Human Excretion Research Articles

Olive Oils Rich in Natural Catecholic Phenols Decrease Isoprostane Excretion in Humans

This study was undertaken to evaluate, in humans, the antioxidant activity of olive oil phenolics, namely hydroxytyrosol and oleuropein aglycone that share an orthodiphenolic (catecholic) structure. Human volunteers were administered olive oil samples containing increasing amounts of an olive oil phenolic extract that was characterized by gas-chromatography/mass spectrometry. The administration of phenol-rich oils was dose-dependently associated with a decreased urinary excretion of 8-iso-PGF2α, a biomarker of oxidative stress. Also, a statistically significant negative correlation between homovanillyl alcohol (HValc, hydroxytyrosol's major metabolite, formed through the COMT system) and F2-isoprostanes excretion was found. Thus, the administration of oil samples with increasing, albeit low, concentrations of orthodiphenolic compounds, namely hydroxytyrosol and oleuropein aglycone, results in a dose-dependent reduction in the urinary excretion of 8-iso-PGF2α. The statistically significant negative correlation between 8-iso-PGF2α and HValc urinary concentrations suggests that this metabolite better reflects the in vivo activities of hydroxytyrosol.

Does Iron Concentration in a Liver Needle Biopsy Accurately Reflect Hepatic Iron Burden in β-Thalassemia?

β-Thalassemia major is an autosomal recessive disease characterized by absent or decreased synthesis of the β-globin gene (1). Thalassemic children, estimated at 100 000 worldwide, are affected by chronic anemia and need regular blood transfusion (2). Because of the limited capacity of iron excretion in humans, the iron in transfused red cells accumulates in the body. The liver, heart, and pancreas are the target organs of iron-induced injury; therefore, the major pathological manifestations observed in β-thalassemia major are chronic liver disease, evolving to cirrhosis, and dilative cardiomyopathy, both characterized by severe iron deposition (3)(4). The dangerous effects of iron excess can be managed by administration of chelators capable of removing iron from transferrin, ferritin, and other iron stores (5)(6)(7). Determination of the hepatic iron concentration (HIC) is one of the most valid procedures in assessing real body iron burden (8)(9)(10), which is important for adjusting each patient’s chelation therapy over the years. HIC usually is measured on one part of a needle biopsy core, and the measured value is considered representative of the iron concentration in the whole liver (11). In 1995, a study by our group (3) first showed that iron is unevenly distributed in the livers of β-thalassemic patients, and therefore, the iron content determined in a small liver fragment should be interpreted with caution because it cannot be considered a true representation of the mean HIC. These data were confirmed by us (12)(13)(14) and by other authors (15), who reported differences in HIC measurements on liver biopsy specimens. Recently, a striking difference in HIC was found in biopsy samples from cirrhotic livers (range, 60–2851 μg/g dry weight) (16). It therefore seemed of interest to measure iron concentrations in a large number of needle …

Interaction between the actions of taurine and angiotensin II.

The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion of taurine has been linked to developmental defects, retinal damage, immunodeficiency, impaired cellular growth and the development of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy promoting drinks. Nonetheless, the use of taurine as a drug to treat specific diseases has been limited. One disease that responds favorably to taurine therapy is congestive heart failure. In this review, we discuss three mechanisms that might underlie the beneficial effect of taurine in heart failure. First, taurine promotes natriuresis and diuresis, presumably through its osmoregulatory activity in the kidney, its modulation of atrial natriuretic factor secretion and its putative regulation of vasopressin release. However, it remains to be determined whether taurine treatment promotes salt and water excretion in humans with heart failure. Second, taurine mediates a modest positive inotropic effect by regulating [Na+]i and Na+/Ca2+ exchanger flux. Although this effect of taurine has not been examined in human tissue, it is significant that it bypasses the major calcium transport defects found in the failing human heart. Third, taurine attenuates the actions of angiotensin II on Ca2+ transport, protein synthesis and angiotensin II signaling. Through this mechanism taurine would be expected to minimize many of the adverse actions of angiotensin II, including the induction of cardiac hypertrophy, volume overload and myocardial remodeling. Since the ACE inhibitors are the mainstay in the treatment of congestive heart failure, this action of taurine is probably very important.

Sulfation of “Estrogenic” Alkylphenols and 17β-Estradiol by Human Platelet Phenol Sulfotransferases

We have investigated the ability of alkylphenols to act as substrates and/or inhibitors of phenol sulfotransferase enzymes in human platelet cytosolic fractions. Our results indicate: (i) straight chain alkylphenols do not interact with the monoamine-sulfating phenol sulfotransferase (SULT1A3); (ii) short chain 4-n-alkylphenols (C < 8) are substrates for the phenol-sulfating enzymes (SULT1A1/2), which exhibit two activity maxima against substrates with alkyl chain lengths of C1-2 and C4-5; (iii) long chain 4-n-substituted alkylphenols (C >/= 8) are poor substrates and act as inhibitors of SULT1A1/2; (iv) human platelets contain two activities, of low and high affinity, capable of sulfating 17beta-estradiol, and 4-n-nonylphenol is a partial mixed inhibitor of the low affinity form of this activity. We conclude that by acting either as substrates or inhibitors of SULT1A1/2, alkylphenols may influence the sulfation, and hence the excretion, of estrogens and other phenol sulfotransferase substrates in humans.

Over-the-counter anabolic steroids 4-androsten-3,17-dione; 4-androsten-3beta,17beta-diol; and 19-nor-4-androsten-3,17-dione: excretion studies in men.

Since the appearance of 4-androsten-3,17-dione (I) as a nutritional supplement in early 1997, we have frequently observed a characteristic deterioration of endogenous steroid profiles in athletes' urine in routine anabolic steroid testing in which concentrations of major endogenous urinary steroids and testosterone exceed normal. Human excretion studies are performed with I and newer, over-the-counter "supplements" 4-androsten-3beta,17beta-diol (II) and 19-nor-4-androsten-3,17-dione (III). Endogenous urinary steroids affected by I and II are androsterone, etiocholanolone, their hydroxylated derivatives 5alpha- and 5beta-androstan-3alpha,17beta-diols, testosterone, and epitestosterone. Their concentrations briefly increase by one to two orders of magnitude and return to normal 24 h after oral administration of I and II. The average male may test positive for testosterone because testosterone concentration rises faster than that of epitestosterone, causing the testosterone/epitestosterone (T/E) ratio to rise above the positive cutoff of 6:1. A remarkable distinction in excretion patterns was observed in eastern Asian men, for whom I and II did not affect urinary concentrations of testosterone and did not increase the T/E ratio. First-pass metabolism deactivates most of the orally administered drugs I and II, rapidly converting them into inactive androsterone and etiocholanolone. Drug II is a more effective testosterone booster because of its different metabolic pathway. After the use of III, a precursor of the potent anabolic nandrolone, high concentrations of norandrosterone and noretiocholanolone appear in urine, similar to nandrolone. These are detectable in urine for 7-10 days after a single oral dose of III (50 mg).

Occurrence and Environmental Behavior of the Chiral Pharmaceutical Drug Ibuprofen in Surface Waters and in Wastewater

Pharmaceutical compounds can reach detectable concentrations in rivers and lakes if production and use are sufficiently large and the compounds show some mobility and persistence in the aquatic environment. In this study, we report on the occurrence and on the enantiomer composition of the chiral pharmaceutical drug ibuprofen (IB) in surface waters and in samples from wastewater treatment plants (WWTPs). Enantioselective gas chroma tography and detection by mass spectrometry/mass spectrometry was used for analysis. IB was present in influents of WWTPs at concentrations of up to 3 μg/L with a high enantiomeric excess of the pharmacologically active S enantiomer (S ≫ R), as from human urinary excretion. The principal human urinary metabolites of IB, hydroxy-IB and carboxy-IB, were observed in WWTP influents at even higher concentrations. In contrast to other pharmaceutical compounds such as clofibric acid and diclofenac, IB and its metabolites are then efficiently degraded (>95%) during treatment in WWTPs. ...

Renal Transport of Urate in Humans.

The theory of the "four-component model" of urate excretion in humans is reevaluated, considering that a decrease in urate excretion induced by drugs like pyrazinamide or by endogenous compounds like lactate and ketone bodies might be a result of stimulation of urate reabsorption and not, as previously considered, of inhibition of urate secretion.

IDENTIFICATION OF CARCINOGENIC TRP-P-2 AND-1 IN THE EFFLUENT FROM A SEWAGE TREATMENT PLANT

It has been identified that the origin of the heterocyclic amines, a group of suspected human carcinogens is high-temperature heating of proteinaceous materials, e. g., food and plants (tabacco-leaves and woods). The heterocyclic amines have been found in human excretions and rain water. We extracted two of these heterocyclic amines, 3-amino-1-methyl-5H-pyrido[4, 3-b]indole (Trp-P-2) and 3-amino-1, 4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P-1) in the water of a sewage teatment plant in Japan by HPLC analysis. The concentration of Trp-P-2 and-1 were estimated at about 10-2μg/L, each. The presence of these compounds shows the possible widespread pollution of surface waters with this class of carcinogens.

The effects of human burn injury on urinary nitrate excretion

Different studies have demonstrated both an increase and a decrease in the biosynthesis of nitric oxide (NO) during the first 2 days following experimental and human burn trauma. This study investigated changes in urinary nitrate excretion in humans following thermal injury in order to determine the temporal relationship between NO release and the initial injury. Urinary nitrate was measured in daily 24-h urine collections taken on days 1–7 following burn injury from 15 patients. The control group consisted of 11 healthy, age- and sex-matched patients who kept a nitrate-restricted diet for five days prior to collection of a single 24-h urine sample. The burns group had a mean age of 41.9±19.4 (mean±S.D.) years and a mean total burn surface area (TBSA) of 30.2±24.9% (mean±S.D.). In the burn injured patients, urinary nitrate levels peaked at day 4 and a 2-fold increase relative to day 1 was observed. Urinary nitrate levels were significantly higher in the burns group than the control group on days 4 and 5 only ( p<0.05 for both days). There was no correlation between TBSA and the measured urinary nitrate levels. This study confirms that the biosynthesis of NO is increased during the first week following burn trauma and establishes that the renal elimination of the by-products of NO metabolism is not increased during the first three days after injury. Notwithstanding the potential effects of burns on nitrate distribution, our findings may reflect a delay in the release of NO following the initial insult.

A human capecitabine excretion balance and pharmacokinetic study after administration of a single oral dose of 14C-labelled drug.

An excretion balance and pharmacokinetic study was conducted in cancer patients with solid tumors who received a single oral dose of capecitabine of 2000 mg including 50 microCi of 14C-radiolabelled capecitabine. Blood, urine and fecal samples were collected until radioactive counts had fallen to below 50 dpm/mL in urine, and levels of intact drug and its metabolites were measured in plasma and urine by LC/MS-MS (mass spectrometry) and 19F-NMR (nuclear magnetic resonance) respectively. Based on the results of the 6 eligible patients enrolled, the dose was almost completely recovered in the urine (mean 95.5%, range 86-104% based on radioactivity measurements) over a period of 7 days after drug administration. Of this, 84% (range 71-95) was recovered in the first 12 hours. Over this time period, 2.64% (0.69-7.0) was collected in the feces. Over a collection period of 24-48 h, a total of 84.2% (range 80-95) was recovered in the urine as the sum of the parent drug and measured metabolites (5'-DFCR, 5'-DFUR, 5-FU, FUH2, FUPA, FBAL). Based on the radioactivity measurements of drug-related material, absorption is rapid (tmax 0.25-1.5 hours) followed by a rapid biphasic decline. The parent drug is rapidly converted to 5-FU, which is present in low levels due to the rapid metabolism to FBAL, which has the longest half-life. There is a good correlation between the levels of radioactivity in the plasma and the levels of intact drug and the metabolites, suggesting that these represent the most abundant metabolites of capecitabine. The absorption of capecitabine is rapid and almost complete. The excretion of the intact drug and its metabolites is rapid and almost exclusively in the urine.

Iodine supplementation of laying hen feed: A supplementary measure to eliminate iodine deficiency in humans?

Iodine deficiency still exists in many countries worldwide, to a certain degree this is also true for Germany. Food of animal origin can be a good source for iodine depending on the feed. To investigate the possible use of laying hen feed enriched with iodine, we conducted a feeding experiment with 40 laying hens receiving feed with different amounts of iodine either as KIO3 or in the form of seaweed. Iodine concentration in eggs increased significantly depending on iodine intake after a 2 week period. Seaweed could also be used as an iodine source by the hens. A subsequent consumption study with 24 volunteers showed that eggs enriched with iodine can increase human's iodine excretion and therefore improve human's iodine supply. This new strategy is thought to accompany salt iodization programs, not to replace them.

Nutrition and osteoporosis.

Nutritional factors have a significant influence on the cause of osteoporosis. Calcium supplementation may be particularly effective in populations with a low calcium diet. Supplementations of 500 mg/d may produce about 4% gain in skeletal calcium in adolescents. Supplementations of 800 mg/d may prevent bone loss in postmenopausal women. The results of clinical trials also suggested that such supplementation may prevent hip and vertebral fractures in the elderly. The largest effect of calcium supplementation occurs in the first year of treatment, whereas sustained effects are not proven. Vitamin D supplementation may be particularly useful in vitamin D-deficient elderly. In this group, hip fractures may be prevented by vitamin D administration. Urinary sodium excretion is correlated with urinary calcium excretion in humans, and a direct effect of high sodium intake on loss at the hip has been demonstrated. Observational epidemiologic studies suggested a negative effect of a high protein intake on bone density, although there are no results from clinical trials to support this view. Dietary fiber, phytate, oxalate, and caffeine intake may have a small negative effect on calcium absorption.

Effects of Niravoline (RU 51599), a Selective Kappa–Opioid Receptor Agonist on Intracranial Pressure in Gradually Expanding Extradural Mass Lesion

It has recently been reported that kappa-opioid receptor agonists inhibit antidiuretic hormone secretion and promote water excretion in humans and animals. We investigated the effect of niravoline (RU 51599), a selective kappa-opioid receptor agonist in the treatment of intracranial hypertension. Acute intracranial hypertension was induced in cats by continuous inflation of an extradural balloon with physiological saline at the constant rate of 0.5 ml/h for 3 h. At this point, inflation was discontinued and the balloon remained expanded for an additional hour after which it was deflated. In the post-deflation period, monitoring continued for 1 h. The control group (n = 8) received ringer's lactate solution only, while the treatment group (n = 8) received an intravenous (IV) injection of 1.0 mg/kg of niravoline, every hour at the beginning of balloon inflation, during balloon inflation, in post-inflation, and at deflation time (5 doses). Changes in intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), electroencephalogram (EEG), blood gases, pupil size, serum electrolytes, and osmolality were measured in both groups. Brain water content was determined in a separate group of cats at the end of a 3-h extradural brain compression. Compared to the untreated group, the niravoline-treated group had a significantly lower ICP and higher CPP at the 2 and 3 h during balloon inflation, in post-inflation, and in post-deflation periods. Brain water content was significantly reduced in niravoline-treated animals. No significant change was observed in serum osmolality throughout the experiment. Our results indicate that the mechanism by which niravoline reduces ICP is partly via a reduction in brain water content. Also, the current findings suggest that in clinical situations in which ICP is elevated due to the pressure of an extradural mass, niravoline may effectively reduce ICP while maintaining adequate CPP until the mass is removed.

Quantitative studies of human urinary excretion of uropontin

Uropontin is the urinary form of osteopontin, an aspartic acid-rich phosphorylated glycoprotein. Uropontin has been previously shown to be a potent inhibitor of the nucleation, growth and aggregation of calcium oxalate crystals and the binding of these crystals to renal epithelial cells. Quantitative data defining the excretion of this protein are necessary to determine its role in urinary stone formation. In the present studies, we determined uropontin excretion rates of normal humans. Urine samples were obtained under conditions of known dietary intake from young adult human volunteers with no history, radiographic or laboratory evidence of renal disease. Urinary concentrations of uropontin were measured by a sensitive ELISA employing an affinity purified polyclonal antiserum to uropontin. Thirteen normal subjects ingested a constant diet providing 1 gram of calcium, 1 gram of phosphorus, 150 mEq of sodium and 1 gram of protein per kilogram of body wt per day during an eight day study period. The relationship of urinary volume to uropontin excretion was assessed by varying fluid intake on the last four days of the study to change the mean urine volume/24 hr by > 500 ml. Urine collected in six hour aliquots for eight days was analyzed for uropontin by ELISA, and for calcium, and creatinine. Daily uropontin excretion of 13 individual subjects was 3805 +/- 1805 micrograms/24 hr (mean +/- 1 SD). The mean urinary levels (1.9 micrograms/ml) detected in the present study are sufficient for inhibition of crystallization; our previous studies have demonstrated that the nucleation, growth and aggregation of calcium oxalate crystals and their binding to renal cells in vitro are inhibited by this concentration of purified uropontin. In contrast to the regular pattern of diurnal variation of calcium excretion seen in most subjects, uropontin excretion showed no regularity of diurnal variation and was not directly related to either calcium or creatinine excretion or changes in urinary volume. However, uropontin concentration varied inversely with urine volume (P < or = 0.001), so that the highest uropontin concentrations occurred when urine volume was the lowest. We conclude that the physiologic characteristic of an inverse relationship of uropontin concentration to urine volume favors protection from urinary crystallization of calcium oxalate by uropontin. Our quantitative definition of urinary uropontin excretion of normal adults provides the basis for the evaluation of uropontin excretion by individuals who have formed urinary stones.

A role for granulomatous inflammation in the transmission of infectious disease: schistosomiasis and tuberculosis.

The relationship between cell-mediated granulomatous inflammation and transmission of disease in schistosomiasis and tuberculosis has been explored. In 2 experiments involving Schistosoma mansoni-infected normal and T cell-deprived mice, and infected deprived mice that had been variously reconstituted with immune or normal lymphocytes or immune serum, there was a significant positive numerical correlation between mean liver granuloma diameters and faecal egg counts in individual animals. Lymphocytes from donors with recently patent infections were more active than cells from chronically infected or uninfected donors in reconstituting egg excretion rates in deprived recipients, and mesenteric lymph node (MLN) cells were more active than spleen cells. Modulation of granulomatous activity with increasing chronicity of infection in the donors, resulting in a decrease in granuloma size around freshly produced tissue-bound eggs, was paralleled by a waning of the capacity of transferred lymph node cells to reconstitute egg excretion in the recipients. Serum taken from chronically infected donor mice over the same period and transferred to infected deprived recipients became more active in enhancing egg excretion in the recipients as the cell-mediated activity declined. A recent study in Kenya has found that S. mansoni-infected patients with concurrent human immunodeficiency virus (HIV) infection excrete fewer eggs than patients exposed to the same levels of schistosome infection, but who are not HIV-infected, thus indicating that schistosome egg excretion in humans is also immune-dependent. Attention is drawn to an apparently parallel situation in human tuberculosis, another pathogen which induces a cell-mediated granulomatous immune response. Several studies have shown that patients with tuberculosis who are also HIV-seropositive tend to have fewer tubercle bacilli detectable in their saliva than those with tuberculosis, but who are HIV-negative. This discrepancy, associated with differences in lung pathology in HIV-positive patients, suggests that in tuberculosis immune cell-mediated granulomatous inflammation causes the destruction of host tissue in a manner which facilitates onward transmission of the bacterial pathogen.

Urinary isoflavonoid excretion in humans is dose dependent at low to moderate levels of soy-protein consumption

Soybeans contain isoflavones, which have been associated with many health benefits, including decreased cancer risk. The purpose of our study was to measure urinary isoflavonoid excretion in response to daily consumption of soy that contained 0-36 mg isoflavones--a lower range than used in previous studies--and to compare urinary isoflavonoid excretion between equol excreters and nonexcreters. Fourteen men and women aged 20-40 y participated in the study. Half of the subjects were identified previously as equol excreters and the other half as equol nonexcreters. This randomized, double-blind, crossover study consisted of four 9-d diet treatment periods. During each treatment period participants consumed a low-photoestrogen controlled diet and a beverage containing 0, 5, 10, or 20 g soy protein. Urine collected on the last 3 d of each treatment period was analyzed for isoflavonoid (equol, O-desmethylangolensin, genistein, and daidzein) and lignan (enterodiol and enterolactone) contents by using isotope-dilution gas chromatography-mass spectrometry. There was a highly linear dose response of urinary isoflavonoid excretion to soy consumption, which did not differ significantly between equol excreters and nonexcreters. There were no significant differences in lignan excretion between the two diet treatments. Our results indicate that urinary isoflavonoid excretion is dose dependent in humans at low to moderate levels of soy consumption.

Hypertension and identification of toxin in human urine and serum following a cluster of mussel-associated paralytic shellfish poisoning outbreaks

Following four outbreaks of paralytic shellfish poisoning on Kodiak Island, Alaska, during 1994, medical records of ill persons were reviewed and interviews were conducted. Urine and serum specimens were analyzed at three independent laboratories using four different saxitoxin binding assays. High-performance liquid chromatography was used to determine the presence of specific toxin congeners. Among 11 ill persons, three required mechanical ventilation and one died. Mean peak systolic and diastolic blood pressure measurements were 172 (range 128–247) and 102 (range 78–165) mmHg, respectively, and blood pressure measurements corresponded with ingested toxin dose. All four different laboratory methodologies detected toxin in serum at 2.8–47 nM during acute illness and toxin in urine at 65–372 nM after acute symptom resolution. The composition of specific paralytic shellfish poisons differed between mussels and human biological specimens, suggesting that human metabolism of toxins had occurred. The results of this study indicate that saxitoxin analogues may cause severe hypertension. In addition, we demonstrate that saxitoxins can be detected in human biological specimens, that nanomolar serum toxin levels may cause serious illness and that human metabolism of toxin may occur. Clearance of paralytic shellfish poisons from serum was evident within 24 hr and urine was identified as a major route of toxin excretion in humans.

Origins of the Sex Difference in Human Urinary Free Cortisol Excretion

Origins of the Sex Difference in Human Urinary Free Cortisol Excretion

Effect of Repeated Exercise on Urinary 8-Hydroxy-deoxyguanosine Excretion in Humans

The purpose of this study was to investigate the effect of repeated exercise on oxidative damage to DNA in 10 well trained long distance runners who participated in an 8-day training camp. The average running distance during the camp was 30 ± 3 km/day. The amount of urinary 8-hydroxy-deoxyguanosine (8-OHdG) excretion was used to estimate the oxidative DNA damage. Urine samples were collected for both a 3-day control peRíod as well as throughout the camp. Blood samples were drawn after overnight fasting both before and after the camp. Urinary 8-OHdG excretion was significantly increased during the camp compared to the control peRíod (265.7 ± 75.5 vs. 335.6 ± 107.4 pmol/kg/day, P < 0.05). The content of 8-OHdG in the lymphocyte DNA on the day after finishing the camp did not differ from that before the camp. Plasma TBARS, LDH, CK, CK-MB, and myoglobin significantly rose after the camp (P < 0.05). The plasma β-carotene levels tended to rise after the camp, while the plasma α-tocopherol levels increased significantly after the camp (P < 0.05). These results indicate that repeated exercise augments oxidative stress and that DNA is also injured by exercise-induced reactive oxygen species. However, the oxidative damage to DNA is not accumulated by consecutive exercise, although it is sustained as long as the exercise is repeated.

26] α-carboxyethyl-6-hydroxychroman as urinary metabolite of vitamin E

Publisher Summary This chapter describes methods for the identification and estimation of urinary 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman ( α -CEHC) suitable to further investigate the conditions for α -CEHC excretion in humans and animals. α -CEHC is excreted as a sulfate or glucuronic acid conjugate. These conjugates must be hydrolyzed before determination to yield either the methyl esters or the free metabolites. Hydrolysis with a glucuronidase/sulfatase mixture leads to free α -CEHC. Due to the lack of a standard α -CEHC conjugate, it is not possible to test the recovery of α -CEHC released from conjugates. The conditions of enzymatic hydrolysis are therefore varied to determine if they are optimal. Increasing amounts of enzyme are used to hydrolyze a fixed amount of urine powder for increasing times, and the resulting α -CEHC is measured by means of gas chromatography/mass spectrometry (GC/MS). The hydrolysis of α -CEHC conjugates with methanolic HCl has been used to esterify the carboxylic acid derivatives of α -tocopherol and prevent lactonization.