Human Excretion Research Articles

Human urinary epidermal growth factor excretion: age, sex, and race dependence.

We measured the urinary excretion of immunoreactive epidermal growth factor (IR-EGF) in random urine specimens obtained from 358 ambulatory patients and normal subjects, aged 18-90 yr, with a homologous EGF RIA. We also measured IR-EGF excretion in 24-h urine collections from 40 additional normal subjects, aged either 20-29 or 60-69 yr, to detect possible artifacts introduced in the analysis of random urine specimens by the age-related decline in the glomerular filtration rate. Urinary IR-EGF excretion decreased in a linear fashion with increasing age. Women excreted more IR-EGF than men, and whites excreted more IR-EGF than blacks of the same age and sex, but the rate of decline with increasing age was similar for all groups. These findings may provide additional insight into the role of EGF in human renal physiology.

Characteristics of the Distribution of Plasma Atrial Natriuretic Peptides in a Cross-Sectional Study of Middle-Aged Untreated Male Workers

The distribution of the plasma levels of atrial natriuretic peptide (ANP) and their statistical correlates were studied in a random sample of 306 untreated male workers in southern Italy. Plasma ANP was not normally distributed in the population sample, with values skewed to the right and significantly shifted from the normal Gaussian curve (p = 0.003). In a multivariate analysis, plasma ANP was independently and positively related to age (p less than 0.001), urinary sodium excretion (p less than 0.01), and inversely related to creatinine clearance (p less than 0.02).These variables explained more than 12% of the variability of plasma levels of ANP. These findings confirm, in a random sample of untreated male workers, the importance of age and renal function in predicting ANP levels in the plasma and emphasize the potential importance of ANP in the control of sodium excretion in humans under free living conditions.

Environmental mutagens—Detection, and modulation of their activities

The use of blue cotton for detecting polycyclic aromatic mutagens in environmental samples (foods, human excretions, river water,etc) is reviewed. Since the invention of blue cotton has its origin in studies of mutagen modulators, these studies are also briefly reviewed.

Increased N-pentane excretion in humans: A consequence of pulmonary oxygen exposure: Morita S, Snider MT, Inada Y. Anesthesiology 64:730, 1986

Increased N-pentane excretion in humans: A consequence of pulmonary oxygen exposure: Morita S, Snider MT, Inada Y. Anesthesiology 64:730, 1986

Human urinary excretion of doxifluridine and metabolites during a 5-day chemotherapeutic schedule using fluorine-19 nuclear magnetic resonance spectrometry.

The urinary excretion of doxifluridine (5'dFUrd) and its metabolites was determined during five days of chemotherapy using fluorine-19 nuclear magnetic resonance spectrometry. The daily urinary excretion of 5'dFUrd and its metabolites was high (congruent to 100% of the 5'dFUrd administered) and nearly constant throughout the treatment. By far the major excreted compounds were unchanged 5'dFUrd and alpha-fluoro-beta-alanine which made up respectively congruent to to 40% and congruent to to 50% of the total. Neither accumulation of 5'dFUrd nor significant modifications in its metabolism were observed during the treatment.

Breath pentane analysis as an index of lipid peroxidation: a functional test of vitamin E status

Pentane, which evolves from the reaction involving omega-6 fatty acids, is a good index of lipid peroxidation. We describe a method for measuring breath pentane excretion in adult humans. After a 4-minute washout period, expired air was analyzed by gas chromatography. Breath was passed through a cooled loop of alumina to adsorb, concentrate, and release, on heating, pentane. Pentane was analyzed by a Porasil-D column with a derived calibration curve. The mean excretion of pentane in 10 normal adults was 6.34 +/- 0.96 pmol X kg-1 X min-1 (mean +/- SEM) and was significantly higher in five patients with plasma vitamin E deficiency (15.39 +/- 1.84 pmol X kg-1 X min-1). There was a significant negative correlation between pentane output and plasma vitamin E levels (r = -0.66, p less than 0.01). Moreover, breath pentane excretion was significantly decreased after a 10-d supplementation with vitamin E in five normal subjects. We conclude that breath pentane output is a sensitive, noninvasive, functional test for assessing vitamin E status.

Effect of Dietary Fibre on Urinary Thiamin Excretion in Humans

Effect of Dietary Fibre on Urinary Thiamin Excretion in Humans

Fecal excretion of intestinal glycosphingolipids by newborns and young children

Glycosphingolipids were shown to persist in human fecal excretions from birth up 2 years of age. The pattern of glycosphingolipids was dependent on blood group and secretor status of the child and changed dramatically during the first months of life. Perinatally cerebroside, hematoside and blood group active fucolipids were dominating among fecal glycolipids. From the time of weaning lactosylceramide abruptly became and then persisted as a dominating glycolipid although cerebroside, complex gangliosides and blood group active fucolipids could still be detected in feces even at 2 years of age.

Effect of diet on plasma carnitine levels and urinary carnitine excretion in humans

This investigation determines the effect of two isocaloric diet regimens on plasma carnitine and urinary carnitine excretion in man. Seven healthy men were served a high-carbohydrate, low-fat (C) or a low-carbohydrate, high-fat (F) diet for 2 wk, ie, one diet regimen for 4 d followed by a 3-d break and concluded with 4 d more on the other diet regimen. The two regimens contained the same amount of carnitine-rich food. Plasma free carnitine rose significantly from the initial value on F diet and was significantly higher from day 3 than C diet. Plasma acyl carnitine increased on both diets. Urinary excretion of carnitine increased only on F diet. Renal clearance of both free and acyl carnitine was significantly greater on F diet than on C diet. Results showed that composition of a diet with constant carnitine content influenced carnitine metabolism in man.

Increased N-Pentane Excretion in Humans

Lipid peroxidation by free radicals has been suggested as a mechanism of a lung injury caused by breathing higher than normal concentrations of oxygen. The appearance of hydrocarbons such as n-pentane in the expired gas of mammals has been proposed as in vivo evidence of lipid peroxidation. The excretion of n-pentane was studied in 15 healthy volunteers in whom excretion of exogenous n-pentane was determined over a 60- to 90-min period while breathing hydrocarbon-free gases. N-pentane elimination rates (mean +/- SEM) in the expired gas at 0, 30, 60, 90, and 120 min were 10.2 +/- 1.5, 1.6 +/- 0.2, 1.2 +/- 0.9, 1.3 +/- 0.4, and 1.3 +/- 0.3 (pmol X kg-1 X min-1), respectively. Using a specially assembled circuit, a 2-h oxygen exposure study was performed on six healthy volunteers, in whom basal n-pentane excretion varied ten-fold among individuals, from 0.25 to 2.25 pmol X kg-1 X min-1. After breathing 100% oxygen, n-pentane excretion was augmented 62-420% within 30 to 120 min. The authors conclude that lipid peroxidation may occur in humans within 30 min of breathing 100% oxygen.

Influence of ascorbic acid dose on N-nitrosoproline formation in humans.

A relationship between ascorbic acid intake and N-nitrosoproline (NPRO) excretion in humans on a controlled diet was established. Seven healthy males were placed on a low nitrate, low ascorbic acid diet for 12 consecutive days. On days 3-12, a 5.24 mmol oral dose of sodium nitrate was administered in mid-afternoon, at least 2 h after the subject's last meal. On days 4-12, a 4.35 mmol oral dose of L-proline was administered 30 min after the nitrate dose. Ascorbic acid was given in amounts which increased daily from day 5 to day 10 (0.01-5.68 mmol; 1.76-1000 mg) with the proline. Total 24 h urines were assayed for nitrate, NPRO and total ascorbic acid. Nitrate balance was monitored using [15N]nitrate. Average endogenous nitrate synthesis was 1.28 +/- 0.43 mmol/day/person. NPRO excretion was reduced by 6 nmol/day when 0.05 mmol of ascorbic acid was administered. However, as much as 5.68 mmol ascorbic acid did not return NPRO excretion to levels observed before the nitrate and proline were administered. More than 10 times the ascorbic acid required to completely inhibit NPRO formation in vitro did not return NPRO excretion to baseline levels. These data indicate that endogenous nitrosation may be more facile than predicted by the in vitro chemistry.

Effect of human insulin administration on urinary acidification in patients with insulin-dependent diabetes

1. 1. A previous study has shown that oral glucose administration results in a transient fall in urinary acid excretion in humans. The present study was undertaken to determine the effect of physiologic doses of insulin on urinary acidification while maintaining serum glucose concentration constant. 2. 2. This was accomplished by using a euglycemic insulin clamp method. Eight patients with insulin-dependent diabetes and no clinical or laboratory evidence of detectable renal disease were studied. 3. 3. Data obtained during two 2-hour periods of steady state insulin infusion rates of 0.2 and 0.5 mU/kg/min were compared. This resulted in steady state serum free insulin levels of 15 ± 0.1 and 39 ± 0.6 uU/ml respectively. 4. 4. Urinary pH and bicarbonate excretion rate rose while the excretion rates of titratable acid, ammonium and net acid fell significantly with increased insulin administration. 5. 5. These changes occurred in the absence of any significant changes in serum glucose, potassium, Ca 2+ or phosphorus concentrations or urinary excretion rates of Na +, K +, phosphorus or Ca 2+. 6. 6. These data suggest that increased insulin levels within the physiological range can result in a transient fall in the rate of urinary acid excretion. 7. 7. These findings confirm previous observations in animals and suggest that insulin may be the cause of post prandial urinary “alkaline tide”.

Increased N-pentane excretion in humans: a consequence of pulmonary oxygen exposure.

Lipid peroxidation by free radicals has been suggested as a mechanism of a lung injury caused by breathing higher than normal concentrations of oxygen. The appearance of hydrocarbons such as n-pentane in the expired gas of mammals has been proposed as in vivo evidence of lipid peroxidation. The excretion of n-pentane was studied in 15 healthy volunteers in whom excretion of exogenous n-pentane was determined over a 60- to 90-min period while breathing hydrocarbon-free gases. N-pentane elimination rates (mean +/- SEM) in the expired gas at 0, 30, 60, 90, and 120 min were 10.2 +/- 1.5, 1.6 +/- 0.2, 1.2 +/- 0.9, 1.3 +/- 0.4, and 1.3 +/- 0.3 (pmol X kg-1 X min-1), respectively. Using a specially assembled circuit, a 2-h oxygen exposure study was performed on six healthy volunteers, in whom basal n-pentane excretion varied ten-fold among individuals, from 0.25 to 2.25 pmol X kg-1 X min-1. After breathing 100% oxygen, n-pentane excretion was augmented 62-420% within 30 to 120 min. The authors conclude that lipid peroxidation may occur in humans within 30 min of breathing 100% oxygen.

Study of diurnal variations of plasma concentrations and human urinary excretion of rubidium

Daily changes in plasma levels and in urinary excretion of rubidium in man were compared with variations of other elements, particularly potassium. Plasma rubidium levels showed a daily cycle similar to potassium, and the urinary excretion of the two elements was 60–70% higher in the daytime. Among the other elements tested, daily plasma variations were observed only with Na, Zn, and Fe.

Pilot survey of urinary porphyrins from persons transiently exposed to a PCB transformer fire.

In rats and humans chronically exposed to large amounts of PCB (polychlorinated biphenyls) and PCDF (polychlorinated dibenzofurans), the urinary excretion of uroporphyrin and coproporphyrin are altered. However, porphyrin excretion in humans after acute transient low level exposure has not been evaluated. Following such an exposure in which bystanders and firefighters were in contact with smoke from a PCB transformer fire, we surveyed 90 self-referred individuals by questionnaire and by determining single 24 hour urinary excretion of uroporphyrin and coproporphyrin 2-4 weeks after the fire. Questionnaire variables that assessed exposure were not associated with the magnitude of either uroporphyrin or coproporphyrin excretion. Uroporphyrin excretion was slightly elevated in nine subjects (range 66-106 micrograms/24 hours, normal less than 60), which is much less than in clinical cases of porphyria cutanea tarda. Uroporphyrin excretion was inversely correlated with coproporphyrin excretion (r = -0.3844, p = 0.0002). For 5 subjects (3 with elevated initial uroporphyrin excretion) retested at 3-4 weeks after the fire, all 5 showed increases in uroporphyrin and decreases in coproporphyrin excretion when compared to initial determinations. These two reciprocal relationships would be the expected result from inhibition of uroporphyrinogen decarboxylase, a known experimental effect of PCB and PCDF in mice. Overall, urinary porphyrin excretions were not altered or sensitive measures of exposure.

Radioimmunoassay for etoposide and teniposide

A radioimmunoassay for VP-16 or VM-26 was developed by using tritiated ligand and antisera produced from rabbits immunized with succinyl-VP-16 bovine serum albumin conjugates. Separate determinations of VP-16 and its hydroxy acid, a metabolite which cross-reacted with the VP-16 antisera, could be accomplished by extracting samples with chloroform in which the metabolite was insoluble. The assay was reproducible and sensitive. Extracted standard curves were linear from 0.025 to 5 μg for VP-16 and 0.1 to 10 μg for the hydroxy acid per 0.5 ml assay mixture. Fifty percent inhibition of binding was achieved at 0.066 and 0.55 μg for VP-16 or VM-26 and the metabolite, respectively. Preliminary disposition studies in mice and dog, and human urinary excretion support the application of the assay in pharmacologic studies.

Epidermal growth factor in human urine from birth to puberty.

The highest concentrations of epidermal growth factor (EGF) are found in urine, but the physiological role of urinary EGF is unknown. We studied human urinary EGF excretion, by measuring its concentration with a specific homologous RIA, in 265 healthy children from birth until age 16 yr. The absolute concentrations varied widely between individuals. Mean values were approximately 10 ng/ml in 1- to 30-day-old infants; 2.5-fold higher values were found in infants aged 2 to 12 months. During the second year there was a further rise to about 70 ng/ml, and urinary EGF excretion was in the same range in older subjects. The EGF/creatinine concentration ratio was less variable. The mean ratio increased 6-fold from birth to the second year of life. Thereafter, the EGF/creatinine ratio decreased gradually to one-third of the peak level at puberty. No sex difference was found.

The correlation between human plasma melatonin levels and urinary 6-hydroxymelatonin excretion

A significant correlation (0.76) has been found between nighttime peak plasma melatonin levels and the 24-h urinary excretion totals for conjugated 6-hydroxy-melatonin for a group of 22 women. This study validates the comparison of plasma levels of the hormone or urinary levels of its metabolite to assess pineal gland production of melatonin in humans.

Identification and quantification of urinary metabolites of dinitrotoluenes in occupationally exposed humans

Rats exposed to technical grade dinitrotoluene (DNT) develop hepatocellular carcinomas. Humans may be expsed to DNT during its manufacture and use. To permit comparisons of human excretion patterns of DNT metabolites with those previously observed in rats, urine specimens were collected over a 72-hr period from workers at a DNT manufacturing plant. Samples were analyzed for 2,4- and 2,6-DNT and putative metabolites by gas chromatography-mass spectrometry. Urine from workers exposed to DNT contained 2,4- and 2,6-DNT, 2,4- and 2,6-dinitrobenzoic acid, 2,4- and 2,6-dinitrobenzyl glucuronide, 2-amino-4-nitrobenzoic acid, and 2-( N-acetyl)amino-4-nitrobenzoic acid. Excretion of these metabolites peaked near the end of the workshift, but declined to either very low or undetectable concentrations by the start of work the following day. The calculated half-times for elimination of total DNT-related material detected in urine ranged from 1.0 to 2.7 hr, and those of individual metabolites from 0.8 to 4.5 hr. The most abundant metabolites were 2,4-dinitrobenzoic acid and 2-amino-4-nitrobenzoic acid, collectively accounting for 74 to 86% of the DNT metabolites detected. The data indicate that urinary metabolites of DNT in humans are qualitatively similar to those found in rats, but quantitative differences exist in the relative amounts of each metabolite excreted.

Correlation between bioassay and radioimmunoassay for erythropoietin in human serum and urine concentrates.

Both immunoreactive erythropoietin (Ep) and biologically active Ep were measured in 23 samples of human serum and 21 concentrates of human urine. Immunoreactive Ep was measured by radioimmunoassay (RIA). Biological activity was determined in the plethoric mouse bioassay in which 59Fe incorporation was converted to units of Ep from standard reference curves. Low values for Ep were determined from standard curves plotted as probits to improve sensitivity for levels of Ep as low as 30 mU/ml. Ep levels in 35 samples ranged between 30 and 1000 mU/ml by both assays; in 9 samples Ep was 15.2-37.5 mU/ml by RIA but was not detectable by bioassay. Analysis of the data for the 35 samples in which Ep could be measured by both assays showed a strong correlation between the values obtained by the two assays. These results indicate that the RIA used in these experiments detects biologically active Ep in human serum and urine when it is present in amounts only moderately higher than normal. The ultrafiltration method used for preparation of urine samples was effective in concentrating Ep in some urines, but the results were too erratic and nonquantitative to permit its use as a method for quantifying human urinary Ep excretion.