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Urinary excretion of vasoactive factors are correlated to sodium excretion.

BACKGROUND: The relationship between urinary vasoactive factors and sodium excretion has not been adequately addressed in humans. PROCEDURE: Excretion rates of sodium, nitrates/nitrites (NOx), cGMP, and endothelin-1 (ET-1) were measured before and after ingestion of a mixed electrolyte solution (8 oz Gatorade) while undergoing a routine cardiovascular evaluation in a sample of 51 normotensive young adults. RESULTS: Significant correlations were detected for changes in excretion between all four variables, r ranged from 0.50 to 0.86 (P < .001). Correlations were higher in African Americans than white Americans. CONCLUSIONS: The association of renal ET-1 and NO activity with sodium excretion supports the hypothesis that these factors play a role in the physiologic response to acute changes in sodium intake, particularly in African Americans.

Adolescent↗

Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample.

Experimental models suggest that increased aldosterone and sodium intake are associated with renovascular damage and resultant proteinuria. We hypothesized that serum aldosterone and urinary sodium would be associated with urinary albumin excretion, an indicator of kidney damage. We evaluated 2700 participants (53% women, mean age 58 years) from the Framingham Offspring Study who attended a routine examination between 1995 and 1998, who were free of heart failure and renal failure, and underwent testing for serum aldosterone, spot urinary sodium, and urinary albumin excretion (urine albumin/creatinine ratio, UACR), the latter two indexed to urinary creatinine. Stepwise multivariable linear regression was used to evaluate the relations between UACR with urinary sodium index and serum aldosterone. In multivariable regression, log urinary sodium index was associated positively with log-UACR (P<0.0001). UACR levels in the fourth and fifth quintiles of urinary sodium index were 24% (95% confidence interval (CI) 3-49%), and twofold higher (95% CI 72-150%), respectively, relative to the lowest quintile (P-value for trend across quintiles <0.001). In multivariable models, log-transformed aldosterone was not related to log-UACR. The top quintile of serum aldosterone levels was associated with a 21% higher (95% 1-44%) UACR levels relative to the lowest quintile. Urinary albumin excretion was strongly and positively associated in a continuous fashion with urinary sodium excretion, whereas a weaker nonlinear positive relation with serum aldosterone was noted. Our cross-sectional observations raise the possibility that dietary salt intake may be associated with early renovascular damage.

Albuminuria↗

The maximum capacity of the bovine liver to excrete manganese in bile, and the effects of a manganese load on the rate of excretion of copper, iron and zinc in bile.

1. The maximum capacity of the bovine liver to excrete manganese in bile was determined in three Friesian-cross steers surgically prepared to allow bile flow-rate to be measured and samples collected. Plasma Mn concentrations were increased by infusing manganese chloride solutions into a jugular vein and the biliary excretion rates of Mn, copper, zinc and iron were measured. 2. The maximum capacity of the liver to excrete Mn in bile was exceeded at an infusion rate of approximately 4000 microgram Mn/min, and at this rate there was a significant decrease in the concentration of Cu, Fe and Zn in bile. The maximum concentration (mean +/- SE) of Mn in bile was 193 +/- 19 microgram/ml, and the maximum excretion rate (mean +/- SE) was 1210 +/- 130 microgram/min for three animals. There was no reduction in bile flow or evidence of live damage as a result of the infusions.

Animals↗

Biliary excretion of cadmium in rat. I. Dose-dependent biliary excretion and the form of cadmium in the bile.

Biliary excretion of cadmium was studied in rats after intravenous injection of different doses of cadmium chloride (0.1-2 mg Cd/kg). The rate of bile flow was not affected by cadmium injection and cadmium was excreted into bile during the first 2 hr after injection. The biliary excretion of cadmium increased with increasing dose of CdCl2. Cumulative biliary excretion of cadmium for 5 hr was 0.065% of the administered dose for groups injected with 0.1 mg Cd/kg as compared to 16.9% of the administered dose for 2 mg Cd/kg. During the 5 hr experimental period, most of the cadmium in liver cytosol was bound to high-molecular-weight proteins and less than 10% was bound to the metallothionein fraction. The biliary cadmium was recovered as a low-molecular-weight compound (less than 4,000) in experiments with various doses of cadmium and no cadmium was attached to high-molecular-weight proteins or metallothionein in the bile. The low-molecular-weight cadmium complex in bile was partially characterized as Cd-glutathione by thin-layer chromatography and amino acid analysis.

Animals↗

Dietary psyllium increases fecal bile acid excretion, total steroid excretion and bile acid biosynthesis in rats.

Psyllium, a source of dietary fiber rich in soluble components results in lower serum cholesterol concentration in several species. Suggested mechanisms for the hypocholesterolemic effect include a greater excretion of fecal bile acids and total steroids, and up-regulation of bile acid biosynthesis. The activity of cholesterol 7alpha-hydroxylase (7alphaOHase), the rate limiting enzyme in bile acid biosynthesis, is higher in rats fed 5% psyllium. Whether this higher activity corresponds to an increase in mRNA levels has not been determined. Four groups of 10 rats were fed a semipurified diet containing 5% cellulose (CEL; control), 5% cellulose plus 1% cholic acid (CCA), 5% cellulose plus 2% cholestyramine (CHY) or 5% psyllium hydrocolloid (PSY) for 3 wk. Liver cholesterol concentration, fecal bile acid and total steroid excretion, 7alphaOHase activity and 7alphaOHase mRNA levels were measured. Liver cholesterol content in rats fed CCA was significantly higher than in all other groups. Rats fed CHY and PSY had significantly lower liver cholesterol content than those fed CEL. Total fecal steroid and bile acid excretions were significantly greater in rats fed CCA, CHY and PSY than in those fed CEL. Activities and mRNA levels of 7alphaOHase in rats fed CHY and PSY were significantly higher than in rats fed CEL or CCA. These data indicate that feeding psyllium to rats increases fecal bile acid and total steroid excretion as well as 7alphaOHase activity and 7alphaOHase mRNA levels.

Animals↗

High urinary excretion of uric acid combined with high excretion of calcium links kidney stone disease to familial hypertension.

BACKGROUND: Past studies identified an association between kidney stone disease (KSD) and hypertension. We recently reported a high occurrence of hypertension in families of patients with hyperuricosuric KSD. As hypercalciura frequently coexists with hyperuricosuria and high urinary excretion of calcium is found in patients with hypertension, we hypothesized that hyperuricosuria that is accompanied by hypercalciuria better describes the familial association between KSD and hypertension. METHODS: Four hundred and eighty-six KSD patients, aged 18-50 years, attending a lithotripsy unit collected a 24-h urine sample for metabolic analysis and provided information on family history of hypertension. The familial occurrence of hypertension was compared among four groups of patients: those who had combined elevation of both urinary calcium and uric acid excretions ("combined" abnormality, n=56), those who had hyperuricosuria without concomitant hypercalciuria ("pure" hyperuricosuria, n=67), those who had hypercalciuria without concomitant hyperuricosuira ("pure" hypercalciuria, n=52), and a control KSD patient group ("other" abnormality, n=311). The prevalence of treated hypertension in patients from the four groups was 16%, 12%, 2%, 10%, respectively. RESULTS: Thirty-four per cent of the patients with the "combined" abnormality had a positive family history of hypertension, defined as two or more first-degree relatives with treated hypertension, that was significantly higher than in patients with either "pure" hyperuricosuira (15%, P<0.02), "pure" hypercalciuria (8%, P<0.001), or patients with "other" abnormality (10%, P<0.001). The adjusted OR for positive family history of hypertension in the "combined" abnormality group compared to the control KSD patient group was 5.6 (2.39-13.30). The prevalence of hypertension in siblings of patients with the "combined" abnormality (13%) was significantly higher than in siblings of patients with either "pure" hyperuricosuria (3%, P<0.001), "pure" hypercalciuria (1%, P<0.001), or siblings of control patients with "other" abnormality (4%, P<0.001). The adjusted OR for hypertension in siblings of a patient with "combined" abnormality compared to a control KSD patient was 3.4 (1.97-5.91). Patients in the "combined" abnormality group were also characterized by significantly elevated urinary sodium, phosphorus, citrate and potassium excretions. CONCLUSIONS: Our data suggest that there is a strong, independent association between familial occurrence of hypertension and the phenotype characterized by combined elevation of both urinary uric acid and calcium excretions. The association is not present in those with "pure" hyperuricosuria or "pure" hypercalciuria. Ascertainment of patients based on this phenotype may identify more homogeneous populations for genetic analysis of hypertension.

Adult↗

Sodium excretion in relation to sodium intake and aldosterone excretion in newborn pre-term and full-term infants.

The importance of aldosterone for the control of salt balance has been examined in pre-term infants (gestational age 28--34 weeks) and in full-term infants. The post-natal age has varied from 2--21 days. Eight-hour urinary specimens have been analysed with regard to sodium, potassium and aldosterone. The daily sodium intake has been recorded following determination of milk intake and analyses of sodium in breast milk. Due to variations of sodium content of breast milk, the daily sodium intake in pre-term infants was lower than in full-term infants during the first 10 days of life. The sodium excretion was significantly higher in pre-term infants than in full-term infants during the first six days of life. During the first week of life the sodium balance is negative in pre-term infants and positive in full-term infants. Aldosterone excretion is high during the first week of life and increases further from the 2nd to the 3rd week of life in both pre-term and full-term infants. The correlation between aldosterone excretion and urinary potassium/sodium quotient is 0.87 in full-term infants, 0.57 in pre-term infants aged 13--20 days and does not exist in pre-term infants aged 2--10 days. It is suggested that the high sodium excretion in newborn pre-term infants can in part be explained by an unresponsiveness to aldosterone at this developmental stage.

Aldosterone↗

Urinary excretion of inorganic pyrophosphate by normal subjects and patients with renal calculi in north-western India and the effect of diclofenac sodium upon urinary excretion of pyrophosphate in stone formers.

24 h urinary pyrophosphate excretion was studied in 20 normal healthy subjects and 75 idiopathic stone formers from north-western regions of India. The mean 24-hour urinary excretion of pyrophosphate was significantly low in stone formers (50.67 +/- 2.16 mumol/24 h) as compared to that of normal subjects (71.46 +/- 5.46 mumol/24 h) (p less than 0.01). Diclofenac sodium, a non-steroidal anti-inflammatory agent, was administered 50 mg thrice daily for 1 week to 18 stone formers and 24-hour urinary pyrophosphate excretion was studied before and after drug therapy. The 24-hour urinary excretion of pyrophosphate increased from 54.32 +/- 21.40 to 78.31 +/- 28.03 mumol subsequent to diclofenac sodium therapy (p less than 0.01).

Adult↗

The circadian rhythm of renal excretion in the rat: relationship between electrolyte and corticosteroid excretion.

In the rat, a circadian rhythm can be demonstrated in plasma levels and in urinary excretion rates of aldosterone and of corticosterone, reflecting rhythmic variations in adrenocortical secretion. There is also a circadian rhythm in the urinary excretion rates of sodium and of potassium in rats with unrestricted food consumption. The rhythmic pattern of potassium excretion seems to be controlled by the rhythm of corticosterone and/or aldosterone, whereas the rhythmic pattern of sodium excretion seems to be independent of adrenocortical secretion.

Aldosterone↗

Excretion of urinary cadmium, copper, and zinc in cadmium-exposed and nonexposed subjects, with special reference to urinary excretion of beta2-microglobulin and metallothionein.

The objectives of this study were to examine the association between urinary excretion of cadmium (U-Cd), copper (U-Cu), and zinc (U-Zn) and the severity of two different indicators of renal toxicity (urinary excretion of beta2-microglobulin [U-beta2-MG] and metallothionein [U-MT]) in Cd-exposed subjects compared to controls, and to assess the physiologic mechanisms by which the exposure to environmental Cd affects U-Cd, U-Cu, and U-Zn. The target population included 3508 Cd-exposed and 294 nonexposed participants who received a health survey conducted among the population of the Kakehashi River basin. Increases of U-Cd, U-beta2-MG, and U-MT in the Cd-exposed population were observed relative to excretion of these substances in controls. Regression analysis using a general linear model revealed that the correlations between U-Cd or U-Cu, and U-beta2-MG and between U-Cd, U-Cu or U-Zn, and U-MT were statistically significant in both sexes, but the correlation between U-Zn and U-beta2-MG excretion was significant only in men. These results suggest U-Cd and U-Cu is affected by dysfunction in renal tubular absorption (indicated by U-beta2-MG), whereas not only U-Cd and U-Cu but also U-Zn appear to be a function of renal cellular desquamation (indicated by U-MT).

Aged↗

[Urine C-peptide excretion in hypocaloric states and factors affecting its excretion].

Recent evidence suggests that hyperinsulinemia may contribute to the development of various risk factors of atherosclerosis. To examine the effects of energy intake on insulin secretion, 24-h urine C-peptide was measured in twelve women with rheumatoid arthritis who were not taking any medicine and stayed in Koda hospital for a diet therapy which lasted 55 days. They were basically placed on a 1200 kcal/day vegan diet combined with three 3-5-day fasting periods (200 kcal/day). Urine C-peptide excretion markedly decreased from 31-40 to 8-14 micrograms/day during the fasting periods. Among the anthropometric variables examined, the average level of urine C-peptide excretions measured in the fasting periods showed a significant correlation with the percentage and the amount of body fat. However, such correlation was not observed while the calorie intake was 1200 kcal. No clinical laboratory parameter showed a significant correlation with urinary C-peptide excretion. These results suggest that the major determinant of urine C-peptide excretion is food intake and that hyperinsulinemia could be easily improved by restricting energy intake.

Arthritis, Rheumatoid↗

[Alanineaminopeptidase excretion in the urine and osmotic neophropathy. Studies on the diagnostic meaning and pathophysiology of elevated alanineaminopeptidase excretion after use of radiologic contrast media for the kidneys].

In patients with several internal diseases the percental change of the excretion of the alanine aminopeptidase with the urine 18--20 hours after intravenous injection of the X-ray contrast medium Visotrast going through the kidneys correlates with the change after infusion of Mannitol (r = 0.98, p less than 0.001) and of Dextran (r = 0.82, p less than 0.01). The osmotic nephropathy is to be regarded as a common cause of an increased enzyme excretion, which appears after application of hypertonic solutions especially in preexisting renal diseases. While the excretion of alanine aminopeptidase in persons with healthy kidneys changes only unessentially, in patients with diffuse nephropathies after the application of these drugs there appear diagnostically relevant increases of excretion.

Aminopeptidases↗

Four-hour measurement of urinary iron excretion after deferoxine treatment: a rapid, simple method for study of iron excretion.

In a group of 56 patients being evaluated for iron storage disease, all of whom underwent liver biopsy with quantitative measurement of liver iron concentration, urinary excretion of iron was measured following intramuscular injection of deferoxamine (10 mg/kg body weight). Urine was collected in two portions, 0-4 h and 4-24 h after deferoxamine administration. Iron excretion in the first 4 h was closely correlated to that over the entire 24-h period (r = 0.88, p less than 0.0001, 95% confidence interval = 0.80-0.93), indicating that the 4-h deferoxamine urinary excretion test can be adapted readily to an outpatient clinical setting, helping to insure complete and accurate urine collections. Correlation of 0- to 4-h urinary iron excretion and quantitative liver iron (r = 0.335), although higher than for the full 24 h (r = 0.192), was not sufficient to accurately predict hepatic iron concentration in the individual patient.

Deferoxamine↗

[An experimental study on the biliary excretion of ceftizoxime in the presence and after relief of biliary obstruction with special reference to the influence of bile acid metabolism on the biliary excretion of the antibiotic].

The biliary excretion of ceftizoxime (CZX) in the presence and after relief of biliary obstruction was experimentally investigated in twelve dogs. In the presence of biliary obstruction, the biliary excretion of CZX was impaired and, immediately after relief of biliary obstruction, the existence of reverse shunt from the vascular system to the biliary tract was suggested. After relief of biliary obstruction, the biliary excretion of CZX and the ratio of [lithocholic acid + deoxycholic acid]/[cholic acid + chenodeoxycholic acid] in the bile were impaired in one group with external drainage as compared to the other group with internal drainage. It was experimentally proved that the biliary excretion of antibiotics seemingly related very closely to the bile acid metabolism and that it was increased by administration of the bile acid after external drainage or by normalization of the enterohepatic circulation of the bile acid after internal drainage.

Animals↗

Effect of some chelating agents on the biliary excretion of mercury. 2. Relationship between the excretion of mercury and its binding to bile fractions.

Mercury binding to bile components and the correlation between the amount of mercury bound in the bile fraction 2 and the rate of mercury biliary excretion were studied in female rats exposed to intravenously injected HgCl2 after pretreatment with a series of 14 chemical agents. After pretreatment with the tested agent, 203Hg was detectable both in the bile fraction 1 and 2. Distribution pattern of 203Hg between the two fractions appeared to be linked with the chemical structure of the formed mercury complex. Pretreatment with these agents did not inhibit the formation of the bile fraction 3. By their influence on the 203Hg distribution between the bile fractions 1 and 2, the tested agents can be roughly divided into 3 groups: the content of 203Hg in the bile fraction 2 is about 10--20% and does not change significantly within the first 24 hours after 203 HgCl2 injection (cysteine, penicillamine, disodium ethylenediaminotetraacetate -- Na2EDTA, sodium diethyldithiocarbamate, sodium alanindithiocarbamate, acrylonitrile); the the 203Hg content in the bile fraction 2 increases (thiophenolacetate); the content of 203Hg in fraction 2 is initially several times higher than that in the bile fraction 1, but then decreases during the first 24 hours (2,3-dimercaptopropanol -- BAL, sodium 2,3-dimercaptopropanesulphonate, spironolactone, Thiomestron). The rate of mercury biliary excretion (Rb) was found to be closely correlated with the relative amount of mercury present in the bile fraction 2 (a2), if a2 > 30%, both in vivo (Rb = 1.077 a2 + 0.758) and invitro (Rb = 1.067 a2 + 0.519) experiments. Practically identical values of the constant accompanying a2 in the two equations seem to indicate that one of the decisive factors influencing the rate of mercury biliary excretion in rats is rather the mercury affinity for the bile fraction 2 components than the agent-induced mercury transport mechanisms. For a2 < 30% the correlation is non-linear and the excretion is rather inhibited than enhanced.

Animals↗

Effect of some chelating agents on the biliary excretion of mercury. 1. Excretion kinetics and distribution of mercury in the organism.

Wistar strain female rats were used to study the impact of 1-cysteine,D,L-penicillamine, EDTA, sodium N,N-diethyldithiocarbamate, BAL, Unitiou, Spironolactone, Thiomestron and thiophenolacetate on excretion kinetics and distribution pattern of 203Hg injected intravenously in a dose of 120 microgram 203Hg2+ per rat. A considerably enhanced biliary excretion of mercury was observed after pretreatment with Spironolactone, Unitiol, BAL and Thiomestron. The action of these agents persisted for only 2--3 hours after mercury application. The highest urinary excretion of mercury was recorded after pretreatment with Unitol and BAL. All the tested agents, particularly thiophenolacetate, turned out to enhance mercury excretion through intestinal wall cells. Pretreatment with the tested agents caused also considerable changes in the pattern of mercury distribution in the rat organism.

Animals↗

Metabolism and excretion of trovafloxacin, a new quinolone antibiotic, in Sprague-Dawley rats and beagle dogs. Effect of bile duct cannulation on excretion pathways.

The excretion and metabolism of trovafloxacin was investigated after administration of a single oral dose of [14C]trovafloxacin to Sprague-Dawley rats and beagle dogs. The bile was the major route of excretion in rats (59% of the dose). Trovafloxacin was extensively metabolized in this species, and only 3% of the dose was excreted unchanged. Glucuronidation and acetylation were the major metabolic pathways involved in the elimination, and no oxidative metabolites were detected in rats. In dogs, 97.6 and 2.7% of the dose was recovered in feces and urine, respectively, in 72 hr. However, excretion studies in bile duct-cannulated dogs revealed that 28.2% of the radioactivity was recovered in bile, whereas 45.6% was in urine. This suggested that bile duct cannulation had affected the disposition of trovafloxacin. Analysis of bile and urine of bile duct-cannulated dogs by LC/MS/MS indicated that glucuronidation was the major metabolic pathway in dogs as well. Two novel metabolites were identified in the bile of this species. One was confirmed as a pyrroline analog of trovafloxacin (M7), and the second was tentatively identified as the hydroxycarboxylic acid analog (M6). The differences in metabolism of trovafloxacin in the bile duct-cannulated and noncannulated dogs were investigated by comparison of the metabolite profiles in urine and feces of these animals. Although the metabolites in urine were similar, the extracts of fecal samples obtained from noncannulated animals revealed the presence of N-acetyltrovafloxacin (M3). Incubation of trovafloxacin with cecal contents of dogs under anaerobic conditions suggested the involvement of intestinal microflora in the formation of this metabolite. Metabolite M3 was absent from fecal extracts of bile duct-cannulated dogs, suggesting that surgery had affected the metabolism of trovafloxacin by gut microflora.

Animals↗

Absorption, distribution, metabolism, and excretion of furosemide in dogs and monkeys I: analytical methodology, metabolism, and urinary excretion.

35S-Furosemide was administered to beagle dogs and rhesus monkeys in an oral solution on a single and a 20 repeated 5-mg/kg/day dosing regimen. Following the single dose, 25.0% (dogs) and 24.0% (monkeys) of the dose were excreted in the urine in 24 hr. TLC analysis demonstrated that both species had similar excretory patterns; i.e., over 80% of the amount excreted in the urine was present as unchanged durosemide and the remainder was composed of a known metabolite, saluamine, and an as yet unidentified metabolite(s). The repetitive dosing regimen did not appear to alter significantly either the total amount recovered in the 24-hr urine or the excretion pattern. Studies in dogs showed that only 50-60% of furosemide was absorbed from oral solution. A significant biliary secretion elimination pathway for furosemide also was observed.

Animals↗