Daily Excretion Rates Research Articles

Increased spillover of dopa into arterial blood during dietary salt loading

1. We measured urinary excretion rates of dopamine (3,4-dihydroxyphenethylamine) and dopa (3,4-dihydroxyphenylalanine) and the spillover rate of dopa into arterial blood during dietary salt loading in conscious Dahl salt-sensitive and salt-resistant rats with intact or denervated kidneys. 2. Dopa spillover was calculated from the steady-state clearance of intravenously infused L-[3H]dopa and arterial levels of endogenous dopa. 3. Daily excretion rates of dopa and dopamine increased by about sixfold during salt loading in both rat strains. Bilateral renal denervation delayed these increases and the natriuretic responses. 4. During dietary salt loading, dopa spillover increased to approximately the same extent as simultaneously measured dopamine excretion. 5. The results suggest that increases in urinary excretion of dopamine during dietary salt loading can be accounted for by increases in the release of dopa into the bloodstream and that the renal nerves contribute to the dopa and dopamine excretory responses.

Phenylacetylglutamine and Hippuric Acid in Uremic and Healthy Subjects

Phenylacetyglutamine (PAG) and hippuric acid (HA) were determined in protein-free filtrates of plasma and urine from patients with chronic renal failure and healthy subjects, using reverse phase high performance liquid chromatography. Plasma accumulation of the metabolites was detected when the creatinine clearance was below 15 ml/min. Protein-binding studies showed that PAG was not bound to plasma proteins but that HA was partly bound. Concentrations of PAG and free HA in plasma did not correlate with values of serum urea or creatinine. Hemodialysis decreased the plasma concentration of PAG and free HA to about the same extent as that of urea and creatinine. The average renal clearances of PAG and HA were about 1.4 and 5 times higher, respectively, than the creatinine clearance. The daily excretion rates of PAG, HA, urea, and creatinine were similar in non-dialysis patients with a creatinine clearance higher than 15 ml/min and in healthy subjects, whereas patients with a creatinine clearance below 15 ml/min had lower excretion rates of urea, creatinine, and HA. However, the average excretion rate of PAG was in the same range in uremic and healthy subjects. The excretion rate of HA, but not of PAG, correlated with that of urea and creatinine.

Disposition and excretion of 2,3,4,7,8-pentachlorodibenzofuran in the rat

The disposition of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), a highly toxic environmental contaminant which accumulates in human tissues, was examined in the male Fischer rat after iv and oral exposure. Greater than 70% of an oral dose of 0.1, 0.5, or 1.0 μmol PeCDF/kg body wt was absorbed by the gastrointestinal system. After either oral or iv administration of 0.1 μmol/kg, the dibenzofuran was rapidly removed from the blood and accumulated in the liver and adipose tissue and to a lesser extent in the skin and muscle. Three days after administration, 70% of the iv dose of PeCDF was found in the liver, 7% in the fat, 1% in the skin, and 0.5% in the muscle. Route of exposure had little effect on tissue distribution. TLC analyses indicated that >;99% of the [ 14C]-PeCDF-derived radioactivity which had accumulated in the liver and adipose tissue was unmetabolized PeCDF which was eliminated very slowly ( t 1 2 = 193 and 69 days , respectively). The whole body half-life calculated from the daily fecal excretion rate was ∼64 days. Excretion occurred primarily via the feces. No radioactivity was detected in expired air and <0.02% was detected in the urine. TLC analysis of fecal extracts indicated >90% of the [ 14C]PeCDF-derived radioactivity in the feces was polar metabolites of the parent compound. Pretreatment with 500 μg PeCDF/kg body wt caused biliary excretion to nearly double. Treatment of bile with β-glucuronidase or arylsulfatase had little effect on the chromatographic profile. Therefore, PeCDF was readily absorbed from the gastrointestinal tract, concentrated primarily in the liver, and was slowly eliminated from the body as polar metabolites. The long half-life and high body burden of PeCDF suggest that the toxicity of this chemical may be enhanced due to bioaccumulation upon chronic low-level exposure.

Interrelationships between dietary carbohydrates, B cell function and rate of ketogenesis during underfeeding in obese patients.

Six matched groups of obese patients underwent 3-week selective hypocaloric regimens which consisted of a 240 or 480 kcal/day liquid formula diets for groups 1-4 and an 800 kcal/day conventional diet for groups 5 and 6. Carbohydrate intake ranged from 19 to 112 g/day so that for each energy level two different amounts of carbohydrates were administered. Body weight loss was similar in groups 1-4 and significantly lower in groups 5 and 6. During treatment fasting serum insulin (but not serum C-peptide) levels and the daily urine excretion rate of C-peptide showed quite a similar fall in all groups. Fasting glucagon levels did not change. The rate of ketogenesis which developed during each nutritional treatment was inversely related to the amount of dietary carbohydrates; moreover, a significant correlation was found between percent variation of ketoacids and those of fasting IRI (r = -0.42; p less than 0.01) and glucose (r = -0.52; p less than 0.01) concentrations, but not with those of fasting C-peptide and its daily urine excretion rate. In conclusion, it seems that during underfeeding (1) low- and high-carbohydrate-containing regimens are substantially equipotent stimuli secretagogues of insulin secretion, and (2) carbohydrate (or glucose) availability affects ketogenesis even through noninsulin-mediated mechanisms.

Abnormal diurnal changes in in-vivo platelet activation in patients with atherosclerotic diseases

We measured the urinary excretion of beta-thromboglobulin in timed urine samples collected by 2 groups of healthy volunteers, (group I, n = 20, mean age 34 years, group II, n = 15, mean age 64 years) and by patients (n = 40) with symptomatic atherosclerotic diseases. Older healthy subjects were found to excrete high amounts of BTG in comparison to young subjects (302.25 ± 50.61 vs 219.65 ± 59.31 ng/day, P < 0.05). Higher ( P < 0.01) levels of urinary BTG were observed in patients with coronary (427.61 ± 179.96 ng/day), cerebral (422.13 ± 223.2 ng/day) and peripheral (454.16 ± 269.05 ng/day) arterial diseases and in diabetic patients with diffuse vascular complications (613.71 ± 253.07 ng/day). The diurnal variability of BTG excretion, measured as coefficient of variation (C.V. %) of the mean daily excretion rate, was higher ( P < 0.001) in atherosclerotic patients (70.59 ± 26.57) as compared with the similar values observed in the control groups of young (32.05 ± 14.54) and older subjects (26.38 ± 8.4). Comparable diurnal variabilities of the creatinine excretion rate were observed in the control groups and in patients. These data indicated that in vivo platelet activation may occur in atherosclerotic patients with a distinctive high fluctuation rate.

Radioimmunoassays for type III procollagen amino-terminal peptides in humans.

Use of radioimmunoassay for the amino-terminal propeptide of type III procollagen for monitoring fibrotic processes in humans has been frustrating because of the nonparallel relation between results for the standard bovine antigen and human serum samples. In the radioimmunoassays I developed for this propeptide and its monomeric Col 1 domain, based on use of antigens from humans, serum samples generated less-steep inhibition curves than did the standard antigen in the propeptide assay; in the Col 1 assay, however, serum and urine samples both generated inhibition curves having the same slope as that generated with the standard Col 1 peptide. Concentrations of human fragment Col 1 in serum samples as measured with the Col 1 assay were usually double those obtained with the human propeptide assay, which in turn were two- to threefold those obtained with the bovine antigen assay. In control subjects and alcoholic cirrhotics the concentrations of antigen in urine and the daily excretion rates as measured with the assay for human Col 1 exceeded those reported previously. The presence of different antigen forms was demonstrated with both assays by gel-filtration analysis of serum and urine samples. The assay for human Col 1 should be suitable for routine clinical chemical use.

129 PROFILES OF STEROID EXCRETION IN THE NEONATAL PERIOD

Steroid excretion of infants with and without adrenal disease has been determined during the first weeks of life. Steroid conjugates were hydrolysed before conversion to thermostable derivatives for gas chromatographic (GC) analysis and combined GC-mass spectrometry. During the first days of life, steroid sulphates derived from the fetal adrenal zone predominate in all infants. These steroids were separated from the products of the definitive adrenal cortex which are excreted as free steroids and conjugates with glucuronic acid. Cortisol in the normal newborn is excreted as lB and 6 hydroxylated metabolites. From studies of infants with adrenal hyperplasia cortisol biosynthetic precursors are metabolised differently in the neonatal period compared with their subsequent fate. Hence 17-hydroxyprogesterone is subject to active 15B-hydroxylation while 11-deoxycortisol is 6 -hydroxylated. These hydroxylation reactions are of minor importance after the first weeks of life. In premature infants the daily excretion rates of 5-ene steroids showed low amplitude oscillatory patterns with frequency like the pattern of maternal oestrogen excretion in the last trimester. No such pattern was observed from the excretion of cortisol metabolites. Thus, steroid reactions of the fetus are retained variably in neonatal life and the fate of steroids must be considered when evaluating the function and role of the adrenal at this time of life.

Experimental studies on some trophic relationships in juvenile pike, Esox lucius L.

A postprandial increase in ammonia nitrogen excretion and oxygen consumption rates was observed in juvenile pike fed a natural diet or an artificial dry diet. Specific growth rate of natural diet fed pike (2.4%) was lower than that of pike fed the artificial diet (3.1%). Fifty per cent of ingesta was evacuated within 5–6 h in pike of 25 mg body weight and 9–10 h in those weighing 150mg. Daily nitrogen excretion rates were related to body weight. Respiratory quotient and energy retention efficiency were affected by the nature of the diet ingested by pike. Parameters of the energy balance (losses, retention, increment due to feeding) were related to energy intake.

Renal Function in Unanaesthetized River Lampreys (Lampetra Fluviatilis L.): Effects of Anaesthesia, Temperature and Environmental Salinity

ABSTRACT Improved estimates of urine flow rates of lampreys in various salinities were obtained by the collection of urine for periods of up to 48 h from minimally-stressed, unanaesthetized fish, following catheterization of the urinogenital papilla. The mean urine flow rate of freshwater lampreys was 200·7 ± 14·3 ml kg−1 day−1. Urine flow in freshwater lampreys was correlated with spontaneous changes in gill ventilation rate. MS222 anaesthesia reduced both ventilation and urine flow rates, but pronounced effects were only observed at concentrations greater than those needed to induce light anaesthesia (50–55 mgl−T). Urine flow rate in unanaesthetized fish was extremely sensitive to rapid (6°Ch−1) changes in temperature and Q10 (6–16°C) was approximately 5. Urine flow rate decreased rapidly as the osmotic difference between the body fluids and environment approached zero, and the rate of flow in 30% seawater lampreys was only 7·6% that of freshwater fish. There was no evidence for an effect of environmental calcium concentration on branchial osmotic permeability. Extensive tubular reabsorption of ions occurred in freshwater lampreys. The total daily excretion rate of sodium ions generally decreased in salinities hyperosmotic to the plasma, indicating enhanced reabsorption, but secretion of magnesium and sulphate ions was greatly increased. Urine osmolarity was significantly increased in lampreys in hyperosmotic salinities. Present data compare favourably with data obtained previously from anaesthetized animals, indicating that renal function in lampreys is not significantly impaired by light MS222 anaesthesia.

Melatonin metabolite excretion during childhood and puberty.

Daily urinary excretion of conjugated 6-hydroxymelatonin, the major metabolite of the pineal hormone melatonin, has been determined in 54 boys and 47 girls (aged 3-16 yr) and 20 normal adults to determine whether a change in melatonin production is seen during the maturation of reproductive function in humans. There was no correlation between daily excretion rates and age in children, and the excretion rates were similar to those in adults. In addition, children of all ages had normal circadian patterns of 6-hydroxymelatonin excretion from the earliest age tested. A significant increase in 6-hydroxymelatonin excretion was observed at the time of the onset of breast development (Tanner stage II) in girls. No similar difference was seen during puberty in males. The significance of this difference in Tanner II girls is not known.

The risks of asymptomatic hyperuricaemia and the use of uricosuric diuretics.

Introduction of new uricosuric diuretics will be accompanied by the unknown risk factors associated with the use of any new drug, as demonstrated by reports of hepatic toxicity associated with ticrynafen. In addition to unexpected reactions, there are potential risks related to induction of uricosuria, which are serious and have been reported to occur. More importantly, the risk of developing clinical gout or coronary heart disease due to mild asymptomatic hyperuricaemia appears minimal, so indications for the use of uricosuric diuretics are limited. If a uricosuric diuretic is thought necessary (and is available), it would seem prudent to measure the daily excretion rate of uric acid to identify those patients with hyperuricaemia related to overproduction of uric acid. A uricosuric diuretic should be avoided in those patients, as well as in patients with uric acid stones, and possibly in those with calcium stones. A uricosuric diuretic might be useful for patients with hypertension who also have hyperuricaemia due to a low excretion of uric acid.

Circadian rhythmicity of the urinary excretion of mercury, potassium and catecholamines in unconventional shift-work systems.

The round the clock urinary excretion rates of mercury were assessed for two series of unconventional patterns of activity and sleep in subjects who were not exposed to occupational, medical, or other obvious sources of mercury. In the first series the urine was collected in 3-h periods from six subjects during the first and last 2 d of a four-week, continuous 6-h shift (car ferry, watches either 0800--1400 and 2000--0200 or 1400--2000 and 0200--0800). In the second series the urine was collected in 4-h periods from five subjects working an 8-h experimental rotation shift compressed into 5 d (work two mornings--8-h interval--work two nights--8-h interval--work two afternoons). The mean daily excretion rate of the 11 subjects (48 investigation days, 334 urine samples) was 14.5 pmol of mercury/min (range 5.5--24.4 pmol of mercury/min). The mercury excretion oscillated regularly during 24 h by +/- 20--25% of the individual's daily mean excretion rates. The peak excretion rates were found at 0652 in the first and 0642 in the second series (cosinor treatment). Due to the circadian rhythm the mean 24-h excretion rates were best represented (correlation coefficient 0.92) by analyses of urine produced around noon (spot samples, collection periods 1100--1400 and 1000-1400, respectively). The circadian oscillations of mercury excretion were not influenced by the widely different and varying activity-sleep patterns of the two series. The rhythmicity of potassium excretion (peaks at around 1400) was more irregular. The stable oscillations of mercury excretion contrasted most with the excretion of adrenaline and noradrenaline, which, without losing the basic 24-h rhythmicity, closely followed the unconventional patterns of activity and sleep.

Detection of a thyroxine-binding protein physicochemically similar to serum thyroxine-binding globulin in normal human urine.

Urine samples from 10 normal adult males were analyzed for T4-binding globulin (TBG) employing a sensitive and specific RIA for serum TBG. Urine TBG was detected at a concentration of 1.74 +/- 0.87 microgram/100 ml (mean +/- SD). The excretion rate was 13.2 +/- 6.5 microgram/g creatinine. There was no correlation between the daily excretion rate of TBG and the total urinary protein (r = 0.52). Analyses of this T4-binding protein by gel filtration and on both reverse flow paper and gel electrophoresis demonstrated similar characteristics to those of serum TBG and purified TBG. The maximum T4-binding capacity of urine TBG, determined by reverse flow paper electrophoresis and equilibrium dialysis, was similar to that of serum TBG. The association constant for T4 of urinary TBG (0.46 +/- 0.20 X 10(10) M-1), determined by equilibrium dialysis, was significantly less (P less than 0.01) than that of serum TBG at 1.43 +/- 0.23 X 10(10) M-1). The Scatchard analysis of the urinary data demonstrated two T4-binding sites, one of high affinity consistent with TBG and one of low affinity consistent with albumin. It is concluded that the TBG present in urine has the major physical and biochemical features of the intact molecule, but that minor conformational and/or charge alterations occurred during renal excretion. Interpretation of data on thyroid hormones in normal urine should take the presence of TBG into consideration.

Excretory Rates in Posttransplant Cystinuric Patient

To the Editor.— While studying phenotypes of cystinuria, we measured the daily excretion rates of a 28-year-old man with a nine-year history of cystine stone formation and who, during the course of our study, received a kidney transplant at a nearby hospital because of end-stage kidney failure. Our measurements of his cystine and dibasic amino acid excretion are of interest since they are, to our knowledge, the first record of a surgical cure of the disease. The patient's genetic constitution, predicted from the phenotype expressions of his obligate carrier daughter and mother, respectively, is compound heterozygous for the types I and III of cystinuria. 1,2 A brother, furthermore, expressed the type III heterozygous phenotype. The pretransplant excretion rates are clearly abnormal (Table) but lessso than those of other stone-forming patients in our experience. We attribute the milder biochemical expression to his renal failure, a characteristic of severely affected cystinuric

Mineralocorticoid activity in patients in the early benign phase of essential hypertension

The major parameters of aldosterone metabolism (daily secretion and excretion rates, metabolic clearance rate and plasma levels) have been measured in carefully selected patients in the early benign phase of essential hypertension and in control subjects by double isotope dilution assay and, more recently, by radioimmunoassay. The results show: (1) a significant mean increase in plasma aldosterone concentration in two different groups of patients in the early benign phase of essential hypertension despite a daily secretion and excretion rate which was found normal in the great majority of patients; (2) a decreased metabolic clearance rate in 80% of all hypertensive patients studied; (3) a decrease in hepatic blood flow as measured by a constant infusion or indocyanine green. These observations are consistent with the absence or the blunting of aldosterone response to a variety of stimuli (severe sodium restriction, furosemide administration, severe hemorrhage) which increase plasma renin activity. Plasma progesterone concentrations are significantly increased in patients in the early phase of benign essential hypertension and their response to severe sodium restriction is significantly smaller than that of normal subjects. These studies indicate definite disturbances in aldosterone metabolism and regulations in the early benign phase of essential hypertension.

The metabolic clearance rate and urinary excretion of oral contraceptive drugs: II. Mestranol

Mestranol, a synthetic estrogenic drug, was administered to seven normal females and the rate of disappearance of the drug and its metabolites from the plasma was followed. In addition, urine was collected over the 5 days following injection and analyzed for daily excretion rates and for types of conjugation of mestranol metabolites. The rate of clearance of mestranol from the plasma was rapid with an average metabolic clearance rate (MCR) of 1,247 L. per day. Following these initial determinations, subjects were placed on a commercial oral contraceptive preparation containing 80 μg of mestranol per day. Each subject completed six cycles of this drug preparation; after completion, the MCR and urinary excretion rate of the drug were redetermined. Statistical comparisons of the MCR and urinary excretion rates made before and again after the six cycles of the drug show that prolonged mestranol administration had no effect on the rate of clearance (MCR), the rate of urinary excretion, or the mode of conjugation of mestranol or its metabolites.

A prolidase deficiency in man with iminopeptiduria

A deficiency in the enzyme, prolidase (EC 3.4.3.7), is described in a patient with iminopeptiduria and clinical findings that suggest a defect in collagen metabolism. The massive iminopeptiduria is unique to this disorder, with daily proline excretion rates of 1.76 g. Fifteen peptides were characterized and quantitated from a deproteinized, amino-acid-free, 24-hr urine collection using column chromatographic procedures. Amino acid analysis revealed the peptides to be di- and tri-peptides containing proline plus another amino acid, “X.” Dansylation revealed “X” to be amino-terminal in each case. Prolidase, an enzyme known to cleave X-proline bonds, was measured by two separate methods. Enzyme activity in the patient's red and white cells was absent to markedly decreased as compared to age-matched controls. Furthermore, the activity of the enzyme in the mother's and maternal grandfather's white cells was less than that found in adult controls, suggesting a heterozygous condition. The maternal grandmother's enzyme activity was normal. The enzyme data is suggestive of an autosomal recessive disorder. This patient represents the first direct demonstration of a prolidase deficiency in man.

Fecal excretion of thyroxine in warm- and cold-acclimated rats.

The daily excretion rate of fecal thyroxine was determined in warm- or cold-acclimated rats. Fecal thyroxine and dietary thyroxine were measured directly by a competitive protein binding analysis technique. An analysis of the Master laboratory chow diet confirmed that one-third of the iodine content was in the form of thyroxine. When fed this diet, cold-acclimated rats ingested 70% more thyroxine and excreted 75% more thyroxine than warm-acclimated rats. On the other hand, rats fed a thyroxine-free diet supplemented with iodine in the drinking water, while showing no significant increase in fecal excretion of thyroxine upon cold acclimation, developed a similar degree of cold resistance as those fed the Master laboratory chow containing 0.58 μg/g of thyroxine. Rats on a thyroxine-free diet showed a significantly lower fecal thyroxine excretion rate at both temperatures than did those on the Master laboratory chow. The results indicate that the greater fecal clearance of thyroxine usually found in cold-acclimated rats is not an essential feature of cold acclimation and depends either on the increased fecal bulk or the increased ingestion of dietary thyroxine.

The estimation of 3,4-dihydroxymandelic acid in urine and its excretion by man.

Abstract A method is described for the estimation of 3,4-dihydroxymandelic acid (DHMA) in human urine. It consists of the following steps: adsorption of DHMA on a column of alumina, passage of the alumina eluate through a column of cation exchange resin, extraction of DHMA into ethyl acetate, conversion of DHMA to protocatechuic aldehyde by shaking the ethyl acetate extract with aqueous ammonia, extraction of the aldehyde into ethyl acetate, evaporation of the extract, and solution of the residue in absolute methanol. Protocatechuic aldehyde is estimated by the increase of fluorescence affected by the addition of a trace of concentrated sulfuric acid. An internal standard is analyzed with every sample. The specificity of the method is high; in particular, it is free from interference from 3,4-dihydroxyphenylacetic acid. No evidence was found for the presence of an acid-hydrolyzable conjugate of DHMA in urine. The mean daily excretion rate was found to be of the order of 100 μg. Excretion rates in cases of pheochromocytoma may be about ten times as high as the normal average.

Nonhormonal iodine escape from the normal and abnormal thyroid gland.

ABSTRACT A kinetic analysis of iodine metabolism was performed on 7 normal subjects on an iodine-restricted diet, 7 normal subjects and 7 subjects with simple goiter on the usual Japanese diet. 1) The mean intrathyroidal iodine content was 12.2, 27.6 and 43.3 mg/gland, respectively. 2) The escape of nonhormonal iodine from the thyroid gland was confirmed in all cases despite the restriction of dietary iodine. 3) After the occurrence of leveling off of the daily urinary excretion of 131I, the mean daily excretion rate of urinary 131I (E*) was 5 times greater than the mean daily degradation rate of labeled hormonal iodine in the extrathyroidal organic iodine pool (D*) and was 3 times greater than the mean daily secretion rate of the labeled hormonal iodine from the gland (H*). 4) The ratio of the mean daily excretion rate of urinary 131I (E*) to the mean daily secretion rate of PB131I from the gland (H*) was used as one of the indices for the release of nonhormonal iodine. The relationship in 19 subjects be...