movement]) when held at 4 degrees C for 3 days postcollection. Semen cryopreserved using a medium freezing rate demonstrated good postthaw total motility (50%), progressive motility (94%), and kinetic rating (3.5). Insemination during eight estrous cycles resulted in three pregnancies (38%), two from liquid-stored and one from cryopreserved semen. Two calves were delivered after gestation lengths of 552 and 554 days, respectively. These data demonstrate the potential of noninvasive endocrine monitoring combined with serial ultrasonography to improve our understanding of the reproductive biology of cetaceans. This fundamental knowledge was essential for ensuring the first successful conceptions, resulting in live offspring, using artificial insemination in any cetacean species.

Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation.

PubMed

Goudarzi, Maryam; Chauthe, Siddheshwar; Strawn, Steven J; Weber, Waylon M; Brenner, David J; Fornace, Albert J

2016-05-20

With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; external γ irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 ((137)Cs) and Strontium-90 ((90)Sr). The multiple reaction monitoring analysis showed that, while exposure to (137)Cs and (90)Sr induced a statistically significant and persistent decrease, similar doses of external γ beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to (90)Sr and (137)Cs and to external γ beam radiation.

Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation

PubMed Central

Goudarzi, Maryam; Chauthe, Siddheshwar; Strawn, Steven J.; Weber, Waylon M.; Brenner, David J.; Fornace, Albert J.

2016-01-01

With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs) and Strontium-90 (90Sr). The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation. PMID:27213362

Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in High-Risk Elder Patients of Stroke from the Rural Areas of Shaanxi Province

PubMed Central

Ma, Wenxia; Yin, Xuejun; Zhang, Ruijuan; Liu, Furong; Yang, Danrong; Fan, Yameng; Rong, Jie; Tian, Maoyi; Yu, Yan

2017-01-01

Background: 24-h urine collection is regarded as the “gold standard” for monitoring sodium intake at the population level, but ensuring high quality urine samples is difficult to achieve. The Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT) and Tanaka methods have been used to estimate 24-h urinary sodium excretion from spot urine samples in some countries, but few studies have been performed to compare and validate these methods in the Chinese population. Objective: To compare and validate the Kawasaki, INTERSALT and Tanaka formulas in predicting 24-h urinary sodium excretion using spot urine samples in 365 high-risk elder patients of strokefrom the rural areas of Shaanxi province. Methods: Data were collected from a sub-sample of theSalt Substitute and Stroke Study. 365 high-risk elder patients of stroke from the rural areas of Shaanxi province participated and their spot and 24-h urine specimens were collected. The concentrations of sodium, potassium and creatinine in spot and 24-h urine samples wereanalysed. Estimated 24-h sodium excretion was predicted from spot urine concentration using the Kawasaki, INTERSALT, and Tanaka formulas. Pearson correlation coefficients and agreement by Bland-Altman method were computed for estimated and measured 24-h urinary sodium excretion. Results: The average 24-h urinary sodium excretion was 162.0 mmol/day, which representing a salt intake of 9.5 g/day. Three predictive equations had low correlation with the measured 24-h sodium excretion (r = 0.38, p < 0.01; ICC = 0.38, p < 0.01 for the Kawasaki; r = 0.35, p < 0.01; ICC = 0.31, p < 0.01 for the INTERSALT; r = 0.37, p < 0.01; ICC = 0.34, p < 0.01 for the Tanaka). Significant biases between estimated and measured 24-h sodium excretion were observed (all p < 0.01 for three methods). Among the three methods, the Kawasaki method was the least biased compared with the other two methods (mean bias: 31.90, 95% Cl: 23.84, 39.97). Overestimation occurred when the Kawasaki and Tanaka methods were used while the INTERSALT method underestimated 24-h sodium excretion. Conclusion: The Kawasaki, INTERSALT and Tanaka methods for estimation of 24-h urinary sodium excretion from spot urine specimens were inadequate for the assessment of sodium intake at the population level in high-risk elder patients of stroke from the rural areas of Shaanxi province, although the Kawasaki method was the least biased compared with the other two methods. PMID:29019912

Validation and Assessment of Three Methods to Estimate 24-h Urinary Sodium Excretion from Spot Urine Samples in High-Risk Elder Patients of Stroke from the Rural Areas of Shaanxi Province.

PubMed

Ma, Wenxia; Yin, Xuejun; Zhang, Ruijuan; Liu, Furong; Yang, Danrong; Fan, Yameng; Rong, Jie; Tian, Maoyi; Yu, Yan

2017-10-11

Background : 24-h urine collection is regarded as the "gold standard" for monitoring sodium intake at the population level, but ensuring high quality urine samples is difficult to achieve. The Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT) and Tanaka methods have been used to estimate 24-h urinary sodium excretion from spot urine samples in some countries, but few studies have been performed to compare and validate these methods in the Chinese population. Objective : To compare and validate the Kawasaki, INTERSALT and Tanaka formulas in predicting 24-h urinary sodium excretion using spot urine samples in 365 high-risk elder patients of strokefrom the rural areas of Shaanxi province. Methods : Data were collected from a sub-sample of theSalt Substitute and Stroke Study. 365 high-risk elder patients of stroke from the rural areas of Shaanxi province participated and their spot and 24-h urine specimens were collected. The concentrations of sodium, potassium and creatinine in spot and 24-h urine samples wereanalysed. Estimated 24-h sodium excretion was predicted from spot urine concentration using the Kawasaki, INTERSALT, and Tanaka formulas. Pearson correlation coefficients and agreement by Bland-Altman method were computed for estimated and measured 24-h urinary sodium excretion. Results : The average 24-h urinary sodium excretion was 162.0 mmol/day, which representing a salt intake of 9.5 g/day. Three predictive equations had low correlation with the measured 24-h sodium excretion (r = 0.38, p < 0.01; ICC = 0.38, p < 0.01 for the Kawasaki; r = 0.35, p < 0.01; ICC = 0.31, p < 0.01 for the INTERSALT; r = 0.37, p < 0.01; ICC = 0.34, p < 0.01 for the Tanaka). Significant biases between estimated and measured 24-h sodium excretion were observed (all p < 0.01 for three methods). Among the three methods, the Kawasaki method was the least biased compared with the other two methods (mean bias: 31.90, 95% Cl: 23.84, 39.97). Overestimation occurred when the Kawasaki and Tanaka methods were used while the INTERSALT method underestimated 24-h sodium excretion. Conclusion : The Kawasaki, INTERSALT and Tanaka methods for estimation of 24-h urinary sodium excretion from spot urine specimens were inadequate for the assessment of sodium intake at the population level in high-risk elder patients of stroke from the rural areas of Shaanxi province, although the Kawasaki method was the least biased compared with the other two methods.

Self-reports of salt intake by 10- to 18-year-olds: relationship to urinary sodium excretion.

PubMed

Murphy, J K; Alpert, B S; Stapleton, F B; Miller, L A; Willey, E S; Walker, S S; Nanney, G C

1990-03-01

Our data indicated that self-reports of consumption of salty foods by children and adolescents were associated with 24-hour urinary sodium excretion. Specifically, youths 10 to 18 years of age who selected a poster depicting high-sodium foods excreted significantly more sodium than youths who selected a poster depicting low-sodium foods. Future research is needed to refine simplified self-report measures, to corroborate the validity of the measures, and to extend the studies to other samples, e.g., younger children.

Effect of losartan on proteinuria and urinary angiotensinogen excretion in non-diabetic patients with chronic kidney disease.

PubMed

Lee, Yu-Ji; Cho, Seong; Kim, Sung Rok; Jang, Hye Ryoun; Lee, Jung Eun; Huh, Wooseong; Kim, Dae Joong; Oh, Ha Young; Kim, Yoon-Goo

2011-10-01

Activation of the rennin-angiotensin system (RAS) is thought to contribute to hypertension and proteinuria, and eventually to the progression of chronic kidney disease (CKD). Recent evidence suggests that urinary angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This study was performed to determine the effect of losartan on proteinuria and UAGT excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria. Thirty-two patients with non-nephrotic-range proteinuria (0.045-0.23 g/mmol creatinine) and normal renal function between April 2005 and April 2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in the losartan group received losartan 50 mg/day, and the doses were titrated up to 100 mg/day after 6 weeks. Serum and urinary angiotensinogen concentrations were measured by sandwich ELISA. The primary end point was the percentage change in proteinuria. The secondary end points were changes in estimated glomerular filtration rate and UAGT excretion. The follow-up period was 24 months. Baseline characteristics in the two groups were similar. After 24 months, losartan had reduced urinary protein excretion by 43% (from mean±SD 0.13±0.04 to 0.073±0.03 g/mmol, p<0.0001), but proteinuria had not changed in the control group. The percentage change in mean arterial pressure did not differ between the groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58±0.47 to 1.00±0.52, p=0.001). Estimated glomerular filtration rate decreased significantly only in the control group. Losartan significantly decreased proteinuria and UAGT excretion, and preserved renal function in non-diabetic patients with CKD.

Lime powder treatment reduces urinary excretion of total protein and transferrin but increases uromodulin excretion in patients with urolithiasis.

PubMed

Tosukhowong, Piyaratana; Kulpradit, Pimsuda; Chaiyarit, Sakdithep; Ungjareonwattana, Wattanachai; Kalpongnukul, Nuttiya; Ratchanon, Supoj; Thongboonkerd, Visith

2018-06-01

Our previous study has shown that lime powder (LP) had an inhibitory effect against calcium oxalate stone formation. However, the precise mechanisms underlying such beneficial effect remained unclear. Our present study thus aimed to address the effect of LP on excretory level and compositions of urinary proteins using a proteomics approach. From a total of 80 calcium oxalate stone formers recruited into our 2-year randomized clinical trial of LP effect, 10 patients with comparable age and clinical parameters were selected for this proteomic study. 24-h urine specimens were collected from all subjects, at baseline (before) and after LP treatment for 6 months, and then subjected to quantitative proteomics analysis and subsequent validation by ELISA. Total urinary protein excretion was significantly decreased by LP treatment, but unaffected by placebo. Nanoflow liquid chromatography coupled to tandem mass spectrometry (nanoLC-MS/MS) followed by quantitative analysis revealed 17 proteins whose levels were significantly altered (16 decreased and 1 increased) exclusively by LP treatment. Among these, the decrease of transferrin and increase of uromodulin were validated by ELISA. Moreover, there was a significant correlation between microalbuminuria and urinary transferrin level by Pearson's correlation test. In summary, LP treatment caused significant reduction in total urinary protein excretion and changes in urinary protein compositions that could be linked to stone inhibitory effects and might be relevant mechanisms responsible for the beneficial effects of LP to prevent kidney stone formation and recurrence.

[Renal handling of beta2 microglobulin. Its significance in carriers of adolescent nephronophthisis (NPH3)].

PubMed

Fernández, Carmen; Araque, Carolina; Méndez, Jorge; Angulo, Luisa; Fargier, Bernardo

2007-06-01

The adolescent nephronophthisis (NPH3) is a variant of the nephronophthisis. In Venezuela, one to three patients have been registered each year, all of them belonging to the same family tree. The objective of this study was to evaluate the function of the proximal convoluted tubule in NPHP3 carriers; using the beta2M as biological marker. Eight carriers, 7 heterozygotes and 1 homozygote, with normal renal function were compared with a 10 healthy subjects (control group). Serum beta2 microglobulin (beta2M), urinary beta2M, the quotient urinary beta2M/urinary creatinine and the beta2M fractional excretion were determinated. The filtered beta2M and the percentage of reabsortion were calculated. We observed an increase in the plasmatic concentration of beta2M but not related with a decrease of the glomerular filtration. The urinary beta2M, the beta2M/urinary creatinine relation and the fractional excretion of beta2M were normal. The filtered load of beta2M was elevated without increase in the excretion or percentage of reabsortion. We conclude that in our group of NPH3 carriers, functional changes in the proximal convoluted tubule, when measured by urinary excretion of beta2M, were absent. This finding suggests the existence of other mechanism of uptake or degradation of the substance in the proximal convoluted tubule, which have yet to be elucidated.

Demographic, Dietary, and Urinary Factors and 24-h Urinary Calcium Excretion

PubMed Central

Curhan, Gary C.

2009-01-01

Background and objectives: Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. Design, setting, participants, & measurements: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). Results: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values ≤0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend ≤0.01). Conclusions: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium. PMID:19820135

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

PubMed Central

Stroup, Bridget M.; Sawin, Emily A.; Murali, Sangita G.; Binkley, Neil; Hansen, Karen E.

2017-01-01

Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258. PMID:28546877

Urinary excretion of ciprofloxacin after administration of extended release tablets in healthy volunteers. Swellable drug-polyelectrolyte matrix versus bilayer tablets.

PubMed

Guzmán, M L; Romañuk, C B; Sanchez, M F; Luciani Giacobbe, L C; Alarcón-Ramirez, L P; Battistini, F D; Alovero, F L; Jimenez-Kairuz, A F; Manzo, R H; Olivera, María Eugenia

2018-02-01

This paper builds on a previous paper in which new ciprofloxacin extended-release tablets were developed based on a ciprofloxacin-based swellable drug polyelectrolyte matrix (SDPM-CIP). The matrix contains a molecular dispersion of ciprofloxacin ionically bonded to the acidic groups of carbomer, forming the polyelectrolyte-drug complex CB-CIP. This formulation showed that the release profile of the ciprofloxacin bilayer tablets currently commercialised can be achieved with a simpler strategy. Thus, since ciprofloxacin urine concentrations are associated with the clinical cure of urinary tract infections, the goal of this work was to compare the urinary excretion of SDPM-CIP tablets with those of the CIPRO XR® bilayer tablets. A batch of SDPM-CIP tablets was manufactured by the wet granulation method and the CB-CIP ionic complex was obtained in situ. Fasted healthy volunteers received a single oral dose of 500 mg ciprofloxacin of either formulation in a randomised crossover study. Urinary concentrations were assessed by HPLC at intervals up to 36 h. Pharmacokinetic parameters (rate of urinary excretion, maximum urine excretion rate, t max , area under the curve, amount and percentage of the ciprofloxacin dose excreted in urine) showed no statistical differences between both formulations at any of the time intervals of collection. The processing conditions to obtain SDPM-CIP tablets are easy to scale up since they involve technology currently employed in the pharmaceutical industry and the process is less challenging to implement. In addition, SDPM-CIP tablets met pharmacopoeial quality specifications.

Fate in humans of dietary intake of cyanogenic glycosides from roots of sweet cassava consumed in Cuba.

PubMed

Hernández, T; Lundquist, P; Oliveira, L; Pérez Cristiá, R; Rodriguez, E; Rosling, H

1995-01-01

We studied if consumption of boiled fresh roots from sweet cassava varieties grown in Cuba resulted in exposure to cyanogenic glycosides and their final breakdown product, cyanide. When adult, nonsmoking subjects consumed 1-4 kg cassava over 2 days, their urinary levels of the main cyanide metabolite, thiocyanate, only increased from a mean +/- SEM of 12 +/- 2 to 22 +/- 2 mumol/l, indicating a negligible cyanide exposure. Their mean urinary linamarin, the main cyanogenic glucoside in cassava, increased from 2 +/- 1 to 68 +/- 16 mumol/l. In a second experiment 5 subjects consumed one meal of 0.5 kg boiled cassava that contained 105 mumol linamarin and 8 mumol hydrogen cyanide (HCN). Quantitative urine collections prior to and after intake showed that 28% of linamarin was excreted during the following 24 hours, whereas a modest increase of urinary thiocyanate (SCN) only corresponded to the small amount of free HCN ingested. These results indicate that the dominant cyanogen in boiled cassava is glycosides that pass through the human body without causing cyanide exposure. It remains to be studied whether humans occasionally possess intestinal or tissue beta-glucosidases that can hydrolyse cyanogenic glycosides from cassava.

Absorption, Distribution, Metabolism, and Excretion of the Novel Helicase-Primase Inhibitor, Amenamevir (ASP2151), in Rodents.

PubMed

Ohtsu, Yoshiaki; Susaki, Yoko; Noguchi, Kiyoshi

2018-05-10

The helicase-primase inhibitor amenamevir (ASP2151) is a novel therapeutic agent which has been approved for the treatment of herpes zoster. The present study examined the pharmacokinetic profile of amenamevir in rodents and compared it with data from the literature of past and current established therapies (acyclovir and valaciclovir) to provide additional data to facilitate drug discovery and proper drug use. In situ absorption, blood and plasma radioactivity concentrations, tissue distribution, and excretion were determined using liquid scintillation counting. Plasma amenamevir concentrations were measured using a validated chromatographic method. Chemical structures of in vivo metabolites were investigated using liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Amenamevir, after single intravenous administration to mice, had an elimination half-life of 2 h. Bioavailability was 40% after single oral administration. In situ absorption data indicated that amenamevir is mainly absorbed in the small intestine. The main component in mouse plasma was amenamevir, accounting for 87.9% of amenamevir-derived components. Our results suggest that the main elimination pathway in mice is oxidative metabolism at a methyl group and a 1,2,3-trisubstituted benzene ring followed by biliary and fecal excretion. Following oral administration of 14 C-amenamevir to mice, 100.63% of the dose (10.06% in urine and 90.46% in feces) was excreted by 96 h post-dose. The underlying mechanism of the improved pharmacokinetic profile of amenamevir was linked to an improved absorption ratio (not hepatic availability) compared to acyclovir, and qualitative differences in elimination (slow metabolism of amenamevir vs rapid urinary excretion of acyclovir/valaciclovir).

Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss.

PubMed

Preuss, H G; Bagchi, D; Bagchi, M; Rao, C V S; Dey, D K; Satyanarayana, S

2004-05-01

The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.

Dietary Sodium Restriction and Association with Urinary Marinobufagenin, Blood Pressure, and Aortic Stiffness

PubMed Central

Fedorova, Olga V.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; Fleenor, Bradley S.; Lakatta, Edward G.; Bagrov, Alexei Y.; Seals, Douglas R.

2013-01-01

Summary Background and objectives Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading. Design, setting, participants, & measurements The hypothesis was that dietary sodium restriction performed in middle-aged/older adults (eight men and three women; 60±2 years) with moderately elevated systolic BP (139±2/83±2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium (77±9 mmol/d) and 5 weeks of a normal-sodium (144±7 mmol/d) diet. Results Urinary marinobufagenin excretion (weekly measurements; 25.4±1.8 versus 30.7±2.1 pmol/kg per day), systolic BP (127±3 versus 138±5 mmHg), and aortic pulse-wave velocity (700±40 versus 843±36 cm/s) were lower during the low- versus normal-sodium condition (all P<0.05). Across all weeks, marinobufagenin excretion was related with systolic BP (slope=0.61, P<0.001) and sodium excretion (slope=0.46, P<0.001). These associations persisted during the normal- but not the low-sodium condition (both P<0.005). Marinobufagenin excretion also was associated with aortic pulse-wave velocity (slope=0.70, P=0.02) and endothelial cell expression of NAD(P)H oxidase-p47phox (slope=0.64, P=0.006). Conclusions These results show, for the first time in humans, that dietary sodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-sodium diets. PMID:23929930

Renal excretion of prostaglandin metabolites, arginine vasopressin, and sodium during endotoxin and endogenous pyrogen induced fever in the goat.

PubMed

Jónasson, H; Basu, S; Andersson, B; Kindahl, H

1984-04-01

Responses to intravenous injections of an endotoxin (E. coli-lipopolysaccharide, 1 microgram/kg b.wt.) and endogenous pyrogen were studied in euhydrated and hyperhydrated goats. The biphasic febrile response to the endotoxin was associated with a pronounced increase in the renal excretion of measured prostaglandin (PG) metabolites (11-ketotetranor PGF metabolites). This increase was time-correlated with the elevation of the rectal temperature, and (in hyperhydrated animals) with an inhibition of the water diuresis and an increase in renal excretion of arginine vasopressin (AVP). Other effects of the endotoxin were an immediate depression of renal Na and K excretion followed by the development of pronounced natriuresis, and a reduction of plasma Fe and Zn concentrations. The appearance of the febrile reactions (peripheral vasoconstriction and shivering) was accompanied by miosis. The maximum elevation of the rectal temperature was significantly greater during euhydration than during hyperhydration. Also endogenous pyrogen elicited miosis concomitant with febrile reactions, and an elevation of the renal excretion of PG metabolites which was closely correlated in time with the monophasic febrile response, and (during hyperhydration) with temporary inhibition of the water diuresis and an increase in the renal AVP excretion. However, the responses were much weaker than the corresponding endotoxin effects. No appreciable changes in renal excretion of Na and K were observed in response to the endogenous pyrogen. It is concluded that the observed effects on renal cation excretion were manifestations of direct endotoxin influences on kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)

Mathematical Model of Ammonia Handling in the Rat Renal Medulla

PubMed Central

Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

2015-01-01

The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID:26280830

[Assessment of dietary intake and urinary excretion of sodium and potassium in adults].

PubMed

Cornejo, Karen; Pizarro, Fernando; Atalah, Eduardo; Galgani, José E

2014-06-01

Hypertension is associated with elevated sodium and low potassium intakes. The determination of sodium and potassium intake by dietary records is inaccurate, being its measurement from 24-h urine collection the reference method. To determine urinary sodium and potassium excretion in adults. To compare dietary sodium and potassium intake and their excretion from an isolated urine sample against the reference method. Seventy healthy adults aged 35 ± 8 years with a body mass index 25 ± 2 kg/m² (36 women) were studied. Urine was collected over 24 h, including an isolated urine sample taken in fasting conditions. Additionally, three 24-h dietary records were performed. Reported sodium and potassium intake was 2,720 ± 567 and 1,068 ± 433 mg/day, respectively. In turn, urinary excretion of sodium and potassium was 4,770 ± 1,532 and 1,852 ± 559 mg/day, respectively. These latter values were significantly higher than those obtained by dietary records. Furthermore, the urinary sodium and potassium excretion estimated from an isolated urine sample was 4,839 ± 1,355 and 1,845 ± 494 mg/day, respectively. These values were similar to those obtained with a 24 h urine collection. Dietary records underestimated electrolyte intake when compared with the reference method. Using an isolated urine sample to estimate electrolyte intake may be a reliable alternative.

Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats.

PubMed

Kubota, Masatoshi; Watanabe, Reiko; Yamaguchi, Miki; Hosojima, Michihiro; Saito, Akihiko; Fujii, Mikio; Fujimura, Shinobu; Kadowaki, Motoni

2016-10-01

We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period. Hepatic lipids and metabolites were measured and renal glomeruli were observed morphologically. HbA1c levels were significantly lower in rats fed REP, compared with C (P<0·05). Compared with C in the liver, REP prevented lipid accumulation (total lipid, TAG and total cholesterol, P<0·01). Liver metabolome analysis indicated that levels of metabolites associated with glycolysis, the pentose phosphate pathway and carnitine metabolism were significantly greater in the REP group than in the C group (P<0·05), suggesting activation of both glucose catabolism and fatty acid oxidation. The metabolite increases promoted by REP may contribute to suppression of liver lipid accumulation. Urinary excretion of albumin and N-acetyl-β-d-glucosaminidase was significantly reduced in rats fed REP for 8 weeks (P<0·01). In addition, there was a distinct suppression of mesangial matrix expansion and glomerular hypertrophy in response to REP (P<0·01). Thus, REP had preventive effects on obese diabetes, fatty liver and diabetic nephropathy.

Exposure of Preschool-Age Greek Children (RHEA Cohort) to Bisphenol A, Parabens, Phthalates, and Organophosphates.

PubMed

Myridakis, Antonis; Chalkiadaki, Georgia; Fotou, Marianna; Kogevinas, Manolis; Chatzi, Leda; Stephanou, Euripides G

2016-01-19

Phthalate esters (PEs), bisphenol A (BPA), and parabens (PBs), which are used in numerous consumer products, are known for their endocrine disrupting properties. Organophosphate chemicals (OPs), which form the basis of the majority of pesticides, are known for their neurotoxic activity in humans. All of these chemicals are associated with health problems to which children are more susceptible. Once they enter the human body, PEs, BPA, PBs, and OPs are metabolized and/or conjugated and finally excreted via urine. Hence, human exposure to these substances is examined through a determination of the urinary concentrations of their metabolites. This study assessed the exposure of Greek preschool-age children to PEs, BPA, PBs, and OPs by investigating the urinary levels of seven PEs metabolites, six PBs, BPA, and six dialkyl phosphate metabolites in five-hundred samples collected from 4-year-old children, subjects of the "RHEA" mother-child cohort in Crete, Greece. Daily intake of endocrine disruptors, calculated for 4 year old children, was lower than the corresponding daily intake for 2.5 year old children, which were determined in an earlier study of the same cohort. In some cases the daily intake levels exceeded the U.S. Environmental Protection Agency Tolerable Daily Intake (TDI) values and the EFSA Reference Doses (RfD) (e.g., for di-2-ethyl-hexyl phthalate, 3.6% and 1% of the children exceeded RfD and TDi, respectively). Exposure was linked to three main sources: PEs-BPA to plastic, PBs-diethyl phthalate to personal hygiene products, and OPs to food.

The arginine-creatine pathway is disturbed in children and adolescents with renal transplants.

PubMed

Andrade, Fernando; Rodríguez-Soriano, Juan; Prieto, José Angel; Elorz, Javier; Aguirre, Mireia; Ariceta, Gema; Martin, Sergio; Sanjurjo, Pablo; Aldámiz-Echevarría, Luis

2008-08-01

Cardiovascular disease is an important cause of morbidity in recipients of renal transplants. The aim of the present study was to analyze the status of the arginine-creatine pathway in such patients, given the relationship between the arginine metabolism and both renal function and the methionine-homocysteine cycle. Twenty-nine children and adolescents (median age 13, range 6-18 years), who had received a renal allograft 14.5-82.0 months before, were recruited for the study. On immunosuppressive therapy, all patients evidenced an adequate level of renal function. Plasma concentrations of homocysteine and glycine were significantly higher, whereas urinary excretions of guanidinoacetate and creatine were significantly lower than controls. Urinary excretions of guanidinoacetate and creatine correlated positively with creatinine clearance. Urinary excretion of creatine was negatively correlated with plasma concentration of homocysteine. The demonstration of disturbances in the arginine-creatine pathway in patients with well-functioning renal transplants and in absence of chronic renal failure represents a novel finding. We speculate that the low urinary excretion of guanidinoacetate and creatine is probably related to the nephrotoxic effect of immunosuppressive therapy and to defective methylation associated with the presence of hyperhomocysteinemia.

[Effects of excess pyridoxine-HCl on growth and urinary excretion of water-soluble vitamins in weaning rats].

PubMed

Fukuwatari, Tsutomu; Itoh, Keiko; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake level of pyridoxine-HCl in humans, we investigated the effects of excess pyridoxine-HCl administration on body weight gain, food intake, tissue weight, and urinary excretion of water-soluble vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0007% pyridoxine-HCl (control diet) or the same diet with 0.1%, 0.5%, 0.8% or 1.0% pyridoxine-HCl for 30 days. The body weight gain in the 0.8% and 1.0% groups, and the total food intake in the 1.0% group were significantly lower than those in the control group. The urinary excretion of pantothenic acid in the pyridoxine-HCl added groups were higher than that in the control group, while excessive pyridoxine-HCl intake did not affect the urinary excretion of other water-soluble vitamins. These results showed that the no-observed-adverse-effect-level (NOAEL) for pyridoxine-HCl was 0.1% in diet, corresponding to 90 mg/kg body weight/day, and lowest-observed-adverse-effect-level (LOAEL) was 0.5% in diet, corresponding to 450 mg/kg body weight/day.

Comparison of plutonium systemic distribution in rats and dogs with published data in humans.

PubMed

Melo, Dunstana R; Weber, Waylon; Doyle-Eisele, Melanie; Guilmette, Raymond A

2014-11-01

This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate injected intravenously in rats and dogs with a comparison of available humans' data. The experimental design for these two studies consisted of eight groups sacrificed at predetermined time-points post exposure. All organs and tissues as well as daily urinary and fecal excretion were analyzed. Liver and skeleton were the organs with the highest (239)Pu uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV administration. By the end of the study (28 days, d), the activity in skeleton and liver was 85% in dogs and 65% in rats. The urinary excretion function seems to be similar for rats, dogs and humans but the daily fecal to urinary excretion ratio differs between species. A rapid clearance from the liver of rats was observed compared to dogs. Skeleton-to-liver ratios are variable between species. Urinary and fecal excretion patterns for dogs are consistent with human data, indicating that dogs seem to represent better the (239)Pu behavior in humans. The data confirm that the better animal model to evaluate the efficacy of (239)Pu chelating compounds is the canine model.

Lack of regulation of 11β-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism

PubMed Central

Sigurjonsdottir, Helga A; Andrew, Ruth; Stimson, Roland H; Johannsson, Gudmundur; Walker, Brian R

2009-01-01

Objective Evidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11β-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer. Design Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism. Methods Twelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-2H4-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11β-HSD1 by appearance of plasma cortisol after oral cortisone, and 11β-HSD1 mRNA levels in subcutaneous adipose biopsies. Results GH withdrawal and reintroduction had no effect on 9,12,12-[2H]3-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11β-HSD1 mRNA. GH withdrawal increased plasma cortisol 30–180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5α-reduced cortisol metabolites. Conclusions In this setting, GH did not regulate 11β-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11β-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11β-HSD1 activity, although dose adjustment may be required in the longer term. PMID:19549748

Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascular disease.

PubMed

Khan, N; Monagas, M; Andres-Lacueva, C; Casas, R; Urpí-Sardà, M; Lamuela-Raventós, R M; Estruch, R

2012-12-01

Epidemiological studies suggest that regular consumption of cocoa-containing products may confer cardiovascular protection, reducing the risk of coronary heart disease (CHD). However, studies on the effects of cocoa on different cardiovascular risk factors are still scarce. The aim of this study was too evaluate the effects of chronic cocoa consumption on lipid profile, oxidized low-density lipoprotein (oxLDL) particles and plasma antioxidant vitamin concentrations in high-risk patients. Forty-two high-risk volunteers (19 men and 23 women, mean age 69.7 ± 11.5 years) were included in a randomized, crossover feeding trial. All received 40g of cocoa powder with 500 mL of skimmed milk/day(C + M) or only 500 mL/day of skimmed milk (M) for 4 weeks in a random order. Before and after each intervention period, plasma lipids, oxLDL and antioxidant vitamin concentrations were measured, as well as urinary cocoa polyphenols metabolites derived from phase II and microbial metabolisms. Compared to M, C + M intervention increases HDLc [2.67 mg/dL (95% confidence intervals, CI, 0.58-4.73; P = 0.008)] and decreases oxLDL levels [-12.3 U/L (CI,-19.3 to -5.2;P = 0.001)]. No changes between intervention groups were observed in vitamins B1, B6, B12, C and E, or folic acid concentrations. In addition, subjects who showed higher increments in urinary cocoa polyphenol metabolites exhibited significant increases in HDLc and significant decreases in oxLDL levels (P < 0.05; all). Consumption of cocoa power with milk modulates the lipid profile in high-risk subjects for CHD. In addition, the relationship observed between the urinary excretion of cocoa polyphenol metabolites and plasma HDLc and oxLDL levels suggests a beneficial role for cocoa polyphenols in lipid metabolism. Copyright © 2011 Elsevier B.V. All rights reserved.

The fractional urinary fluoride excretion of adults consuming naturally and artificially fluoridated water and the influence of water hardness: a randomized trial.

PubMed

Villa, A; Cabezas, L; Anabalón, M; Rugg-Gunn, A

2009-09-01

To assess whether there was any significant difference in the average fractional urinary fluoride excretion (FUFE) values among adults consuming (NaF) fluoridated Ca-free water (reference water), naturally fluoridated hard water and an artificially (H2SiF6) fluoridated soft water. Sixty adult females (N=20 for each treatment) participated in this randomized, double-blind trial. The experimental design of this study provided an indirect estimation of the fluoride absorption in different types of water through the assessment of the fractional urinary fluoride excretion of volunteers. Average daily FUFE values (daily amount of fluoride excreted in urine/daily total fluoride intake) were not significantly different between the three treatments (Kruskal-Wallis; p = 0.62). The average 24-hour FUFE value (n=60) was 0.69; 95% C.I. 0.65-0.73. The results of this study suggest that the absorption of fluoride is not affected by water hardness.

Prediction of urinary nitrogen and urinary urea nitrogen excretion by lactating dairy cattle in northwestern Europe and North America: a meta-analysis.

PubMed

Spek, J W; Dijkstra, J; van Duinkerken, G; Hendriks, W H; Bannink, A

2013-07-01

A meta-analysis was conducted on the effect of dietary and animal factors on the excretion of total urinary nitrogen (UN) and urinary urea nitrogen (UUN) in lactating dairy cattle in North America (NA) and northwestern Europe (EU). Mean treatment data were used from 47 trials carried out in NA and EU. Mixed model analysis was used with experiment included as a random effect and all other factors, consisting of dietary and animal characteristics, included as fixed effects. Fixed factors were nested within continent (EU or NA). A distinction was made between urinary excretions based on either urine spot samples or calculated assuming a zero N balance, and excretions that were determined by total collection of urine only. Moreover, with the subset of data based on total collection of urine, a new data set was created by calculating urinary N excretion assuming a zero N balance. Comparison with the original subset of data allowed for examining the effect of such an assumption on the relationship established between milk urea N (MUN) concentration and UN. Of all single dietary and animal factors evaluated to predict N excretion in urine, MUN and dietary crude protein (CP) concentration were by far the best predictors. Urinary N excretion was best predicted by the combination of MUN, CP, and dry matter intake, whereas UUN was best predicted by the combination of MUN and CP. All other factors did not improve or only marginally improved the prediction of UN or UUN. The relationship between UN and MUN differed between NA and EU, with higher estimated regression coefficients for MUN for the NA data set. Precision of UN and UUN prediction improved substantially when only UN or UUN data based on total collection of urine were used. The relationship between UN and MUN for the NA data set, but not for the EU data set, was substantially altered when UN was calculated assuming a zero N balance instead of being based on the total collection of urine. According to results of the present meta-analysis, UN and UUN are best predicted by the combination of MUN and CP and that, in regard to precision and accuracy, prediction equations for UN and UUN should be derived from the total collection of urine. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Diet effects on urine composition of cattle and N2O emissions.

PubMed

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 urine deposition or manure application strongly influence N2O release. Major dietary strategies to mitigating N2O emission from cattle operations include reducing dietary N content or increasing energy content, and increasing dietary mineral content to increase urine volume. For further reduction of N2O emission, an integrated animal nutrition and excreta management approach is required.

Urinary Sodium and Potassium Excretion and Carotid Atherosclerosis in Chinese Men and Women

PubMed Central

Dai, Xiao-Wei; Wang, Cheng; Xu, Ying; Guan, Ke; Su, Yi-Xiang; Chen, Yu-Ming

2016-01-01

Limited studies have examined the association between sodium (Na) and potassium (K) levels and the risk of atherosclerosis. This study examined whether higher Na and Na/K levels and low K levels were independent risk factors for atherosclerosis. This community-based cross-sectional study included 3290 subjects (1067 men and 2223 women) 40 to 75 years of age in Guangzhou, China, between 2011 and 2013. Urinary excretion of Na and K were measured from the first morning void, and creatinine-adjusted values were used. The intima-media thickness (IMT) of the carotid common artery and the carotid bifurcation was measured with high-resolution B-mode ultrasonography. Dietary K and Na intake and other covariates were obtained by face-to-face interviews. A significant positive association was seen between urinary Na excretion and carotid atherosclerosis after adjustment for age, sex, and other lifestyle covariates. The odds ratios (OR) and 95% confidence interval (CI) of the highest (vs. lowest) quartile of urinary Na were 1.32 (1.04–1.66) for carotid plaques, 1.48 (1.18–1.87) for increased common carotid artery IMT, and 1.55 (1.23–1.96) for increased carotid bifurcation IMT (all p-trend < 0.01). A similar positive association was observed between urinary Na/K levels and carotid plaque and increased IMT, and between dietary Na intake and increased bifurcation IMT. Regarding potassium data, we only found a significantly lower presence of carotid plaque (OR 0.72, 95% CI 0.57–0.91) for quartile 2 (vs. 1) of urinary K. Our findings suggest that higher levels of urinary excretion Na and Na/K are significantly associated with greater presence of carotid atherosclerosis in Chinese adults. PMID:27706075

Association of urinary citrate excretion, pH, and net gastrointestinal alkali absorption with diet, diuretic use, and blood glucose concentration.

PubMed

Perinpam, Majuran; Ware, Erin B; Smith, Jennifer A; Turner, Stephen T; Kardia, Sharon L R; Lieske, John C

2017-10-01

Urinary citrate (Ucit) protects against urinary stone formation. Acid base status and diet influence Ucit. However, the effect of demographics, diet, and glucose metabolism on Ucit excretion, urinary pH (U-pH) and net gastrointestinal alkali absorption (NAA) are not known. Twenty-four hour urine samples, blood glucose, creatinine, and cystatin C were obtained from non-Hispanic white sibships in Rochester, MN ( n  = 446; 64.5 ± 9 years; 58% female). Diet was assessed by a food frequency questionnaire. The impact of blood glucose, demographics and dietary elements on Ucit excretion, U-pH, and NAA were evaluated in bivariate and multivariable models and interaction models that included age, sex, and weight. NAA significantly associated with Ucit and U-pH In multivariate models Ucit increased with age, weight, eGFR C ys , and blood glucose, but decreased with loop diuretic and thiazide use. U-pH decreased with serum creatinine, blood glucose, and dietary protein but increased with dietary potassium. NAA was higher in males and increased with age, weight, eGFR C ys and dietary potassium. Significant interactions were observed for Ucit excretion with age and blood glucose, weight and eGFR C ys, and sex and thiazide use. Blood glucose had a significant and independent effect on U-pH and also Ucit. This study provides the first evidence that blood glucose could influence urinary stone risk independent of urinary pH, potentially providing new insight into the association of obesity and urinary stone disease. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy.

PubMed

Puar, Troy; Engels, Manon; van Herwaarden, Antonius E; Sweep, Fred C G J; Hulsbergen-van de Kaa, Christina; Kamphuis-van Ulzen, Karin; Chortis, Vasileios; Arlt, Wiebke; Stikkelbroeck, Nike; Claahsen-van der Grinten, Hedi L; Hermus, Ad R M M

2017-02-01

Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare. We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement. Hormonal tests confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing disease. Surgical resection of the testicular tumors led to clinical and biochemical remission. Gene expression analysis of the tumor tissue by quantitative polymerase chain reaction showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 × 105 (CYP11B1), 1.8 × 102 (CYP11B2), and 6.3 × 104 (MC2R) times higher than nonsteroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2 fivefold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol, and total glucocorticoids. Leydig-specific genes were 4.3 × 101 (LHCGR) and 9.3 × 100 (HSD17B3) times higher than control, and urinary steroid profiling showed twofold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone but unresponsive to human chorionic gonadotropin stimulation, supporting the role of ACTH, but not luteinizing hormone, in regulating tumor-specific steroid excess. We report bilateral testicular tumors occurring in a patient with recurrent Cushing disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia, suggesting the presence of pluripotent cells even in patients without congenital adrenal hyperplasia. Copyright © 2017 by the Endocrine Society

The rate of aucubin, a secondary metabolite in Plantago lanceolata and potential nitrification inhibitor, needed to reduce ruminant urine patch nitrous oxide emissions

NASA Astrophysics Data System (ADS)

Gardiner, C. A.; Clough, T.; Cameron, K.; Di, H.; Edwards, G. R.

2017-12-01

Nitrous oxide (N2O) losses derived from grazing ruminant livestock urine patches account for 40% of global N2O emissions. It has been shown that Plantago lanceolata, an herb species used in grazed pastures, contains an active secondary metabolite (aucubin) that has the potential to be excreted by grazing ruminants and inhibit nitrification in the urine patch, a key step in soil N2O production. However, the urinary excretion rate of aucubin needed to significantly reduce urine patch N2O emissions remains unknown. Aucubin was dissolved in bovine urine at three rates (47, 243, and 486 kg ha-1), based on rates used in Dietz et al. (2013) and the calculated highest potential aucubin application rate, from Gardiner et al. (2017). A control, along with a urine treatment and the three aucubin treatments (all urine applied at 700 kg N ha-1), was applied to 20 g soil and incubated in the laboratory for 35 d. Soils were monitored for surface pH, inorganic N concentration (NH4+/NO3-), and gas (N2O and CO2) fluxes. This experiment is currently underway and the results will be presented at the conference. Dietz M, Machill S, Hoffmann H, Schmidtke K 2013. Inhibitory effects of Plantago lanceolata L. on soil N mineralization. Plant and Soil 368: 445-458. Gardiner CA, Clough TJ, Cameron KC, Di HJ, Edwards GR, de Klein CAM 2017. The potential inhibitory effects of Plantago lanceolata and its active secondary metabolite aucubin on soil nitrification and nitrous oxide emissions under ruminant urine patch conditions. Manuscript submitted for publication.

Drug-drug interaction and doping: Effect of non-prohibited drugs on the urinary excretion profile of methandienone.

PubMed

Mazzarino, Monica; Khevenhüller-Metsch, Franziska L; Fiacco, Ilaria; Parr, Maria Kristina; de la Torre, Xavier; Botrè, Francesco

2018-05-15

The potential consequences of drug-drug interactions on the excretion profile of the anabolic androgenic steroid methandienone (17β-hydroxy-17α-methylandrosta-1,4-dien-3-one) are discussed here. More specifically, we have evaluated by in vitro and in vivo experiments the effects of seven non-prohibited drugs (fluconazole, ketoconazole, itraconazole, miconazole, fluoxetine, paroxetine and nefazodone) on the main metabolic pathways of methandienone. These are selected among those most commonly used by the athletes. The in vitro assays were based on the use of human liver microsomes, specific recombinant enzyme isoforms of cytochrome P450 and uridine 5'-diphospho-glucuronosyl-transferase. The in vivo study was performed by analyzing urines collected after the oral administration of methandienone with and without the co-administration of ketoconazole. Methandienone and its metabolites were determined by liquid chromatography-mass spectrometry-based techniques after sample pre-treatment including an enzymatic hydrolysis step (performed only for the investigation on phase II metabolism) and liquid/liquid extraction with t-butyl methyl-ether. The results from the in vitro experiments showed that the formation of the hydroxylated and dehydrogenated metabolites was significantly reduced in the presence of itraconazole, ketoconazole, miconazole and nefazodone, whereas the production of the 18-nor-hydroxylated metabolites and glucuronidation reactions was reduced significantly only in the presence of ketoconazole and miconazole. The analysis of the post-administration samples confirmed the in vitro observations, validating the hypothesis that drug-drug interaction may cause significant alterations in the metabolic profile of banned drugs, making their detection during doping control tests more challenging. This article is protected by copyright. All rights reserved.

Atypical excretion profile and GC/C/IRMS findings may last for nine months after a single dose of nandrolone decanoate.

PubMed

Palonek, Elzbieta; Ericsson, Magnus; Gårevik, Nina; Rane, Anders; Lehtihet, Mikael; Ekström, Lena

2016-04-01

The use of the anabolic androgenic steroid nandrolone and its prohormones is prohibited in sport. A common route of nandrolone administration is intramuscular injections of a nandrolone ester. Here we have investigated the detection time of nandrolone and 19-norandrosterone and 19-noretiocholanolone metabolites in eleven healthy men after the administration of a 150 mg dose of nandrolone decanoate. The urinary concentrations of nandrolone and the metabolites were monitored by GC-MS/MS for nine months and in some samples the presence of 19-norandrosterone was confirmed by GC/C/IRMS analysis. The participants were genotyped for polymorphisms in PDE7B1 and UGT2B15 genes previously shown to influence the activation and inactivation of nandrolone decanoate. There were large inter-individual variations in the excretion rate of nandrolone and the metabolites, although not related to genetic variations in the UGT2B15 (rs1902023) and PDE7B1 (rs7774640) genes. After the administration, 19-norandrosterone was found at 2-8-fold higher concentrations than 19-noretiocholanolone. We showed that nandrolone doping can be identified 4 and 9 months after the injection of only one single dose in six and three individuals, respectively. We also noted that GC/C/IRMS confirms the presence of exogenous 19-norandrosterone in the urine samples, showing δ13 values around -32 ‰. This was true even in a sample that was not identified as an atypical finding after the GC-MS/MS analysis further showing the power of using GC/C/IRMS in routine anti-doping settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Urinary type IV collagen excretion predicts subsequent declining renal function in type 2 diabetic patients with proteinuria.

PubMed

Katavetin, Pisut; Katavetin, Paravee; Susantitaphong, Paweena; Townamchai, Natavudh; Tiranathanagul, Khajohn; Tungsanga, Kriang; Eiam-Ong, Somchai

2010-08-01

Baseline urinary type IV collagen excretion was negatively correlated with the subsequent GFR change (r(s)=-0.39, p=0.04) in our cohort of 30 type 2 diabetic patients with proteinuria. Therefore, it could be used to predict subsequent declining renal function in type 2 diabetic patients with proteinuria. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Dramatic elevation in urinary amino terminal titin fragment excretion quantified by immunoassay in Duchenne muscular dystrophy patients and in dystrophin deficient rodents.

PubMed

Robertson, Alan S; Majchrzak, Mark J; Smith, Courtney M; Gagnon, Robert C; Devidze, Nino; Banks, Glen B; Little, Sean C; Nabbie, Fizal; Bounous, Denise I; DiPiero, Janet; Jacobsen, Leslie K; Bristow, Linda J; Ahlijanian, Michael K; Stimpson, Stephen A

2017-07-01

Enzyme-linked and electrochemiluminescence immunoassays were developed for quantification of amino (N-) terminal fragments of the skeletal muscle protein titin (N-ter titin) and qualified for use in detection of urinary N-ter titin excretion. Urine from normal subjects contained a small but measurable level of N-ter titin (1.0 ± 0.4 ng/ml). A 365-fold increase (365.4 ± 65.0, P = 0.0001) in urinary N-ter titin excretion was seen in Duchene muscular dystrophy (DMD) patients. Urinary N-ter titin was also evaluated in dystrophin deficient rodent models. Mdx mice exhibited low urinary N-ter titin levels at 2 weeks of age followed by a robust and sustained elevation starting at 3 weeks of age, coincident with the development of systemic skeletal muscle damage in this model; fold elevation could not be determined because urinary N-ter titin was not detected in age-matched wild type mice. Levels of serum creatine kinase and serum skeletal muscle troponin I (TnI) were also low at 2 weeks, elevated at later time points and were significantly correlated with urinary N-ter titin excretion in mdx mice. Corticosteroid treatment of mdx mice resulted in improved exercise performance and lowering of both urinary N-ter titin and serum skeletal muscle TnI concentrations. Low urinary N-ter titin levels were detected in wild type rats (3.0 ± 0.6 ng/ml), while Dmd mdx rats exhibited a 556-fold increase (1652.5 ± 405.7 ng/ml, P = 0.002) (both at 5 months of age). These results suggest that urinary N-ter titin is present at low basal concentrations in normal urine and increases dramatically coincident with muscle damage produced by dystrophin deficiency. Urinary N-ter titin has potential as a facile, non-invasive and translational biomarker for DMD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

[Absence of effect of propranolol on urinary excretion of 3-methylhistidine in hyperthyroidism].

PubMed

Beylot, M; Riou, J P; Sautot, G; Mornex, R

Lean body mass and muscle protein breakdown were evaluated in euthyroid and hyperthyroid subjects by measuring the urinary excretion of creatinine and 3-methylhistidine. Since catecholamines probably have an inhibitory effect on muscle protein catabolism through a beta-receptor mechanism, the effects of propranolol on 3-methylhistidine excretion were also evaluated in hyperthyroid subjects. Hyperthyroid subjects had a lower lean body mass (34.9 +/- 6.3 kg versus 47.7 +/- 8.9 kg, p less than 0.001) and a greater 3-methylhistidine excretion (25.1 +/- 7.4 versus 19.0 +/- 4.8 mumol/mmol creatinine, p less than 0.05) than euthyroid subjects. Propranolol administered orally to hyperthyroid subjects decreased pulse rate (p less than 0.01) and plasma triiodothyronine concentrations (from 5.40 +/- 2.28 to 3.61 +/- 1.61 nmol/l, p less than 0.01), but did not modify urinary 3-methylhistidine excretion (24.8 +/- 8.7 versus 25.1 +/- 7.4 mumol/mmol creatinine). These results suggest that muscle wasting in hyperthyroidism is related to increased protein catabolism. This increased protein breakdown is not modified by short term administration of propranolol, a beta-blocking agent widely used in the management of hyperthyroidism.

Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations

PubMed Central

Chardon, Laurence; El Hajji Ridah, Ines; Brossaud, Julie

2017-01-01

Context Biogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours. Objective To re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays. Methods Bibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences. Results 5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.). Conclusion Revisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays. PMID:28566493

Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations.

PubMed

Corcuff, Jean-Benoît; Chardon, Laurence; El Hajji Ridah, Ines; Brossaud, Julie

2017-08-01

Biogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours. To re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays. Bibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences. 5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.). Revisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays. © 2017 The authors.

[Effect of a modified low protein and low fat diet on histologic changes and metabolism in kidneys in an experimental model of polycystic kidney disease].

PubMed

Banković-Calić, Neda; Ogbori, Malkom R; Nicman, Evin

2002-01-01

Dietary protein restriction slows progression in numerous animal models of renal diseases. Flax seed has also demonstrated useful anti-inflammatory properties in a number of animal models and human diseases. We undertook several studies to determine if feeding with low protein casein, soy diet and flax seed diet would ameliorate renal injury in Han:SPRD-cy rat model of polycystic kidney disease. Male offspring of Han:SPRD-cy heterozygotes received protein modified diet: ad libidum LP 8% casein in test or 20% casein in control group for 8 weeks; 20% heat treated soy protein or 20% casein in control group two separate studies for 8 weeks ad libidum and pair feeding in 6 weeks; and 10% flax seed diet or control rat chow for 8 weeks from weaning. Tissue was harvested for histological assessment and metabolic changes in lipids, citric acid metabolites and osmolytes. Morphometrically after histochemical and immunohistochemical staining cystic changes, renal tubular proliferation and apoptosis, number of interstitial cells/macrophages infiltration and interstitial fibrosis were measured. Gas chromatography was used for lipid analysis in renal and liver tissue. 1-HNMR spectroscopy was used for urine and tissue organic anion and osmolytes content analysis. RESULTS IN PROTEIN MODIFIED DIET: Casein low protein as well as soy protein fed animals demonstrated reduced PKD pathology: significant reduction in cystic changes, interstitial inflammation and fibrosis and also reduction in tubular cells proliferation and apoptosis. Pair feeding protocol in second soy diet study confirmed that significant effect on renal histology was not because of protein deprivation and growth retardation. 1-H NMR spectroscopy revealed that progression of chronic renal failure in Han:SPRD-cy rat PKD is associated with renal depletion of citric acid cycle metabolite and betaine. Amelioration of PKD by soy protein diet is associated with renal retention of citric acid cycle anions, despite increased excretion and preservation of betaine in renal tissue. Soy feeding increased both hepatic and renal content of linoleic acid and increased renal alpha linolenic acid content, while decreased arachidonic hepatic content. RESULTS IN FLAX SEED SUPPLEMENTATION IN DIET: Flax seed fed animals had moderate decrease in cystic size and less interstitial inflammation and fibrosis while there were no differences in epithelial cell apoptosis and proliferation. Lipid analysis revealed significant renal enrichment of 18 and 20 carbon omega 3 polyunsaturated fatty acids. In flax fed animals there was an increased urinary citrate excretion without significant changes in urinary ammonia excretion, so increased citrate excretion was not due to alkaline effect of the diet. Kidney tissue 1H NMR spectroscopy revealed that disease amelioration was associated with tissue retention of succinate and betaine. Effect on histology: Low casein and soy feeding ameliorates Han: SPRD-cy rat polycystic kidney disease reducing both tubular remodeling and interstitial inflammation and fibrosis, while flax seed diet effect appears to be through moderation of associated interstitial nephritis. Metabolic effect: Soy diet alters the renal content of polyunsaturated fatty acids and enriched renal betaine content with retention of citric acid cycle metabolites despite increased excretion. Flax seed diet alters renal content of polyunsaturated fatty acids and promotes the formation of less inflammatory classes of renal prostanoides. Flax seed diet also enriched renal content of betaine and succinate. Amelioration of Hans:SPRD-cy rat polycystic kidney disease by diet is associated with alteration in the handling of citric acid cycle metabolites and betaine, and also in content of polyunsaturated fatty acids in kidneys and liver. Metabolic pathways in dietary modified renal pathology have to be established.

Vitamin C activity of dehydroascorbic acid in humans--association between changes in the blood vitamin C concentration or urinary excretion after oral loading.

PubMed

Tsujimura, Masaru; Higasa, Shizu; Nakayama, Kazuhiro; Yanagisawa, Yoshiko; Iwamoto, Sadahiko; Kagawa, Yasuo

2008-08-01

We performed oral loading of AsA or DAsA (1 mmol) in subjects who had consumed a diet low in vitamin C (C) (C< or =5 mg/d) for 3 d before loading, and measured urinary and blood vitamin C. Since the crossover method was used, the same experiment was repeated after an interval of about 1 mo in each subject. The results of the experiment including a total of 17 subjects for 2005 and 2006, were as follows. (1) There were marked individual differences in urinary C excretion. (2) The C level in 24-h urine after C loading did not differ between the two orally administered C forms (AsA and DAsA). (3) C excretion between 0 and 3 h after C loading was significantly higher (p<0.05) for the DAsA group, while those between 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after C loading were significantly higher (p<0.05 or p<0.01) for the AsA group. (4) The blood C concentration and the increase in C 1 h after C loading were significantly higher (p<0.05 and p<0.01, respectively) in the DAsA than in the AsA group. (5) Evaluation of the association between C metabolism and the single nucleotide polymorphisms of glutathione S-transferase P (GSTP) 1-1 showed a lower urinary C excretion and a significantly lower C level in 24-h urine (p<0.05) after AsA loading, and a significantly lower urinary C excretion between 0 and 3 h after DAsA loading (p<0.05) for the GA heterozygotes than for the AA homozygotes. Considering the activity of C as DAsA in humans, based on urinary and blood C levels after a single loading of C, the utilization of DAsA is equivalent to that of AsA, although the metabolic turnover time is different. The involvement of polymorphisms in the xenobiotic metabolizing enzyme, GSTP1-1, in C metabolism, particularly urinary C excretion, was also clarified. This demonstrates the necessity of considering gene polymorphisms in determining individual C requirements. An abstract of this paper was reported by the Vitamin C Research Committee (Ochanomizu University) in 2007.

Factors Associated With High Sodium Intake Based on Estimated 24-Hour Urinary Sodium Excretion: The 2009-2011 Korea National Health and Nutrition Examination Survey.

PubMed

Hong, Jae Won; Noh, Jung Hyun; Kim, Dong-Jun

2016-03-01

Although reducing dietary salt consumption is the most cost-effective strategy for preventing progression of cardiovascular and renal disease, policy-based approaches to monitor sodium intake accurately and the understanding factors associated with excessive sodium intake for the improvement of public health are lacking. We investigated factors associated with high sodium intake based on the estimated 24-hour urinary sodium excretion, using data from the 2009 to 2011 Korea National Health and Nutrition Examination Survey (KNHANES). Among 21,199 adults (≥19 years of age) who participated in the 2009 to 2011 KNHANES, 18,000 participants (weighted n = 33,969,783) who completed urinary sodium and creatinine evaluations were analyzed in this study. The 24-hour urinary sodium excretion was estimated using Tanaka equation. The mean estimated 24-hour urinary sodium excretion level was 4349 (4286-4413) mg per day. Only 18.5% (weighted n = 6,298,481/3,396,973, unweighted n = 2898/18,000) of the study participants consumed less the 2000 mg sodium per day. Female gender (P < 0.001), older age (P < 0.001), total energy intake ≥50 percentile (P < 0.005), and obesity (P < 0.001) were associated with high sodium intake, even after adjusting for potential confounders. Senior high school/college graduation in education and managers/professionals in occupation were associated with lower sodium intake (P < 0.001). According to hypertension management status, those who had hypertension without medication consumed more sodium than those who were normotensive. However, those who receiving treatment for hypertension consumed less sodium than those who were normotensive (P < 0.001). The number of family members, household income, and alcohol drinking did not affect 24-hour urinary sodium excretion. The logistic regression analysis for the highest estimated 24-hour urinary sodium excretion quartile (>6033 mg/day) using the abovementioned variables as covariates yielded identical results. Our data suggest that age, sex, education level, occupation, total energy intake, obesity, and hypertension management status are associated with excessive sodium intake in Korean adults using nationally representative data. Factors associated with high sodium intake should be considered in policy-based interventions to reduce dietary salt consumption and prevent cardiovascular disease as a public health target.

Early Biochemical Effects of an Organic Mercury Fungicide on Infants: ``Dose Makes the Poison''

NASA Astrophysics Data System (ADS)

Gotelli, Carlos A.; Astolfi, Emilio; Cox, Christopher; Cernichiari, Elsa; Clarkson, Thomas W.

1985-02-01

Phenylmercury absorbed through the skin from contaminated diapers affected urinary excretion in infants in Buenos Aires. The effects were reversible and quantitatively related to the concentration of urinary mercury. Excretion of γ -glutamyl transpeptidase, an enzyme in the brush borders of renal tubular cells, increased in a dose-dependent manner when mercury excretion exceeded a ``threshold'' value. Urine volume also increased but at a higher threshold with respect to mercury. The results support the threshold concept of the systemic toxicity of metals. γ -Glutamyl transpeptidase is a useful and sensitive marker for preclinical effects of toxic metals.

Renal function in sheep during infusion of alkali metal ions into the renal artery.

PubMed Central

Beal, A M; Harrison, F A

1975-01-01

1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron. PMID:236381

Metabolomics Approach to Male Lower Urinary Tract Symptoms: Identification of Possible Biomarkers and Potential Targets for New Treatments.

PubMed

Mitsui, Takahiko; Kira, Satoru; Ihara, Tatsuya; Sawada, Norifumi; Nakagomi, Hiroshi; Miyamoto, Tatsuya; Shimura, Hiroshi; Yokomichi, Hiroshi; Takeda, Masayuki

2018-05-01

We identified metabolites using a metabolomics approach and investigated the association between these metabolites and lower urinary tract symptoms. We used a 24-hour bladder diary and I-PSS (International Prostate Symptom Score) to assess micturition behavior and lower urinary tract symptoms in 58 male patients without apparent neurological disease. Lower urinary tract symptoms were defined as a total I-PSS score of 8 or greater. Patients with a score of 7 or less were placed in the control group. A comprehensive study of plasma metabolites was also performed by capillary electrophoresis time-of-flight mass spectrometry. Metabolites were compared between the lower urinary tract symptoms and control groups using the Mann-Whitney U test. Biomarkers of male lower urinary tract symptoms from the metabolites were analyzed using multivariable logistic regression analysis to determine the OR. Of the 58 men 32 were in the lower urinary tract symptoms group and the remaining 26 were in the control group. The 24-hour bladder diary showed that nocturnal urine volume, 24-hour micturition frequency, nocturnal micturition frequency and the nocturia index were significantly higher in the lower urinary tract symptoms group. Metabolomics analysis identified 60 metabolites from patient plasma. Multivariate analysis revealed that increased glutamate and decreased arginine, asparagine and inosine monophosphate were significantly associated with lower urinary tract symptoms in males. Decreases in citrulline and glutamine could also be associated with male lower urinary tract symptoms. Male lower urinary tract symptoms may develop due to abnormal metabolic processes in some pathways. Potential new treatments for lower urinary tract symptoms can be developed by identifying changes in the amino acid profiles. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Association of urinary sodium/creatinine ratio with bone mineral density in postmenopausal women: KNHANES 2008-2011.

PubMed

Kim, Sung-Woo; Jeon, Jae-Han; Choi, Yeon-Kyung; Lee, Won-Kee; Hwang, In-Ryang; Kim, Jung-Guk; Lee, In-Kyu; Park, Keun-Gyu

2015-08-01

Accumulating evidence shows that high sodium chloride intake increases urinary calcium excretion and may be a risk factor for osteoporosis. However, the effect of oral sodium chloride intake on bone mineral density (BMD) and risk of osteoporosis has been inadequately researched. The aim of the present study was to determine whether urinary sodium excretion (reflecting oral sodium chloride intake) associates with BMD and prevalence of osteoporosis in postmenopausal women. This cross-sectional study involved a nationally representative sample consisting of 2,779 postmenopausal women who participated in the Korea National Health and Nutritional Examination Surveys in 2008-2011. The association of urinary sodium/creatinine ratio with BMD and other osteoporosis risk factors was assessed. In addition, the prevalence of osteoporosis was assessed in four groups with different urinary sodium/creatinine ratios. Participants with osteoporosis had significantly higher urinary sodium/creatinine ratios than the participants without osteoporosis. After adjusting for multiple confounding factors, urinary sodium/creatinine ratio correlated inversely with lumbar spine BMD (P = 0.001). Similarly, when participants were divided into quartile groups according to urinary sodium/creatinine ratio, the average BMD dropped as the urinary sodium/creatinine ratio increased. Multiple logistic regression analysis revealed that compared to quartile 1, quartile 4 had a significantly increased prevalence of lumbar spine osteoporosis (odds ratios 1.346, P for trend = 0.044). High urinary sodium excretion was significantly associated with low BMD and high prevalence of osteoporosis in lumbar spine. These results suggest that high sodium chloride intake decreases lumbar spine BMD and increases the risk of osteoporosis in postmenopausal women.

Clinical Pharmacokinetics of Levornidazole in Elderly Subjects and Dosing Regimen Evaluation Using Pharmacokinetic/Pharmacodynamic Analysis.

PubMed

Guo, Beining; He, Gaoli; Wu, Xiaojie; Yu, Jicheng; Cao, Guoying; Li, Yi; Fan, Yaxin; Chen, Yuancheng; Shi, Yaoguo; Zhang, Yingyuan; Zhang, Jing

2017-07-01

Levornidazole, the levo-isomer of ornidazole, is a third-generation nitroimidazole derivative newly developed after metronidazole, tinidazole, and ornidazole. An open-label, parallel-controlled, single-dose study was conducted for the investigation of the pharmacokinetic (PK) profile of levornidazole and its metabolites in healthy elderly Chinese subjects, and for the evaluation of 2 dosing regimens in the elderly. Levornidazole was intravenously administered at 500 mg to healthy elderly (aged 60-80 years) or young subjects (aged 19-45 years). The PK profiles of levornidazole and its metabolites in elderly subjects were evaluated and compared with those in the young group. WinNonlin software was used for simulating the PK profile of levornidazole in the elderly population following the dosing regimens of 500 mg BID and 750 mg once daily for 7 days. Monte Carlo simulation was used for estimating the cumulative fraction of response and probability of target attainment of both dosing regimens against Bacteroides spp. The C max , AUC 0-24, and AUC 0-∞ values of levornidazole in the elderly group were 11.98 μg/mL, 131.36 μg·h/mL, and 173.61 μg·h/mL, respectively. The t 1/2 , CL t , and mean residence time from time 0 to infinity were 12.21 hours, 2.91 L/h, and 16.46 hours. The metabolic ratios of metabolites (M) 1, 2, 4, and 6 were <3.0%, and that of M16 was 17.70%. The urinary excretion values of levornidazole, M1, M2, M4, M6, and M16 over 96 hours were 10.21%, 0.92%, ~0%, 2.69%, 0.54%, and 41.98%. The PK properties of levornidazole and the urinary excretion of all metabolites were not statistically different between the 2 groups. The cumulative fraction of response was >90% against B fragilis and other Bacteroides spp, and the probability of target attainment was >90% when the minimum inhibitory concentration was ≤1 μg/mL, in both groups. No dosing regimen adjustment is suggested when levornidazole is used in elderly patients with normal hepatic functioning and mild renal dysfunction. The findings from the PK/PD analysis imply that both regimens may achieve satisfactory clinical and microbiological efficacy against anaerobic infections in elderly patients. Chinese Clinical Trial Registry (http://www.chictr.org.cn) identifier: ChiCTR-OPC-16007938. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Urinary oxalate to creatinine ratios in healthy Turkish schoolchildren.

PubMed

Dursun, Ismail; Çelik, İlknur; Poyrazoglu, Hakan M; Köse, Kader; Tanrıkulu, Esen; Sahin, Habibe; Yılmaz, Kenan; Öztürk, Ahmet; Yel, Sibel; Gündüz, Zübeyde; Düşünsel, Ruhan

2017-11-01

we aimed to establish reference values for urinary oxalate to creatinine ratios in healthy children aged 6-15 years and to investigate the relationship between their nutritional habits and oxalate excretion. Random urine specimens from 953 healthy children aged 6-15 years were obtained and analyzed for oxalate and creatinine. Additionally, a 24-h dietary recall form was prepared and given to them. The ingredient composition of the diet was calculated. The children were divided into three groups according to age: Group I (69 years, n = 353), Group II (10-12 years, n = 335), and Group III (13-15 years, n = 265). The 95th percentile of the oxalate to creatinine ratio for subjects aged 6-9, 10-12, and 13-15 years were 0.048, 0.042, and 0.042 mg/mg, respectively. The oxalate to creatinine ratio was significantly higher in Group 1 than in Group 2 and Group 3. Urinary oxalate excretion was positively correlated with increased protein intake and negatively correlated with age. A significant positive correlation was determined between urinary oxalate excretion and the proline, serine, protein, and glycine content of diet. Dietary proline intake showed a positive correlation with the urine oxalate to creatinine ratio and was found to be an independent predictor for urinary oxalate. These data lend support to the idea that every country should have its own normal reference values to determine the underlying metabolic risk factor for kidney stone disease since regional variation in the dietary intake of proteins and other nutrients can affect normal urinary excretion of oxalate.

Dietary isoflavone absorption, excretion, and metabolism in captive cheetahs (Acinonyx jubatus).

PubMed

Whitehouse-Tedd, Katherine M; Cave, Nicholas J; Ugarte, Claudia E; Waldron, Lucy A; Prasain, Jeevan K; Arabshahi, Alireza; Barnes, Stephen; Thomas, David G

2011-12-01

Dietary isoflavones, capable of influencing reproductive parameters in domestic cats (Felis catus), have been detected in commercial diets fed to captive cheetahs (Acinonyx jubatus). However, the absorptive and metabolic capacity of cheetahs towards isoflavones has not yet been studied. Experiments were designed to describe the plasma concentration-time curve, metabolite profile, and urinary and fecal excretion of genistein and daidzein in cheetahs following consumption of isoflavones. Four adult cheetahs were administered a single oral bolus of genistein and daidzein, and five juvenile cheetahs consuming a milk replacer formula found to contain isoflavones were also included. Urine was collected from all animals, and blood and feces were also collected from adult cheetahs following isoflavone exposure. Samples were analyzed for isoflavone metabolite concentration by liquid chromatography-electrospray ionization-multiple reaction ion monitoring mass spectrometry and high-performance liquid chromatography. Sulfate conjugates were the primary metabolites detected of both genistein and daidzein (60-80% of total isoflavones present) in the plasma and urine of cheetahs. A smaller proportion of daidzein was detected as conjugates in the urine of juvenile cheetahs, compared to adult cheetahs. Other metabolites included unconjugated genistein and daidzein, O-desmethylangolensin, and dihydrodaidzein, but not equol. Only 33% of the ingested genistein dose, and 9% of daidzein, was detected in plasma from adult cheetahs. However, of the ingested dose, 67% of genistein and 45% of daidzein were detected in the feces of adults. This study revealed that cheetahs appear efficient in their conjugation of absorbed dietary isoflavones and only a small fraction of ingested dose is absorbed. However, the capacity of the cheetah to conjugate genistein and daidzein with sulfate moieties appears lower than reported in the domestic cat. This may confer greater opportunity for biologic activity of isoflavones in the cheetah than would be predicted from findings in the domestic cat. However, further investigation is required.

The relationship between cognitive function, depressive behaviour and sleep quality with 24-h urinary sodium excretion in patients with essential hypertension.

PubMed

Afsar, Baris

2013-03-01

Various studies have shown that sodium intake is related to increased blood pressure. However, the relationship between sodium intake and cognitive function and depression has not previously been studied. The objective of this study was to investigate the relationship between 24-h sodium excretion with cognitive function, depression and sleep quality in patients newly diagnosed with essential hypertension. All patients underwent history taking, physical examination, blood pressure measurement, 12-lead ECG evaluation, routine urine analysis, biochemical analysis and 24-h urine collection to measure urinary sodium and protein excretion and creatinine clearance, evaluation of cognitive function, depressive behaviour and sleep quality. In total, 119 patients newly diagnosed with essential hypertension (50 men and 69 women aged 54.2 ± 16.1 years) were enrolled. The 24-h urinary sodium excretion of the patients was 204.0 ± 240.4 mEq/day. The Standardized Mini Mental State Examination (SMMSE), Pittsburgh Sleep Quality Index and Beck Depression Inventory scores of the patients were 26.0 ± 2.7, 5.6 ± 3.1 and 21.6 ± 13.5, respectively. Spearman correlation analysis revealed that 24-h urinary sodium excretion was correlated with age (rho -0.258, p = 0.005), systolic blood pressure (rho 0.219, p = 0.017), diastolic blood pressure (rho 0.195, p = 0.034), creatinine clearance (rho 0.414, p < 0.0001) and SMMSE score (rho -0.257, p = 0.005). Stepwise linear regression of independent factors revealed that gender (p < 0.0001), creatinine clearance (p < 0.0001), systolic blood pressure (p = 0.031) and SMMSE score (p < 0.0001) were independently related to logarithmically converted 24-h sodium excretion. The current study demonstrated that better cognitive function, but not depressive behaviour and sleep disturbance, is related to decreased sodium intake as evaluated by 24-h urinary sodium excretion. Studies are needed to highlight the mechanisms regarding the relationship between cognitive function and sodium intake.

Diagnostic Value of Urinary Mevalonic Acid Excretion in Patients with a Clinical Suspicion of Mevalonate Kinase Deficiency (MKD).

PubMed

Jeyaratnam, Jerold; Ter Haar, Nienke M; de Sain-van der Velden, Monique G M; Waterham, Hans R; van Gijn, Mariëlle E; Frenkel, Joost

2016-01-01

In patients suffering from mevalonate kinase deficiency (MKD), the reduced enzyme activity leads to an accumulation of mevalonic acid which is excreted in the urine. This study aims to evaluate the diagnostic value of urinary mevalonic acid measurement in patients with a clinical suspicion of mevalonate kinase deficiency. In this single-center, retrospective analysis, all patients in whom both measurement of mevalonic acid and genetic testing had been performed in the preceding 17 years have been included. The presence of two pathogenic MVK mutations or demonstration of decreased enzyme activity was considered to be the gold standard for the diagnosis of MKD. Sixty-one patients were included in this study. Thirteen of them harbored two MVK mutations; twelve of them showed elevated levels of mevalonic acid. Forty-eight patients did not harbor any MVK mutations, yet five of them excreted increased amounts of mevalonic acid. This corresponds to a sensitivity of 92%, a specificity of 90%, a positive predictive value of 71%, and a negative predictive value of 98%. The positive likelihood ratio is 10 and the negative likelihood ratio is 0.09. MKD seems very unlikely in patients with a normal mevalonic acid excretion, but it cannot be excluded completely. Further, a positive urinary mevalonic acid excretion still requires MVK analysis to confirm the diagnosis of MKD. Therefore, detection of urinary mevalonic acid should not be mandatory before genetic testing. However, as long as genetic testing is not widely available and affordable, measurement of urinary mevalonic acid is a fair way to select patients for MVK gene analysis or enzyme assay.

Long-term impact of systolic blood pressure and glycemia on the development of microalbuminuria in essential hypertension.

PubMed

Pascual, Jose Maria; Rodilla, Enrique; Gonzalez, Carmen; Pérez-Hoyos, Santiago; Redon, Josep

2005-06-01

The objective was to assess the temporal impact of factors related to the development of microalbuminuria during the follow-up of young adult normoalbuminurics with high-normal blood pressure or at stage 1 of essential hypertension. Prospective follow-up was conducted on 245 normoalbuminuric hypertensive subjects (mean age 40.9 years; 134 men; blood pressure 139.7/88.6 mm Hg; body mass index 28.5 kg/m2) never treated previously with antihypertensive drugs, with yearly urinary albumin excretion measurements, until the development of microalbuminuria. After enrollment, patients were placed on usual care including nonpharmacological treatment or with an antihypertensive drug regime to achieve a blood pressure of <135/85 mm Hg. Thirty subjects (12.2%) developed microalbuminuria after a mean follow-up of 29.9 months (range 12 to 144 months), 2.5 per 100 patients per year. Baseline urinary albumin excretion (hazard ratio, 1.07; P=0.006) and systolic blood pressure during the follow-up (hazard ratio, 1.03; P=0.008) were independent factors related to the follow-up urinary albumin excretion in a Cox proportional hazard model. A significant increase in the risk of developing microalbuminuria for urinary albumin excretion at baseline >15 mg per 24-hour systolic blood pressure >139 mm Hg and a positive trend in fasting glucose were observed in the univariate analyses. However, in the multivariate analysis, only the baseline urinary albumin excretion and the trend of fasting glucose were independently related to the risk of developing microalbuminuria. In mild hypertensives, the development of microalbuminuria was linked to insufficient blood pressure control and to a progressive increment of glucose values.

Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans: randomised, controlled trials.

PubMed

Larsen, Emil List; Cejvanovic, Vanja; Kjaer, Laura Kofoed; Pedersen, Morten Thorup; Popik, Sara Daugaard; Hansen, Lina Kallehave; Andersen, Jon Traerup; Jimenez-Solem, Espen; Broedbaek, Kasper; Petersen, Morten; Weimann, Allan; Henriksen, Trine; Lykkesfeldt, Jens; Torp-Pedersen, Christian; Poulsen, Henrik Enghusen

2017-08-01

In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs. This study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively. Clarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6-40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7-26.1%). Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7% (95% CI: 5.8-37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde. Clarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications. © 2017 The British Pharmacological Society.

Urinary excretion of uric acid is negatively associated with albuminuria in patients with chronic kidney disease: a cross-sectional study.

PubMed

Li, Fengqin; Guo, Hui; Zou, Jianan; Chen, Weijun; Lu, Yijun; Zhang, Xiaoli; Fu, Chensheng; Xiao, Jing; Ye, Zhibin

2018-04-24

Increasing evidence has shown that albuminuria is related to serum uric acid. Little is known about whether this association may be interrelated via renal handling of uric acid. Therefore, we aim to study urinary uric acid excretion and its association with albuminuria in patients with chronic kidney disease (CKD). A cross-sectional study of 200 Chinese CKD patients recruited from department of nephrology of Huadong hospital was conducted. Levels of 24 h urinary excretion of uric acid (24-h Uur), fractional excretion of uric acid (FEur) and uric acid clearance rate (Cur) according to gender, CKD stages, hypertension and albuminuria status were compared by a multivariate analysis. Pearson and Spearman correlation and multiple regression analyses were used to study the correlation of 24-h Uur, FEur and Cur with urinary albumin to creatinine ratio (UACR). The multivariate analysis showed that 24-h Uur and Cur were lower and FEur was higher in the hypertension group, stage 3-5 CKD and macro-albuminuria group (UACR> 30 mg/mmol) than those in the normotensive group, stage 1 CKD group and the normo-albuminuria group (UACR< 3 mg/mmol) (all P < 0.05). Moreover, males had higher 24-h Uur and lower FEur than females (both P < 0.05). Multiple linear regression analysis showed that UACR was negatively associated with 24-h Uur and Cur (P = 0.021, P = 0.007, respectively), but not with FEur (P = 0.759), after adjusting for multiple confounding factors. Our findings suggested that urinary excretion of uric acid is negatively associated with albuminuria in patients with CKD. This phenomenon may help to explain the association between albuminuria and serum uric acid.

Role of renal metabolism and excretion in 5-nitrofuran-induced uroepithelial cancer in the rat.

PubMed Central

Spry, L A; Zenser, T V; Cohen, S M; Davis, B B

1985-01-01

5-Nitrofurans have been used in the study of chemical carcinogenesis. There is substantial evidence that N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) is deformylated to 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) in the process of FANFT-induced bladder cancer. Paradoxically, ANFT is less potent as a uroepithelial carcinogen than FANFT when fed to rats. Feeding aspirin with FANFT to rats decreases the incidence of bladder cancer. Isolated kidneys were perfused with 5-nitrofurans to determine renal clearances and whether aspirin acts to decrease urinary excretion of the carcinogen. In FANFT-perfused kidneys, FANFT was deformylated to ANFT and excreted (1.06 +/- 0.22 nmol/min) at a rate eightfold higher than excretion of FANFT. In kidneys perfused with equimolar ANFT, excretion of ANFT was 0.25 +/- 0.05 nmol/min, which suggests a coupling of renal deformylation of FANFT to excretion of ANFT in FANFT-perfused kidneys. Neither aspirin nor probenecid altered the urinary excretion or half-life of FANFT or ANFT. In rats fed 0.2% FANFT as part of their diet, coadministration of aspirin (0.5%) increased urinary excretion of ANFT during a 12-wk feeding study, which suggests decreased tissue binding or metabolism of ANFT. Kidney perfusion with acetylated ANFT (NFTA), a much less potent uroepithelial carcinogen, resulted in no ANFT excretion or accumulation, which indicates the specificity of renal deformylase. Renal deformylase activity was found in broken cell preparations of rat and human kidney. These data describe a unique renal metabolic/excretory coupling for these compounds that appears to explain the differential carcinogenic potential of the 5-nitrofurans tested. These results are consistent with the hypothesis that aspirin decreases activation of ANFT by inhibiting prostaglandin H synthase. PMID:4044826

GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.

PubMed

Duann, Pu; Lianos, Elias A

2009-09-01

Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-beta1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury.

GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury

PubMed Central

Duann, Pu; Lianos, Elias A.

2009-01-01

Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-β1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury. PMID:19587144

Novel evidence that nitric oxide of the medial septal area influences the salivary secretion induced by pilocarpine.

PubMed

Saad, Wilson Abrão; Guarda, Ismael Francisco Motta Siqueira; Camargo, Luiz Antonio de Arruda; dos Santos, Talmir Augusto Faria Brisola; Saad, William Abrão; Simões, Sylvio; Guarda, Renata Saad

2002-04-05

Our studies have focused on the effect of injection of L-NAME and sodium nitroprussiate (SNP) on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine which was injected into the medial septal area (MSA). Rats were anesthetized with urethane (1.25 g/kg b. wt.) and a stainless steel cannula was implanted into their MSA. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into MSA. Injection of pilocarpine (10, 20, 40, 80, 160 microg/microl) into MSA produced a dose-dependent increase in salivary secretion. L-NG-nitro arginine methyl-esther (L-NAME) (40 microg/microl), a nitric oxide (NO) synthase inhibitor, was injected into MSA prior to the injection of pilocarpine into MSA, producing an increase in salivary secretion due to the effect of pilocarpine. Sodium nitroprussiate (SNP) (30 microg/microl) was injected into MSA prior to the injection of pilocarpine into MSA attenuating the increase in salivary secretion induced by pilocarpine. Medial arterial pressure (MAP) increase after injections of pilocarpine into the MSA. L-NAME injected into the MSA prior to injection of pilocarpine into MSA increased the MAP. SNP injected into the MSA prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (40 ug/ul) injected into the MAS induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the MSA increased the urinary sodium excretion and urinary volume induced by pilocarpine. SNP injected prior to pilocarpine into the MSA decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the MSA. We may also conclude that the MSA is involved with the cholinergic excitatory mechanism that induce salivary secretion, increase in MAP and increase in sodium excretion and urinary volume.

In vivo measurement of human body composition

NASA Technical Reports Server (NTRS)

Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Price, D. C.

1974-01-01

The female bed rest study has shown that, the response of women to prolonged recumbency of 2 to 3 weeks duration is very similar to that displayed by men. Some of the key findings in the women after 17 days of continuous recumbency are: (1) a decrease in plasma volume of 12-13 per cent; (2) a small decrease in total body water; (3) a decrease in total body potassium of 3 to 4 per cent; (4) a decrease in plasma potassium concentration of 4 to 5 per cent; (5) a decrease in total circulating plasma protein of 11 to 12 per cent; (6) a decrease in urinary norepinephrine excretion rate of 27 to 28 per cent; (7) a possible increase in urinary magnesium, calcium, and phosphate excretion rates; and (8) a possible increase in urinary citrate excretion rate.

Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease

PubMed Central

Mills, Katherine T.; Chen, Jing; Yang, Wei; Appel, Lawrence J.; Kusek, John W.; Alper, Arnold; Delafontaine, Patrice; Keane, Martin G.; Mohler, Emile; Ojo, Akinlolu; Rahman, Mahboob; Ricardo, Ana C.; Soliman, Elsayed Z.; Steigerwalt, Susan; Townsend, Raymond; He, Jiang

2016-01-01

IMPORTANCE Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. OBJECTIVE To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. EXPOSURES The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. MAIN OUTCOMES AND MEASURES A composite of CVD events defined as congestive heart failure, stroke, ormyocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. RESULTS Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09–1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03–1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08–3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001). CONCLUSIONS AND RELEVANCE Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD. PMID:27218629

Impact of Dietary Calcium and Oxalate, and Oxalobacter Formigenes Colonization on Urinary Oxalate Excretion

PubMed Central

Jiang, Juquan; Knight, John; Easter, Linda H.; Neiberg, Rebecca; Holmes, Ross P.; Assimos, Dean G.

2011-01-01

Purpose Enteric colonization with Oxalobacter formigenes, a bacterium whose main energy source is oxalate, has been demonstrated to decrease the risk of recurrent calcium oxalate kidney stone formation. We assessed the impact of diets controlled in calcium and oxalate contents on urinary and fecal analytes in healthy subjects who were naturally colonized with O. formigenes or not colonized with O. formigenes. Materials and Methods A total of 11 O. formigenes colonized and 11 noncolonized subjects were administered diets controlled in calcium and oxalate contents. We assayed 24-hour urine collections and stool samples obtained on the last 4 days of each 1-week diet for stone risk parameters and O. formigenes levels. Mixed model analysis was used to determine the effects of colonization status on these variables. Results Urinary calcium and oxalate excretion were significantly altered by the dietary changes in O. formigenes colonized and noncolonized individuals. Mixed model analysis showed significant interaction between colonization status and oxalate excretion on a low calcium (400 mg daily)/moderate oxalate (250 mg daily) diet (p = 0.026). Urinary oxalate excretion was 19.5% lower in O. formigenes colonized subjects than in noncolonized subjects on the low calcium/moderate oxalate diet (mean ± SE 34.9 ± 2.6 vs 43.6 ± 2.6 mg, p = 0.031). Conclusions Results suggest that O. formigenes colonization decreases oxalate excretion during periods of low calcium and moderate oxalate intake. PMID:21575973

Urinary excretion of uranium in adult inhabitants of the Czech Republic.

PubMed

Malátová, Irena; Bečková, Věra; Kotík, Lukáš

2016-02-01

The main aim of this study was to determine and evaluate urinary excretion of uranium in the general public of the Czech Republic. This value should serve as a baseline for distinguishing possible increase in uranium content in population living near legacy sites of mining and processing uranium ores and also to help to distinguish the proportion of the uranium content in urine among uranium miners resulting from inhaled dust. The geometric mean of the uranium concentration in urine of 74 inhabitants of the Czech Republic was 0.091 mBq/L (7.4 ng/L) with the 95% confidence interval 0.071-0.12 mBq/L (5.7-9.6 ng/L) respectively. The geometric mean of the daily excretion was 0.15 mBq/d (12.4 ng/d) with the 95% confidence interval 0.12-0.20 mBq/d (9.5-16.1 ng/d) respectively. Despite the legacy of uranium mines and plants processing uranium ore in the Czech Republic, the levels of uranium in urine and therefore, also human body content of uranium, is similar to other countries, esp. Germany, Slovenia and USA. Significant difference in the daily urinary excretion of uranium was found between individuals using public supply and private water wells as a source of drinking water. Age dependence of daily urinary excretion of uranium was not found. Mean values and their range are comparable to other countries, esp. Germany, Slovenia and USA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Urinary sodium and potassium excretion, mortality, and cardiovascular events.

PubMed

O'Donnell, Martin; Mente, Andrew; Rangarajan, Sumathy; McQueen, Matthew J; Wang, Xingyu; Liu, Lisheng; Yan, Hou; Lee, Shun Fu; Mony, Prem; Devanath, Anitha; Rosengren, Annika; Lopez-Jaramillo, Patricio; Diaz, Rafael; Avezum, Alvaro; Lanas, Fernando; Yusoff, Khalid; Iqbal, Romaina; Ilow, Rafal; Mohammadifard, Noushin; Gulec, Sadi; Yusufali, Afzal Hussein; Kruger, Lanthe; Yusuf, Rita; Chifamba, Jephat; Kabali, Conrad; Dagenais, Gilles; Lear, Scott A; Teo, Koon; Yusuf, Salim

2014-08-14

The optimal range of sodium intake for cardiovascular health is controversial. We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome. In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).

Urinary levels of nickel and chromium associated with dental restoration by nickel–chromium based alloys

PubMed Central

Chen, Bo; Xia, Gang; Cao, Xin-Ming; Wang, Jue; Xu, Bi-Yao; Huang, Pu; Chen, Yue; Jiang, Qing-Wu

2013-01-01

This paper aims to investigate if the dental restoration of nickel–chromium based alloy (Ni–Cr) leads to the enhanced excretions of Ni and Cr in urine. Seven hundred and ninety-five patients in a dental hospital had single or multiple Ni–Cr alloy restoration recently and 198 controls were recruited to collect information on dental restoration by questionnaire and clinical examination. Urinary concentrations of Ni and Cr from each subject were measure by graphite furnace atomic absorption spectrometry. Compared to the control group, the urinary level of Ni was significantly higher in the patient group of <1 month of the restoration duration, among which higher Ni excretions were found in those with either a higher number of teeth replaced by dental alloys or a higher index of metal crown not covered with the porcelain. Urinary levels of Cr were significantly higher in the three patient groups of <1, 1 to <3 and 3 to <6 months, especially in those with a higher metal crown exposure index. Linear curve estimations showed better relationships between urinary Ni and Cr in patients within 6-month groups. Our data suggested significant increased excretions of urinary Ni and Cr after dental restoration. Potential short- and long-term effects of Ni–Cr alloy restoration need to be investigated. PMID:23579466

Urinary corticosterone metabolite responses to capture and captivity in the cane toad (Rhinella marina).

PubMed

Narayan, Edward J; Cockrem, John F; Hero, Jean-Marc

2011-09-01

Urinary corticosterone metabolite responses to capture have recently been shown for the first time in amphibians, and in the present study urinary corticosterone metabolite responses to capture and to confinement in captivity were measured in adult cane toads (Rhinella marina) in Queensland, Australia. An adrenocorticotropic hormone (ACTH) challenge was used to provide a biological validation for urinary corticosterone metabolite concentrations measured by radioimmunoassay (RIA). Urinary corticosterone metabolite increased 1-2 days after ACTH but not saline injection and then returned to initial values, indicating that the RIA could detect changes in corticosterone secretion in toads. Urinary corticosterone metabolite responses to short-term capture and restraint in plastic bags were first apparent 2h after capture of wild toads. Toads held communally in captivity for 5 days had elevated urinary corticosterone metabolite concentrations. Mean corticosterone concentrations declined significantly after a further 7 days in individual housing chambers. There was no sex difference in urinary corticosterone metabolite responses of toads to ACTH challenge, short-term capture or captivity. The relative amount of variation in the mean corticosterone responses was quantified by calculating coefficients of variation (CV) for each mean corticosterone response. Mean corticosterone at 0 min was more variable for captive toads than wild toads. Furthermore, initial corticosterone concentrations (0 min) were more variable than concentrations during the ACTH challenge, short-term capture and captivity. There was little change in the amount of variation of mean corticosterone levels between male and female toads with increasing time in captivity (12-29 days). This study has shown individual corticosterone responses of amphibians for the first-time, and has provided a novel method for quantifying the relative amount of variation in amphibian corticosterone responses. Copyright © 2011 Elsevier Inc. All rights reserved.

Urinary excretion of orally ingested gastrografin on CT.

PubMed

Apter, S; Gayer, G; Amitai, M; Hertz, M

1998-01-01

Renal excretion of orally ingested gastrografin has rarely been reported on computed tomography (CT). We studied the unenhanced scans of 82 patients with bowel disorders or perforation to assess the prevalence of urinary contrast material (CM) in various bowel diseases. We also assessed the clinical significance of this sign. In addition, we reviewed the unenhanced CT scans of 100 randomly selected patients without bowel diseases as a control group. Twenty-nine of the 58 patients with bowel diseases, six of nine with free perforation, and one of 15 with covered perforation had CM in the urinary tract. None of the 100 without bowel disease showed urinary CM. Statistical analysis was done by using the Fisher's exact test. The prevalence of urinary CM was highest in inflammatory bowel disease, radiation enteritis, and free perforation (p < 0. 0001). This study shows that the CT finding of orally ingested gastrografin in the urinary tract differentiates patients with bowel disease from those without.

Eight hours of nocturnal 915 MHz radiofrequency identification (RFID) exposure reduces urinary levels of melatonin and its metabolite via pineal arylalkylamine N-acetyltransferase activity in male rats.

PubMed

Kim, Hye Sun; Paik, Man-Jeong; Lee, Yu Hee; Lee, Yun-Sil; Choi, Hyung Do; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

2015-01-01

We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on melatonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT). Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Urinary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively. Eight hours of nocturnal RFID exposure caused a significant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expression of AANAT were suppressed by exposure to RFID (p < 0. 05). Our results suggest that nocturnal RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression of Aanat gene transcription in the rat pineal gland.

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

PubMed Central

Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

2016-01-01

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Medeiros, Pedro Bettencourt; Santos, Mário; Carvalho, Henrique Cyrne; Bettencourt, Paulo; Kénizou, David; Butler, Javed; Zannad, Faiez; Rossignol, Patrick

2016-06-01

Loop diuretic resistance characterized by inefficient sodium excretion complicates many patients with acutely decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) in natriuretic doses may improve spot urine sodium excretion and outcomes. Our primary aim was to assess the association of high-dose spironolactone with short-term spot urine sodium excretion, and our secondary aim was to determine if this higher short-term spot urine sodium excretion is associated with reduction in the composite clinical outcome (of cardiovascular mortality and/or ADHF hospitalization) event rate at 180 days. Single-centre, non-randomized, open-label study enrolling 100 patients with ADHF. Patients were treated with standard ADHF therapy alone (n = 50) or oral spironolactone 100 mg/day plus standard ADHF therapy (n = 50). Spot urine samples were collected at day 1 and day 3 of hospitalization. Spironolactone group had significantly higher spot urine sodium levels compared to standard care group at day 3 (84.13 ± 28.71 mmol/L vs 70.74 ± 34.43 mmol/L, p = 0.04). The proportion of patients with spot urinary sodium <60 mmol/L was lower in spironolactone group at day 3 (18.8 vs 45.7, p = 0.01). In multivariate analysis, spironolactone was independently associated with increased spot urinary sodium and urinary sodium/potassium ratio of >2 at day 3 (both, p < 0.05). Higher spot urine sodium levels were associated with a lower event rate [HR for urinary sodium >100 mmol/L = 0.16 (0.06-0.42), p < 0.01, compared to <60], and provided a significant prognostic gain measured by net reclassification indexes. Spot urinary sodium levels >60 mmol/L and urinary sodium/potassium ratio >2 measured at day 3 of hospitalization for ADHF are associated with improved mid-term outcomes. Spironolactone is associated with increased spot urinary sodium and sodium/potassium ratio >2.

Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury.

PubMed

Kim, Kyeong Seok; Yang, Hun Yong; Song, Hosup; Kang, Ye Rim; Kwon, JiHoon; An, JiHye; Son, Ji Yeon; Kwack, Seung Jun; Kim, Young-Mi; Bae, Ok-Nam; Ahn, Mee-Young; Lee, Jaewon; Yoon, Sungpil; Lee, Byung Mu; Kim, Hyung Sik

2017-01-01

Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.

Comparison of two aquaretic drugs (niravoline and OPC-31260) in cirrhotic rats with ascites and water retention.

PubMed

Bosch-Marcé, M; Poo, J L; Jiménez, W; Bordas, N; Leivas, A; Morales-Ruiz, M; Muñoz, R M; Pérez, M; Arroyo, V; Rivera, F; Rodés, J

1999-04-01

kappa-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic administration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine volume, urinary osmolality, sodium excretion, and urinary excretion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increased water excretion, peripheral resistance, serum osmolality, and sodium excretion and reduced creatinine clearance, ALD and ADH excretion, and mRNA expression of ADH. OPC-31260 also increased water metabolism and sodium excretion and reduced urinary ALD, although the aquaretic effect was only evident during the first 2 days, and no effects on serum osmolality, renal filtration, and systemic hemodynamics were observed. Therefore, both agents have aquaretic efficacy, but the beneficial therapeutic effects of the long-term oral administration of niravoline are more consistent than those of OPC-31260 in cirrhotic rats with ascites and water retention.

Effects of exercise on the urinary proteome.

PubMed

Kohler, Maxie; Schänzer, Wilhelm; Thevis, Mario

2015-01-01

Exercise-induced proteinuria has been observed and studied for more than a century. It was found that different sport disciplines alter the urinary proteome in different ways. Moderate-intensity exercise results in increased glomerular filtration, meaning that medium-sized proteins are excreted in higher amounts, while high-intensity exercise of short duration also increases the excretion of low molecular weight proteins as a result of tubular dysfunction. Exhaustive exercise may lead to the excretion of hemoglobin or myoglobin, which changes the urinary proteome considerably. Studies comparing protein maps of different sport types compared to a control group showed that quality and quantity of urinary proteins are interindividually different. In addition, urine samples collected before and after exercise exhibit substantially different protein patterns even from the same person. Therefore, further studies investigating the urinary proteome are desirable. As the variation of protein content and composition in urine are generally much higher than in other matrices, respective studies need to be well controlled and homogenous groups of volunteers should be chosen. In addition to the sport-related physiological and biochemical interest, exercise-induced protein changes also need to be considered for biomarker measurements from urine samples for kidney or other diseases.

Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects.

PubMed

Tang, Minghua; Larson-Meyer, D Enette; Liebman, Michael

2008-05-01

High oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. This study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. Eleven healthy subjects, aged 21-38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. Compared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. The percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.

Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia.

PubMed

Zhang, Yi; Jin, Lijun; Liu, Jinchang; Wang, Wei; Yu, Haiyang; Li, Jian; Chen, Qian; Wang, Tao

2018-03-25

Dioscin, a spirostane glycoside, the rhizoma of Dioscorea septemloba (Diocoreacea) is used for diuresis, rheumatism, and joints pain. Given the poor solubility and stability of Dioscin, we proposed a hypothesis that Dioscin's metabolite(s) are the active substance(s) in vivo to contribute to the reducing effects on serum uric acid levels. The aim of this study is to identify the active metabolite(s) of Dioscin in vivo and to explore the mechanism of its antihyperuricemic activity. After oral administration of Dioscin in potassium oxonate (PO) induced hyperuricemia rats and adenine-PO induced hyperuricemia mice models, serum uric acid and creatinine levels, clearance of uric acid and creatinine, fractional excretion of uric acid, and renal pathological lesions were determined were used to evaluate the antihyperuricemic effects. Renal glucose transporter-9 (GLUT-9) and organic anion transporter-1 (OAT-1) expressions were analyzed by western blotting method. Renal uric acid excretion was evaluated using stably urate transporter-1 (URAT-1) transfected human epithelial kidney cell line. Intestinal uric acid excretion was evaluated by measuring the transcellular transport of uric acid in HCT116 cells. In hyperuricemia rats, both 25 and 50mg/kg of oral Dioscin decreased serum uric acid levels over 4h. In the hyperuricemia mice, two weeks treatment of Dioscin significantly decreased serum uric acid and creatinine levels, increased clearance of uric acid and creatinine, increased fractional excretion of uric acid, and reduced renal pathological lesions caused by hyperuricemia. In addition, renal GLUT -9 was significantly down-regulated and OAT-1 was up-regulated in Dioscin treated hyperuricemia mice. Dioscin's metabolite Tigogenin significantly inhibited uric acid re-absorption via URAT1 from 10 to 100μM. Diosgenin and Tigogenin increased uric acid excretion via ATP binding cassette subfamily G member 2 (ABCG2). Decreasing effect of Dioscin on serum uric acid level and enhancing effect on urate excretion were confirmed in hyperuricemia animal models. Tigogenin, a metabolite of Dioscin, was identified as an active substance with antihyperuricemic activity in vivo, through inhibition of URAT1 and promotion of ABCG2. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

PubMed

Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

2016-01-01

Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible. Deconjugation (mediated by hydrolases) plays an essential role in the conjugation-transport interplay. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil.

PubMed

D'Angelo, S; Manna, C; Migliardi, V; Mazzoni, O; Morrica, P; Capasso, G; Pontoni, G; Galletti, P; Zappia, V

2001-11-01

3,4-Dihydroxyphenylethanol (DOPET) is the major o-diphenol detectable in extra virgin olive oil, either in free or esterified form. Despite its relevant biological effects, mainly related to its antioxidant properties, little data have been reported so far on its toxicity and metabolism. The aim of the present work is to evaluate DOPET toxicity and to investigate its molecular pharmacokinetics by using the (14)C-labeled diphenol. When orally administered to rats, the molecule does not show appreciable toxicity up to 2 g/kg b.wt. To identify and quantify its metabolites, [(14)C]DOPET has been synthesized and intravenously injected in rats. The pharmacokinetic analysis indicates a fast and extensive uptake of the molecule by the organs and tissues investigated, with a preferential renal uptake. Moreover, 90% of the administered radioactivity is excreted in urine collected up to 5 h after injection, and about 5% is detectable in feces and gastrointestinal content. The characterization of the labeled metabolites, extracted from the organs and urine, has been performed by high-pressure liquid chromatography analysis. In all the investigated tissues, DOPET is enzymatically converted in four oxidized and/or methylated derivatives. Moreover, a significant fraction of total radioactivity is associated with the sulfo-conjugated forms, which also represent the major urinary excretion products. On the basis of the reported results, an intracellular metabolic pathway of exogenously administered DOPET, implying the involvement of catechol-O-methyltransferase, alcohol dehydrogenase, aldehyde dehydrogenase, and phenolsulfotransferase, has been proposed.

Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

PubMed Central

Zou, Peng; Helson, Lawrence; Maitra, Anirban; Stern, Stephan T.; McNeil, Scott E.

2013-01-01

The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle encapsulated (nanocurcumin), and solvent solubilized curcumin formulations in Sprague Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon i.v. administration of nanocurcumin only nanoparticle encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile, but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested rapid, “burst” release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations. PMID:23534919

Phenytoin pharmacokinetics in critically ill trauma patients.

PubMed

Boucher, B A; Rodman, J H; Jaresko, G S; Rasmussen, S N; Watridge, C B; Fabian, T C

1988-12-01

Preliminary data have suggested that phenytoin systemic clearance may increase during initial therapy in critically ill patients. The objectives for this study were to model the time-variant phenytoin clearance and evaluate concomitant changes in protein binding and urinary metabolite elimination. Phenytoin was given as an intravenous loading dose of 15 mg/kg followed by an initial maintenance dose of 6 mg/kg/day in 10 adult critically ill trauma patients. Phenytoin bound and unbound plasma concentrations were determined in 10 patients and urinary excretion of the metabolite p-hydroxyphenyl phenylhydantoin (p-HPPH) was measured in seven patients for 7 to 14 days. A Michaelis-Menten one-compartment model incorporating a time-variant maximal velocity (Vmax) was sufficient to describe the data and superior to a conventional time-invariant Michaelis-Menten model. Vmax for the time-variant model was defined as V'max + Vmax delta (1 - e(-kindt)). Vmax infinity is the value for Vmax when t is large. The median values (ranges) for the parameters were Km = 4.8 (2.6 to 20) mg/L, Vmax infinity = 1348 (372 to 4741) mg/day, and kind = 0.0115 (0.0045 to 0.132) hr-1. Phenytoin free fraction increased in a majority of patients during the study period, with a binding ratio inversely related to albumin. Measured urinary p-HPPH data were consistent with the proposed model. A loading and constant maintenance dose of phenytoin frequently yielded a substantial, clinically significant fall in plasma concentrations with a pattern of apparently increasing clearance that may be a consequence of changes in protein binding, induction of metabolism, or the influence of stress on hepatic metabolic capacity.

Aronia berry polyphenol consumption reduces plasma total and low-density lipoprotein cholesterol in former smokers without lowering biomarkers of inflammation and oxidative stress: a randomized controlled trial.

PubMed

Xie, Liyang; Vance, Terrence; Kim, Bohkyung; Lee, Sang Gil; Caceres, Christian; Wang, Ying; Hubert, Patrice A; Lee, Ji-Young; Chun, Ock K; Bolling, Bradley W

2017-01-01

Former smokers are at increased risk for cardiovascular disease. We hypothesized that dietary aronia polyphenols would reduce biomarkers of cardiovascular disease risk, inflammation, and oxidative stress in former smokers. We also determined the extent these effects were associated with polyphenol bioavailability. A 12-week, randomized, placebo-controlled trial was conducted in 49 healthy adult former smokers (n = 24/placebo, n = 25/aronia) to evaluate if daily consumption of 500 mg aronia extract modulated plasma lipids, blood pressure, biomarkers of inflammation and oxidative stress, and lipid transport genes of peripheral blood mononuclear cells. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C) from baseline, and multivariate correlation analysis was performed to determine if changes in lipids were associated with urinary polyphenol excretion. Aronia consumption reduced fasting plasma total cholesterol by 8% (P = .0140), LDL-C by 11% (P = .0285), and LDL receptor protein in peripheral blood mononuclear cells (P = .0036) at 12 weeks compared with the placebo group. Positive changes in the urinary polyphenol metabolites peonidin-3-O-galactoside, 3-(4-hydroxyphenyl) propionic acid, and unmetabolized anthocyanin cyanidin-3-O-galactoside were associated with lower plasma total cholesterol and LDL-C in the aronia group. Aronia consumption did not change blood pressure or biomarkers of inflammation and oxidative stress. Aronia polyphenols reduced total and LDL-C in former smokers but did not improve biomarkers of oxidative stress and chronic inflammation. The cholesterol-lowering activity of aronia extract was most closely associated with urinary levels of cyanidin-3-O-galactoside and peonidin-3-O-galactoside, its methylated metabolite. This trial was registered at ClinicalTrials.gov as NCT01541826. Copyright © 2016 Elsevier Inc. All rights reserved.

Sodium and potassium urinary excretion levels of preschool children: Individual, daily, and seasonal differences.

PubMed

Yasutake, Kenichiro; Nagafuchi, Mikako; Izu, Ryoji; Kajiyama, Tomomi; Imai, Katsumi; Murata, Yusuke; Ohe, Kenji; Enjoji, Munechika; Tsuchihashi, Takuya

2017-06-01

In this study, the authors measured sodium and potassium concentrations in spot urine samples of preschool children on multiple days, and evaluated individual, daily, and seasonal effects. A total of 104 healthy preschool children aged 4 to 5 years were studied. Urine samples were collected from the first urine of the day after waking for three consecutive days (Monday-Wednesday) four times a year (spring, summer, autumn, winter). The authors estimated the daily urine volume as 500 mL and daily creatinine excretion as 300 mg, and used these to calculate daily sodium and potassium excretion levels. Daily sodium and potassium excretion levels and sodium to potassium ratios were highly variable. The coefficient variant in the children's excretion levels were also high within and between individuals. Sodium excretion levels and sodium to potassium ratios were higher on Monday (weekend sodium intakes) than Tuesday. Season had no effect on sodium or potassium excretion levels, but the sodium to potassium ratio was higher in summer than in winter. In conclusion, levels of urinary sodium excretion are comparatively high and those of potassium are low in preschool students, with high variability within and between individuals. ©2017 Wiley Periodicals, Inc.

Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat.

PubMed

Wang, Chong; Wang, Changyuan; Liu, Qi; Meng, Qiang; Cang, Jian; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Huo, Xiaokui; Liu, Kexin

2014-06-01

This study aimed to evaluate the transporter-mediated renal excretion mechanism for cilostazol and to characterize the mechanism of drug-drug interaction (DDI) between cilostazol and aspirin or probenecid. Concentrations of cilostazol and its metabolites OPC-13015 [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-2(1H)-quinolinone] and OPC-13213 [3,4-dihydro-6-[4-[1-(trans-4-hydroxycyclohexyl)-1H-tetrazol-5-yl]butoxy]-2-(1H)-quinolinone] in rat biologic or cell samples were measured by liquid chromatography-tandem mass spectrometry. Coadministration with probenecid, benzylpenicillin, or aspirin decreased the cumulative urinary excretion of cilostazol and renal clearance. Concentrations of cilostazol and OPC-13213 in plasma decreased, and the concentration of OPC-13015 increased in the presence of probenecid. By contrast, rat plasma cilostazol, in combination with benzylpenicillin or aspirin, sharply increased, and concentrations of OPC-13015 and OPC-13213 did not change. In urine, OPC-13015 was below the level of detection. The cumulative urinary excretion of OPC-13213 decreased in the presence of probenecid, benzylpenicillin, or aspirin. Cilostazol was distributed in the kidney and liver, with tissue to plasma partition coefficient (Kp) values of 8.4 ml/g and 16.3 ml/g, respectively. Probenecid and aspirin reduced cilostazol distribution in the kidney. Probenecid did not affect cilostazol metabolism in the kidney but increased cilostazol metabolism in the liver, and aspirin had no effect on cilostazol metabolism. Benzylpenicillin, aspirin, and cyclo-trans-4-l-hydroxyprolyl-l-serine (JBP485) reduced cilostazol uptake in kidney slices and human organic anion transporter 3 (hOAT3)-human embryonic kidney 293 (HEK293) cells, whereas p-aminohippuric acid did not. Compared with the vector, hOAT3-HEK293 cells accumulated more cilostazol, whereas hOAT1-HEK293 cells did not. OAT3 and Oat3 play a major role in cilostazol renal excretion, whereas OAT1 and Oat1 do not. Oat3 and Cyp3a are both targets of the DDI between cilostazol and probenecid. Aspirin inhibits OAT3-mediated uptake of cilostazol and does not influence cilostazol metabolism.

Reversibility of increased intestinal permeability to 51Cr-EDTA in patients with gastrointestinal inflammatory diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, R.T.; Jones, D.B.; Goodacre, R.L.

1987-11-01

Intestinal permeability in adults with inflammatory gastrointestinal diseases was investigated by measuring the 24-h urinary excretion of orally administered /sup 51/Cr-EDTA. Eighty controls along with 100 patients with Crohn's disease, 46 patients with ulcerative colitis, 20 patients with gluten-sensitive enteropathy, and 18 patients with other diseases were studied. In controls, the median 24-h excretion was 1.34%/24 h of the oral dose. Patients with Crohn's disease (median 2.96%/24 h), ulcerative colitis (median 2.12%/24 h), and untreated gluten-sensitive enteropathy (median 3.56%/24 h) had significantly elevated urinary excretion of the probe compared to controls (p less than 0.0001). Increased 24-h urinary excretion ofmore » /sup 51/Cr-EDTA had a high association with intestinal inflammation (p less than 0.0001). Test specificity and sensitivity were 96% and 57%, respectively. A positive test has a 96% probability of correctly diagnosing the presence of intestinal inflammation, whereas a negative test has a 50% probability of predicting the absence of disease.« less

Cortisol-mediated synchronization of circadian rhythm in urinary potassium excretion

NASA Technical Reports Server (NTRS)

Moore-Ede, M. C.; Schmelzer, W. S.; Kass, D. A.; Herd, J. A.

1977-01-01

Conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 hr daily (LD 12:12) display a prominent circadian rhythm in renal potassium excretion. The characteristics of this rhythm were reproduced in adrenalectomized monkeys by infusing 5 mg cortisol and 0.001 mg aldosterone, or 5 mg cortisol alone, between 0800 and 0900 kr daily. When the timing of cortisol administration (with or without aldosterone) was phase-delayed by 8 hr, the urinary potassium rhythm resynchronized by 80% of the cortisol phase shift, but only after a transient response lasting 3-4 days. With the same daily dose of adrenal steroids given as a continuous infusion throughout each 24 hr, urinary potassium excretion showed free-running oscillations no longer synchronized to the light-dark cycle. These results indicate that the circadian rhythm of plasma cortisol concentration acts as an internal mediator in the circadian timing system, synchronizing a potentially autonomous oscillation in renal potassium excretion to environmental time cues and to other circadian rhythms within the animal.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Dietary potassium intake and renal handling, and their impact on the cardiovascular health of normotensive afro-caribbeans.

PubMed

Cohall, D H; Scantlebury-Manning, T; Rafie, C; James, S; Hall, K

2014-01-01

Recent nutritional profiles of dietary intake have indicated a shift from the ancient diet to the Western diet. The ancient diet provided a high potassium and low sodium intake, which in turn leads to sodium conservation and potassium excretion. This change in the dietary intake is expected to affect potassium and sodium handling in the kidneys. Numerous studies have been done to emphasize the importance of sodium handling by the kidneys and its impact on cardiovascular health. This study will investigate potassium intake and handling, and its impact on the cardiovascular health of a sample of normotensive Afro-Caribbeans by the possible modulation of the renin angiotensin aldosterone system (RAAS). A sample of 51 normotensive Afro-Caribbean participants was recruited for the study. Participants were observed over a two-day period in which they were given a 24-hour ambulatory blood pressure monitor and a container to collect blood pressure data and a 24-hour urine sample. Anthropometric measurements were noted. Urinary electrolytes and supine plasma renin activity (PRA) were determined from the 24-hour urine collection and a blood sample. Dietary potassium intake was estimated based on dietary intake observations and calculated based on the urinary potassium excretion. SPSS version 19 was used to analyse the data to make inferences. The daily potassium intake was observed to be 2.95 g/day and measured intake from the urinary potassium was between 4.95 and 7.32 g/day. Urinary potassium excretion was 3.66 (± 1.40) g/day. The urinary potassium excretion in the Afro-Caribbean sample in Barbados was higher than the other population samples. The averaged PRA of the participants (supine) was 0.778 (± 1.072) ng/mL/hour. The averaged nocturnal systolic blood pressure dip of the participants was 5.97 (± 4.324) %. There was no significant correlation between urinary potassium excretion, blood pressure, nocturnal systolic blood pressure dip and PRA. The Afro-Caribbean sample has an inadequate daily potassium intake based on the observed intake and recommended values, with a high urinary excretion of the electrolyte compared to other values in the literature. This high potassium excretion could have been partly due to low plasma renin activity levels in the study participants. As a possible consequence, an increase in the nocturnal peripheral resistance is a likely cause for the diminished systolic dip. The lack of correlations between dietary potassium excretion and the blood pressure parameters does not allow any firm inference of the electrolyte's handling and its impact on cardiovascular health in the normotensive Afro-Caribbean participants. However, further research is needed to get a more accurate daily potassium intake value, and a more statistically robust sample to assess whether potassium handling and blood pressure would be affected by a change in potassium intake.

Excretion pattern of enrofloxacin after oral treatment of chicken broilers.

PubMed

Slana, M; Pahor, V; Cvitkovič Maričič, L; Sollner-Dolenc, M

2014-12-01

The metabolism and excretion of enrofloxacin were studied when applied as oral solution to chicken broilers for five consecutive days. Sixty 9-day-old broilers were isolated within an intensively rearing poultry farm during enrofloxacin therapy (15.5 mg/kg per day). The excreta of the isolated broilers were collected daily, 9 days after therapy termination, for 13 consecutive days, and analyzed for the presence of enrofloxacin and its metabolites [ciprofloxacin, desethylene-enrofloxacin (DES-EF) and desethylene-ciprofloxacin (DES-CF)]. Enrofloxacin was excreted predominantly in the form of the parent compound between days 1 and 13. Ciprofloxacin was detected in the excreta between days 1 and 6, whereas minor amounts of DES-EF and DES-CF were excreted only between days 1-7 and 1-6, respectively. In conclusion, the analysis of the excreta showed that approximately 74% of orally applied enrofloxacin was excreted as the parent compound, approximately 25% as the main metabolite ciprofloxacin, and approximately 1% as the minor metabolites desethylene-enrofloxacin and desethylene-ciprofloxacin. © 2014 John Wiley & Sons Ltd.

Hypertension increases urinary excretion of immunoglobulin G, ceruloplasmin and transferrin in normoalbuminuric patients with type 2 diabetes mellitus.

PubMed

Ohara, Nobumasa; Hanyu, Osamu; Hirayama, Satoshi; Nakagawa, Osamu; Aizawa, Yoshifusa; Ito, Seiki; Sone, Hirohito

2014-02-01

Increased urinary excretion of certain plasma proteins, such as immunoglobulin G (IgG), ceruloplasmin and transferrin, with different molecular radii of 55 Å or less and different isoelectric points have been reported to precede development of microalbuminuria in patients who have diabetes mellitus with hypertension. We examined how hypertension affects these urinary proteins in a diabetic state. Excretion of IgG, ceruloplasmin, transferrin, albumin, α2-macroglobulin with a large molecular radius of 88 Å and N-acetylglucosaminidase in first-morning urine samples were measured in normoalbuminuric patients (urinary albumin-to-creatinine ratio < 15 mg/g) with hypertension and nondiabetes mellitus (group hypertension, n = 32), type 2 diabetes mellitus and normotension (group diabetes mellitus, n = 52) and type 2 diabetes mellitus and hypertension (group Both, n =45), and in age-matched controls (n = 72). Urinary IgG, ceruloplasmin, transferrin, albumin and N-acetylglucosaminidase and estimated glomerular filtration rate (eGFR) were significantly elevated in groups diabetes mellitus and Both compared with controls. Furthermore, urinary IgG, ceruloplasmin and transferrin in group Both were significantly higher than those in group diabetes mellitus. These exhibited a positive and relatively strong association with eGFR compared with controls. No significant difference in urinary albumin or N-acetylglucosaminidase was found between the two diabetic groups. In contrast, group hypertension had elevated urinary transferrin without any changes in the other compounds. Urinary α2-macroglobulin did not differ among the four groups. These findings suggest that normoalbuminuric diabetic patients without hypertension have both glomerular hemodynamic changes such as increased intraglomerular hydraulic pressure and altered proximal tubules, and that hypertension increases intraglomerular hydraulic pressure. Increased urinary IgG, ceruloplasmin and transferrin may reflect an increase in intraglomerular hydraulic pressure.

Effect of acute hyperinsulinemia on magnesium homeostasis in humans.

PubMed

Xu, Li Hao Richie; Maalouf, Naim M

2017-02-01

Insulin may influence magnesium homeostasis through multiple mechanisms. Acutely, it stimulates the shift of magnesium from plasma into red blood cells and platelets, and in vitro, it stimulates the activity of the TRPM6 channel, a key regulator of renal magnesium reabsorption. We investigated the impact of hyperinsulinemia on magnesium handling in participants with a wide range of insulin sensitivity. Forty-seven participants were recruited, including 34 nondiabetic controls and 13 with type 2 diabetes mellitus. After stabilization under fixed metabolic diet, participants underwent hyperinsulinemic-euglycemic clamp. Serum and urine samples were collected before and during hyperinsulinemia. Change in serum magnesium, urinary magnesium to creatinine (Mg 2 + :Cr) ratio, fractional excretion of urinary magnesium (FEMg 2 + ), and estimated transcellular shift of magnesium were compared before and during hyperinsulinemia. Hyperinsulinemia led to a small but statistically significant decrease in serum magnesium, and to a shift of magnesium into the intracellular compartment. Hyperinsulinemia did not significantly alter urinary magnesium to creatinine ratio or fractional excretion of urinary magnesium in the overall population, although a small but statistically significant decline in these parameters occurred in participants with diabetes. There was no significant correlation between change in fractional excretion of urinary magnesium and body mass index or insulin sensitivity measured as glucose disposal rate. In human participants, acute hyperinsulinemia stimulates the shift of magnesium into cells with minimal alteration in renal magnesium reabsorption, except in diabetic patients who experienced a small decline in fractional excretion of urinary magnesium. The magnitude of magnesium shift into the intracellular compartment in response to insulin does not correlate with that of insulin-stimulated glucose entry into cells. Copyright © 2016 John Wiley & Sons, Ltd.

Urinary oxalate to creatinine ratios in healthy Turkish schoolchildren

PubMed Central

Dursun, Ismail; Çelik, İlknur; Poyrazoglu, Hakan M.; Tanrıkulu, Esen; Sahin, Habibe; Yılmaz, Kenan; Öztürk, Ahmet; Yel, Sibel; Gündüz, Zübeyde; Düşünsel, Ruhan

2017-01-01

Abstract Aim: we aimed to establish reference values for urinary oxalate to creatinine ratios in healthy children aged 6–15 years and to investigate the relationship between their nutritional habits and oxalate excretion. Materials and methods: Random urine specimens from 953 healthy children aged 6–15 years were obtained and analyzed for oxalate and creatinine. Additionally, a 24-h dietary recall form was prepared and given to them. The ingredient composition of the diet was calculated. The children were divided into three groups according to age: Group I (69 years, n = 353), Group II (10–12 years, n = 335), and Group III (13–15 years, n = 265). Results: The 95th percentile of the oxalate to creatinine ratio for subjects aged 6–9, 10–12, and 13–15 years were 0.048, 0.042, and 0.042 mg/mg, respectively. The oxalate to creatinine ratio was significantly higher in Group 1 than in Group 2 and Group 3. Urinary oxalate excretion was positively correlated with increased protein intake and negatively correlated with age. A significant positive correlation was determined between urinary oxalate excretion and the proline, serine, protein, and glycine content of diet. Dietary proline intake showed a positive correlation with the urine oxalate to creatinine ratio and was found to be an independent predictor for urinary oxalate. Conclusions: These data lend support to the idea that every country should have its own normal reference values to determine the underlying metabolic risk factor for kidney stone disease since regional variation in the dietary intake of proteins and other nutrients can affect normal urinary excretion of oxalate. PMID:27846788

Estimating 24-Hour Urinary Sodium Excretion From Casual Urinary Sodium Concentrations in Western Populations

PubMed Central

Brown, Ian J.; Dyer, Alan R.; Chan, Queenie; Cogswell, Mary E.; Ueshima, Hirotsugu; Stamler, Jeremiah; Elliott, Paul

2013-01-01

High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984–1987 at the ages of 20–59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were −1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and −1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity. PMID:23673246

Hypophosphatemic rickets with hypocalciuria following long-term treatment with aluminum-containing antacid.

PubMed

Foldes, J; Balena, R; Ho, A; Parfitt, A M; Kleerekoper, M

1991-01-01

We present what we believe is the first case of rickets following prolonged treatment with aluminum containing antacids that bind phosphate, in an 18-year-old mentally retarded boy with cerebral palsy and spastic quadriplegia. As expected, serum calcitriol was increased and urinary phosphate excretion was very low. However, in contrast to all published cases of antacid induced hypophosphatemic osteomalacia in adults, despite a substantial increase in bone resorption reflected by urinary total hydroxyproline excretion, urinary calcium excretion was low rather than high, and significant hypocalcemia occurred after antacids were ceased and a phosphate salt administered. We suggest that the skeleton was so under-mineralized because of growth during prolonged phosphate deficiency, possibly augmented by anticonvulsant administration and immobilization, that increased bone resorption did not release enough calcium to cause hypercalciuria, or to prevent hypocalcemia during resumption of normal mineralization.

THE METABOLISM OF SILICON IN THE RAT AND ITS RELATION TO THE FORMATION OF ARTIFICIAL SILICEOUS CALCULI

PubMed Central

Keeler, Richard F.; Lovelace, Stuart A.

1959-01-01

The urinary excretion of silicon in the rat was found to be enhanced beyond normal levels by the administration of various chemical forms of silicon. The excretion was enhanced to a much greater degree by the administration of ethyl silicate than by magnesium trisilicate, sodium metasilicate, or water glass. The tolerance level of rats to sustained daily doses of ethyl silicate fed via stomach tube was approximately 15 to 30 mg. of silicon per rat per day. Urinary silicon excretion was found to be a straight line function of the concentration of ethyl silicate administered, via stomach tube, with approximately 18 per cent of the administered silicon appearing in the urine at all levels tested. Using sustained dietary additions of ethyl silicate as a means of enhancing urine silicon levels, artificial siliceous urinary calculi were consistently produced on zinc pellets implanted in the bladders of rats. PMID:13654631

Quantitation of plasma thiamine, related metabolites and plasma protein oxidative damage markers in children with autism spectrum disorder and healthy controls.

PubMed

Anwar, Attia; Marini, Marina; Abruzzo, Provvidenza Maria; Bolotta, Alessandra; Ghezzo, Alessandro; Visconti, Paola; Thornalley, Paul J; Rabbani, Naila

2016-11-01

To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage. 27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined. Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower-upper quartile]): autistic children - 6.60 nM (4.48-8.91) and 7.00 nM (5.51-8.55), and healthy controls - 6.82 nM (4.47-7.02) and 6.82 nM (5.84-8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81-8.52) versus 9.00 nM (8.41-10.71), p < .01. Urinary excretion of thiamine and fractional renal clearance of thiamine did not change between the groups. No correlation was observed between clinical markers and the plasma and urine thiamine concentration. Plasma protein dityrosine content was increased 88% in ASD. Other oxidative markers were unchanged. Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased. The latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation. Increased plasma protein dityrosine may reflect increased dual oxidase activity in response to change in mucosal immunity and host-microbe homeostasis.

Diminished 11β-hydroxysteroid dehydrogenase type 2 activity is associated with decreased weight and weight gain across the first year of life.

PubMed

Rogers, Samantha L; Hughes, Beverly A; Jones, Christopher A; Freedman, Lauren; Smart, Katherine; Taylor, Norman; Stewart, Paul M; Shackleton, Cedric H L; Krone, Nils P; Blissett, Jacqueline; Tomlinson, Jeremy W

2014-05-01

Low birth weight is associated with adverse metabolic outcome in adulthood. Exposure to glucocorticoid (GC) excess in utero is associated with decreased birth weight, but the prospective longitudinal relationship between GC metabolism and growth has not been examined. We have hypothesized that changes in GC metabolism leading to increased availability may impair growth. This was a prospective, longitudinal study with clinical measurements and 24-hour urinary steroid metabolite analysis at 1, 4, 12, 26, and 52 weeks after delivery in mothers and their babies. The study was conducted with observations and samples collected in the volunteers' own homes. Healthy mothers and newborn babies/infants participated in the study. There were no interventions. Urinary steroid metabolite excretion quantified by gas chromatography/mass spectroscopy across the first year of life in relation to change in weight was measured. The total production of the GC metabolites quantified increased across the first year of life. Markers of 11β-hydroxysteroid dehydrogenase type 1 activity increased from the age of 3 months as did those of 5α-reductase activity. After correcting for confounding variables, low markers of 11β-hydroxysteroid dehydrogenase type 2 activity was associated with reduced absolute weight and decreased weight gain over the first year of life. In the mothers, 5α-reductase activity was low at birth and progressively increased to normal over the first 6 months postpartum. Increased GC exposure as a consequence of reduced 11β-hydroxysteroid dehydrogenase type 2 activity is likely to be a critical determinant of growth in early life. This not only highlights the central role of GCs and their metabolism, but also emphasizes the need for detailed longitudinal analyses.

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

PubMed

Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

2017-01-17

Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p <2 × 10 -6 ) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10 -7 . We observed a strong association (p < 8 × 10 -8 ) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10 -6 , MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

Assessment of Dietary Sodium and Potassium in Canadians Using 24-Hour Urinary Collection.

PubMed

Mente, Andrew; Dagenais, Gilles; Wielgosz, Andreas; Lear, Scott A; McQueen, Matthew J; Zeidler, Johannes; Fu, Lily; DeJesus, Jane; Rangarajan, Sumathy; Bourlaud, Anne-Sophie; De Bluts, Anne Leblanc; Corber, Erica; de Jong, Veronica; Boomgaardt, Jacob; Shane, Alexandra; Jiang, Ying; de Groh, Margaret; O'Donnell, Martin J; Yusuf, Salim; Teo, Koon

2016-03-01

Although salt intake derived from data on urinary sodium excretion in free-living populations has been used in public policy, a population study on urinary sodium excretion has not been done in Canada. We assessed dietary sodium and potassium intake using a 24-hour urine collection in a large survey of urban and rural communities from 4 Canadian cities and determined the association of these electrolytes with blood pressure (BP). One thousand seven hundred consecutive individuals, aged 37-72 years, attending their annual follow-up visits of the ongoing Prospective and Urban Rural Epidemiology (PURE) study in Vancouver, Hamilton, Ottawa, and Quebec City, Canada, collected a 24-hour urine sample using standardized procedures. Mean sodium excretion was 3325 mg/d and mean potassium excretion was 2935 mg/d. Sodium excretion ranged from 3093 mg/d in Vancouver to 3642 mg/d in Quebec City, after adjusting for covariates. Potassium excretion ranged from 2844 mg/d in Ottawa to 3082 mg/d in Quebec City. Both electrolytes were higher in men than in women and in rural populations than in urban settings (P < 0.001 for all). Sodium excretion was between 3000 and 6000 mg/d in 48.3% of the participants, < 3000 mg/d in 46.7%, and > 6000 mg/d in only 5%. No significant association between sodium or potassium excretion and BP was found. Sodium consumption in these Canadians is within a range comparable to other Western countries, and intake in most individuals is < 6000 mg/d, with only 5% at higher levels. Within this range, sodium or potassium levels were not associated with BP. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK₁.

PubMed

Matsumoto, Takuya; Ishizaki, Yui; Mochizuki, Keika; Aoyagi, Mitsuru; Mitoma, Yoshiharu; Ishizaki, Shoichiro; Nagashima, Yuji

2017-07-17

This study examined the urinary excretion of tetrodotoxin (TTX) modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK₁. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA), l-carnitine, and cimetidine, slightly reduced by p -aminohippuric acid (PAH), and unaffected by 1-methyl-4-phenylpyridinium (MPP+), oxaliplatin, and cefalexin. Renal reabsorption was significantly reduced by PAH, but was unaffected by probenecid, TEA and l-carnitine. These findings indicate that TTX is primarily excreted by organic cation transporters (OCTs) and organic cation/carnitine transporters (OCTNs), partially transported by organic anion transporters (OATs) and multidrug resistance-associated proteins (MRPs), and negligibly transported by multidrug and toxic compound extrusion transporters (MATEs).

Effect of Docosahexaenoic Acid Ingestion on Temporal Change in Urinary Excretion of Mercapturic Acid in ODS Rats.

PubMed

Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

2007-11-01

We hypothesized a suppressive mechanism for docosahexaenoic acid (22:6n-3; DHA)-induced tissue lipid peroxidation in which the degradation products, especially aldehydic compounds, are conjugated with glutathione through catalysis by glutathione S-transferases, and then excreted into urine as mercapturic acids. In the present study, ascorbic acid-requiring ODS rats were fed a diet containing DHA (3.6% of total energy) for 31 days. Lipid peroxides including degradation products and their scavengers in the liver and kidney were determined, and the temporal change in the urinary excretion of mercapturic acids was also measured. The activity of aldehyde dehydrogenase, which catalyzes the oxidation and detoxification of aldehydes, tended to be higher in the liver of DHA-fed rats. The levels of lipid peroxides as measured by thiobarbituric acid-reactive substances and aldehydic compounds were higher and that of alpha-tocopherol was lower in the liver, and the pattern of temporal changes in the urinary excretion of mercapturic acids was also different between the n-6 linoleic acid and DHA-fed rats. Accordingly, we presume from these results that after dietary DHA-induced lipid peroxidation, a proportion of the lipid peroxidation-derived aldehydic degradation products is excreted into urine as mercapturic acids.

Effect of Docosahexaenoic Acid Ingestion on Temporal Change in Urinary Excretion of Mercapturic Acid in ODS Rats

PubMed Central

Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

2007-01-01

We hypothesized a suppressive mechanism for docosahexaenoic acid (22:6n-3; DHA)-induced tissue lipid peroxidation in which the degradation products, especially aldehydic compounds, are conjugated with glutathione through catalysis by glutathione S-transferases, and then excreted into urine as mercapturic acids. In the present study, ascorbic acid-requiring ODS rats were fed a diet containing DHA (3.6% of total energy) for 31 days. Lipid peroxides including degradation products and their scavengers in the liver and kidney were determined, and the temporal change in the urinary excretion of mercapturic acids was also measured. The activity of aldehyde dehydrogenase, which catalyzes the oxidation and detoxification of aldehydes, tended to be higher in the liver of DHA-fed rats. The levels of lipid peroxides as measured by thiobarbituric acid-reactive substances and aldehydic compounds were higher and that of α-tocopherol was lower in the liver, and the pattern of temporal changes in the urinary excretion of mercapturic acids was also different between the n-6 linoleic acid and DHA-fed rats. Accordingly, we presume from these results that after dietary DHA-induced lipid peroxidation, a proportion of the lipid peroxidation-derived aldehydic degradation products is excreted into urine as mercapturic acids. PMID:18299714

Excretion and measurement of corticosterone and testosterone metabolites in bank voles (Myodes glareolus).

PubMed

Sipari, Saana; Ylönen, Hannu; Palme, Rupert

2017-03-01

The bank vole is a commonly used model species in behavioral and ecophysiological studies. Thus, presenting a validated method for noninvasive monitoring of corticosterone and testosterone secretion is of high relevance. Here, we evaluated the effect of time of day and an ACTH challenge test on measured fecal corticosterone (FCM) and testosterone (FTM) metabolites in both sexes. Furthermore, we performed radiometabolism experiments for both steroids and sexes to study metabolism and excretion of 3 H-corticosterone and 3 H-testosterone. FCM and FTM were analysed with a 5α-pregnane-3β,11β,21-triol-20-one enzyme immunoassay (EIA) and a testosterone (measuring 17β-hydroxyandrostanes) EIA, respectively. Males had significantly higher FCM levels than females and their main excretion route was via the feces (∼72%), whereas females excreted nearly equal portions in both feces and urine. For testosterone the main excretion route was via the feces in both sexes (∼80%). The time course of excretion was similar in both sexes, but for the first time a significant difference between injected steroids was found: Corticosterone was excreted faster than testosterone, both in urine (median of peak levels: 4h vs 6h) and feces (6h vs 8h). Several metabolites were present in the feces and the tested EIAs reacted with some of them. Time of day had a significant effect on measured fecal steroid metabolites. As expected, males had significantly higher FTM levels than females. ACTH administration significantly increased FCM values; peaks were observed 4-8h after injection. In conclusion, both tested EIAs proved suited for a noninvasive measurement of glucocorticoids and androgens in bank voles. Copyright © 2016 Elsevier Inc. All rights reserved.

[Diagnostic value of radom spot albuminuria to creatinine ratio in women with preeclampsia].

PubMed

Gao, Yun-fei; Huang, Qi-tao; Zhong, Mei; Wang, Yan; Wang, Wei; Wang, Zhi-jian; Leng, Ling-zhi; Yu, Yan-hong

2012-03-01

To investigate the correlation between spot albuminuria to creatinine ratio (ACR) and 24 h urinary protein excretion in women with preeclampsia and determine the optimal cut-off values of spot ACR in mild preeclampsia and severe preeclampsia. Twenty-eight women with mild preeclampsia and 22 with severe preeclampsia at Nanfang Hospital, Southern Medical University between October 2010 and June 2011 were recruited. Maternal serum cystatin, uric acid, urea nitrogen, creatinine and albumin levels were collected and analyzed. Twenty-four hours urinary protein excretion was measured with immunoturbidimetric assay and ACR with automatic analyzer DCA2000. The correlation between ACR and 24 hours urinary protein excretion was explored. And the optimal cut-off values of the spot ACR for mild and severe preeclampsia were determined with receiver operating characteristic curve. (1) Maternal serum biochemical parameters: uric acid levels in mild and severe preeclampsia were (359 ± 114) µmol/L and (450 ± 132) µmol/L, while cystatin levels were (1.3 ± 0.3) mg/L and (1.6 ± 0.5) mg/L respectively. The differences were statistically significant (P < 0.05). Serum urea nitrogen, creatinine and albumin in mild preeclampsia were (3.6 ± 1.6) mmol/L, (52 ± 38) µmol/L and (33 ± 3) g/L, while in severe preeclampsia were (6.2 ± 3.1) mmol/L, (78 ± 59) µmol/L and (29 ± 6) g/L respectively. There were no statistical significant differences (P > 0.05). (2) Twenty-four hours urinary protein excretion and ACR: 24 hours urinary protein levels in mild and severe preeclampsia was (700 ± 160) mg and (4800 ± 2200) mg (P < 0.05). ACR in mild and severe preeclampsia was (72.7 ± 12.4) mg/mmol and (401 ± 245) mg/mmol respectively (P < 0.05). (3) There was a strong correlation between the spot ACR and 24 hours urine protein excretion (r = 0.938; P < 0.05). (4) The optimal spot ACR cut-off point for the diagnosis of preeclampsia: the optimal spot ACR cut-off point was 22.8 mg/mmol for 300 mg/24 hours of protein excretion in mild preeclampsia, the area under curve was 0.956, with a sensitivity, specificity of 82.4%, 99.4% respectively. And the optimal spot ACR cut-off point was 155.6 mol for 2000 mg/24 hours of protein excretion in severe preeclampsia, the area under curve was 0.956, with a sensitivity, specificity of 88.6%, 91.3% respectively. Compared with 24 hours urinary protein excretion, the spot ACR may be a simple, convenient and accurate indicator of early diagnosis of preeclampsia. Spot ACR may be used as a replacement for 24 hours urine protein excretion in assessment of preeclampsia. The optimal spot ACR cut off points were 22.8 mg/mmol for mild preeclampsia and 155.6 mg/mmol for severe preeclampsia.