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PubMed2005

Greatly elevated urea excretion after air exposure appears to be carrier mediated in the slender lungfish (Protopterus dolloi).

Under aquatic conditions, Protopterus dolloi is ammoniotelic, excreting only small amounts of urea-N. However, upon return to water after 30 d estivation in air, the lungfish excretes only small amounts of ammonia-N but massive amounts of urea-N. A similar pattern is seen after 21-30 d of terrestrialization, a treatment in which the lungfish is air exposed but kept moist throughout. After both treatments, the time course of urea-N excretion is biphasic with an immediate increase, then a fall, and finally a second larger increase that peaks at about 12 h and may be prolonged for several days thereafter. Urea-N excretion rates during the second peak reach 2,000-6,000 micromol N kg(-1) h(-1), two to three orders of magnitude greater than rates in most fish and comparable only to rates in species known to employ UT-A type facilitated diffusion urea transporters. Divided chamber studies and measurements of the clearance rates of [3H]-PEG-4000 (a glomerular filtration and paracellular diffusion marker) and two structural analogs of urea ([14C]-acetamide and [14C]-thiourea) were performed to characterize the two peaks of urea-N excretion. The smaller first peak was almost equally partitioned between the head (including internal and external gills) and the body compartment (including urinary opening), was accompanied by only a modest increase in [14C]-acetamide clearance equal to that in [14C]-thiourea clearance, and could be accounted for by a large but short-lasting increase in [3H]-PEG-4000 clearance (to about fivefold the terrestrial rate). The delayed, much larger second peak in urea-N excretion represented an elevated efflux into both compartments but occurred mainly (72%) via the body rather than the head region. This second peak was accompanied by a substantial increase in [14C]-acetamide clearance but only a modest further rise in [14C]-thiourea clearance. The acetamide to thiourea permeability ratio was typical of UT-A type transporters in other fish. [3H]-PEG-4000 clearance was stable at this time at about double the terrestrial rate, and excretion rates of urea and its analogs were many fold greater than could be accounted for by [3H]-PEG-4000 clearance. We conclude that the first peak may be explained by elevated urinary excretion and paracellular diffusion across the gills upon resubmergence, while the second peak is attributable to a delayed and prolonged activation of a UT-A type facilitated diffusion mechanism, primarily in the skin and perhaps also in branchial epithelia.

Ammonia↗
PubMed2005

Genetic and dietary factors in urinary citrate excretion.

BACKGROUND AND PURPOSE: Hypocitraturia, an important risk factor for calcium oxalate nephrolithiasis, is the result of numerous factors. We studied citrate excretion by patients with and without stones consuming normal and controlled formula diets. SUBJECTS AND METHODS: Subjects with and without a history of calcium oxalate stones (N = 101 per group) provided two or three 24-hour urine specimens during consumption of self-selected diets. Data also were collected on subsets of subjects consuming formula (Ensure) diets. Citrate was determined using the citrate lyase method of Petrarulo and associates, and values for multiple specimens were averaged. The data were adjusted for creatinine excretion and examined on a per-day basis. RESULTS: The mean citrate excretion of the non-stone formers was slightly but not significantly higher than that of the stone formers (442 +/- 217 versus 378 +/- 153 mg/g of creatinine). All statistical analyses revealed highly significant differences between, but not within, individuals, a result compatible with a genetic influence. In the normal population, 5% of subjects had a citrate excretion <200 mg/g of creatinine, whereas this result was seen in 34% of the stone-forming subjects. When the subjects consumed a formula diet, women in both groups had much higher citrate excretion than when on a self-selected diet, but little difference was seen in the men. The patterns of citrate recovery suggest low, intermediate, and high excretors. In the normal population, 15% of subjects excreted <340 mg/g of creatinine, whereas this was true of 43% of the stone-forming subjects. Analysis of six families suggested three excretor phenotypes, with a codominant pattern of inheritance. CONCLUSION: These findings imply a genetic influence on citrate excretion, as has already been demonstrated for calcium excretion. Further studies of genetic influences on calcium oxalate stone formation are warranted.

Adult↗
PubMed2005

Iodine nutrition, nodular thyroid disease, and urinary iodine excretion in a German university study population.

We determined the influence of different nutritional factors on the urinary iodine excretion in an East German university population. First, we assessed iodine excretion in spot urine samples. Second, we measured iodine content in the university canteen meals, where approximately 20% of the probands had regular meals. Third, we used a special food questionnaire to assess for other sources of nutritional iodine intake, namely iodine tablets, fish consumption, etc. Fourth, we determined the actual prevalence of goiter and thyroid nodules in our probands by high-resolution ultrasonography. The mean urinary iodine excretion in our cohort was 109 +/- 81 microg/g level indicating a borderline adequate iodine intake (100-200). The frequency of thyroid nodules was 30% and the frequency of goiter 11%. Thyroid volumes greater than 18 mL and 25 mL were considered to be enlarged in adult women and men respectively. Urinary iodine excretion was not related to the presence of goiter or thyroid nodules. In addition urinary iodine excretion did not vary with regular consumption of canteen meals, which contained approximately 50% of the daily recommended iodine intake. In contrast probands with regular supplementary intake of iodine tablets had significantly higher values of urinary iodine excretion (169 +/- 130 microg/g) compared to participants without (103 +/- 87 microg/g). No other single nutritional factor (e.g., salt, milk, or bread) had a statistically significant impact on urinary iodine excretion or was able to raise the urinary iodine excretion above the level of marginal iodine deficiency. In summary, the nutritional iodine intake in a Saxonian study population was found to be close to the margin of iodine deficiency. This shows insufficient supplementation of iodine through iodized salt/industrialized food production.

Adult↗
PubMed1996

Utility of creatinine excretion in body-composition studies of healthy men and women older than 60 y.

This study evaluated whether aging alters the usefulness of creatinine excretion as an index of lean body mass (LBM) or muscle mass in healthy men and women. Creatinine excretion was determined while 24 young (15 men and 9 women aged < 32 y) and 38 older (23 men and 15 women aged > 60 y) healthy volunteers stayed at a clinical research center for 3 d. Total LBM was determined by 40K counting in all subjects, and cross-sectional areas of upper arm and thigh muscles were determined in some subjects (10 young, 20 old) by magnetic resonance imaging. The slopes and intercepts of the regression equations relating LBM to average daily creatinine excretion were the same in the younger and older groups, and the precision with which LBM could be determined from creatinine excretion was not diminished by aging. Creatinine excretion was closely correlated with cross-sectional areas of upper arm (r = 0.85) and thigh (r = 0.88) muscles, and the slopes and intercepts of the regression equations were not significantly affected by age. The older group had a mean LBM smaller than that of the younger group, which was accounted for entirely by a smaller muscle mass. Mean resting metabolic rate (RMR), whole-body protein turnover rate, and thigh strength were lower in the older group than in the young group. Adjustment of RMR and protein turnover for creatinine excretion or LBM eliminated the age effects. Strength was lower in the older group even after adjustment for creatinine excretion or LBM. This study indicates that creatinine excretion is useful for evaluating body composition in both young and old subjects.

Adult↗
PubMed1997

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.

Adult↗
PubMed1998

Influence of soybean processing, habitual diet, and soy dose on urinary isoflavonoid excretion.

In an attempt to explain the wide individual variation seen in urinary isoflavonoid phytoestrogen excretion, we conducted a series of 3 human feeding studies: a large cross-sectional study of equol production in humans with a soy challenge, a comparison of phytoestrogen metabolism when subjects consumed fermented and unfermented soy products, and a dose-response study of urinary isoflavonoid excretion at the low end of soy consumption. All studies were conducted in young, healthy humans. Urinary isoflavonoids were measured by isotope-dilution gas chromatography-mass spectrometry. Similar to results from other studies, 35% of screened subjects (30 men and 30 women) excreted equol (>2000 nmol/d). In women, equol excretion was associated with higher intake of dietary fiber and carbohydrate. Fermentation of soy decreased the isoflavone content of the product fed but increased the urinary isoflavonoid recovery, suggesting that fermentation increases availability of isoflavones in soy. When soy-protein powder was fed at 0, 5, 10, and 20 g/d (0-36 mg isoflavones), there was a linear dose response of urinary isoflavonoid excretion to soy consumption that did not differ between subjects with high and low equol excretion. These results suggest that equol excretion may be related to the fermentable carbohydrate content of the diet; additional study is needed. Processing of soy affects isoflavone metabolism and must be considered in recommending exposure to isoflavones from soyfoods. Although optimal isoflavone exposure for disease protection has not been determined, urinary isoflavonoid excretion appears linear at low-to-moderate soy consumption.

Biological Availability↗
PubMed2002

Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research.

BACKGROUND: Urinary creatinine reference values that take anthropometric data into account, which is mandatory during growth, are not available for healthy white children. OBJECTIVE: We sought to establish anthropometry-based reference values for 24-h urinary creatinine excretion in healthy white children aged 3-18 y. DESIGN: Anthropometric variables and 24-h urinary creatinine excretion rates were determined cross-sectionally (225 boys and 229 girls). Age and sex dependency of 24-h creatinine excretion (crude and related to individual anthropometric variables) were assessed to derive appropriate creatinine reference values. The applicability of these creatinine reference values for estimation of daily excretion of certain analytes was assessed in 40 additional children. RESULTS: Sex-specific, body-weight-related creatinine reference values were derived for the following age groups: 3, 4-5, 6-8, 9-13, and 14-18 y. The 5th percentile exceeded 0.1 mmol x kg(-1) x d(-1) in all age groups >3 y. The use of these creatinine reference values for estimating average 24-h excretion rates of certain analytes (determined as the ratio of analyte to creatinine in spot urine samples) yielded reasonable estimates of mean 24-h urinary excretion rates actually analyzed (spot and 24-h urine samples from the same children). Ideal 24-h creatinine excretion values for height were also derived for a potential determination of the creatinine height index. CONCLUSIONS: Established anthropometry-based creatinine reference values are recommended as a convenient, simple tool to 1) identify severe 24-h urine collection errors, 2) calculate average 24-h excretion rates of certain analytes (from respective ratios of analyte to creatinine) determined in spot urine samples, and 3) assess somatic protein status by determining the creatinine height index.

Adolescent↗
PubMed2003

Correlates of urinary albumin excretion in young adult blacks and whites: the Coronary Artery Risk Development in Young Adults Study.

The rate of urinary albumin excretion is an important risk factor for kidney failure, stroke, and cardiovascular disease, perhaps because higher albumin excretion reflects endothelial cell dysfunction. The authors characterized urinary albumin excretion according to blood pressure, diabetes mellitus, and other factors in 2,582 Black and White participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study who were aged 18-30 years in 1985-1986. Urinary albumin and creatinine concentrations were determined using single untimed samples 10 and 15 years later. The albumin:creatinine ratio was analyzed as a continuous variable and a dichotomous variable (higher albumin excretion, including microalbuminuria (25-249 mg/g) and macroalbuminuria (>or=250 mg/g)). Seventy percent of persons with increased albumin excretion were both normoglycemic and normotensive (systolic/diastolic blood pressure <140/90 mmHg and no use of antihypertensive drugs). Even when diabetic subjects, who have greater risk, were excluded, albumin excretion rose continuously as blood pressure increased among Blacks; increases started at systolic/diastolic blood pressures of 130/85 mmHg among Whites. Furthermore, blood pressure measured up to 15 years earlier predicted incident higher albumin excretion at year 15. These findings persisted after adjustment for age, body mass index, smoking, and blood lipid and plasma insulin levels. A risk of higher urinary albumin excretion exists at blood pressure levels below those commonly regarded as hypertension, with a greater risk among Blacks than among Whites.

Adolescent↗
PubMedDate not supplied

A review of human salmonellosis: II. Duration of excretion following infection with nontyphi Salmonella.

Convalescent excretion is a common sequel to salmonella infection, but in contrast to infections with Salmonella typhi, no clear picture of the natural history of nontyphi Salmonella excretion has emerged. The literature concerning frequency and site of chronic carriage, patterns of excretion, and relationship to bacteriologic methods used for enumeration of organisms was reviewed. An examination of 32 studies including 2,814 patients who were observed after salmonella infection showed that median duration of excretion was approximately five weeks. In univariant analyses, excretion was more prolonged in children less than five years of age, persons with symptomatic infections, persons infected with serotypes other than Salmonella typhimurium, and persons studied after first onset of symptoms. Persistent excretion beyond one year occurred in fewer than 1% of subjects. Despite the large number of convalescent excretors in the community at any one time, the paucity of outbreaks in which such food handlers or hospital personnel are implicated suggests that their role in transmission of salmonella infection is small. Because convalescent excretion is so common and persistent excretion and transmission so uncommon, follow-up fecal cultures after salmonella infections are rarely necessary.

Adolescent↗
PubMed1990

Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia.

Cytomegalovirus (CMV) viremia and excretion from the oropharynx and urine were examined for their utility in predicting the development of CMV disease, including pneumonia and gastrointestinal disease, among 617 marrow allograft recipients. CMV viremia had a 60% and excretion from oropharynx or urine or viremia a 44% positive predictive value for the development of CMV disease. Viremia or excretion preceded disease onset by a median of 15 days among those in whom excretion occurred first. In stepwise time-dependent proportional hazards regression analyses, CMV viremia and positive serology before transplant were predictive for both CMV pneumonia and gastrointestinal disease. Oropharyngeal excretion was independently predictive for gastrointestinal disease but not pneumonia. Urinary excretion was not independently predictive. Acute graft-versus-host disease was predictive for pneumonia but not gastrointestinal disease. Thus use of CMV excretion, particularly viremia, as a marker to determine the initiation of antiviral chemotherapy could be effective in preventing progression of infection to serious disease. However, with standard virologic techniques this strategy would not be effective in patients (32% in this study) without CMV excretion detected before the onset of pneumonia or gastrointestinal disease.

Adolescent↗
PubMed1990

Urinary orotic acid excretion in sheep: effects of nitrogen, glucose and arginine.

The urinary excretion of orotic acid was investigated in four sheep. Nitrogen and energy intake were varied by infusions of urea and glucose. The effect of arginine infusion was also investigated. Nitrogen intake of 10.4 g/d led to a urinary excretion of orotic acid of 357 +/- 61 micrograms/d. Increasing N intake to 21.4 g/d significantly increased urinary orotic acid excretion to 747 +/- 46 micrograms/d. Glucose infusion (300 g/d) significantly decreased orotic acid excretion when N intake was 10.4 g/d, whereas arginine infusion (2.3 g/d) did not alter the excretion of orotic acid under these conditions. When arginine was infused at higher N intake (21.4 g/d), orotic acid excretion decreased from 822 +/- 74 to 624 +/- 46 micrograms/d. It is concluded that increasing N intake is accompanied by an enhanced urinary excretion of orotic acid. This excretion of orotic acid is significantly modified by glucose or arginine.

Abomasum↗
PubMed1991

Brewer's spent grain, serum lipids and fecal sterol excretion in human subjects with ileostomies.

A crossover design studying lipid and apoprotein levels in serum and excretion of sterol, nitrogen and fat in ileostomy effluent was performed in 10 subjects fed diets with or without supplementation with brewer's spent grain, which is the residue of barley after the brewing of beer. More cholesterol, nitrogen, fat and energy were excreted in the ileostomy effluents when the subjects consumed a brewer's spent grain supplemented, high fiber diet than when they consumed a low fiber diet. No significant change was found in the daily net sterol excretion. The six subjects with low daily excretion of bile acids (less than 1000 mg/24 h) had increased cholesterol and net cholesterol and decreased bile acid excretion per day, and lowered serum LDL-cholesterol and apoprotein B levels after supplementation with brewer's spent grain. We propose that subjects with low daily bile acid excretion are suitable models for studying the effect of dietary changes on sterol excretion and serum lipid levels. Increased fecal cholesterol excretion is suggested to be the primary mechanism for the serum LDL-cholesterol lowering effect of brewer's spent grain.

Adult↗
PubMed1998

Effects of low-dose nifedipine on urinary protein excretion rate in patients with renal disease.

BACKGROUND: The observation that proteinuria is an important determinant of the progression of renal disease has prompted numerous studies on the effects of antihypertensive agents on protein excretion. Reports on the proteinuric effects of calcium-channel blockers are quite controversial. It has been suggested that the short-acting dihydropyridine calcium-channel blocker nifedipine increases protein excretion by interference with tubular protein reabsorption. METHODS: In a randomized controlled trial 10 patients with renal disease and proteinuria were treated with a dose of 10 mg nifedipine o.d. (slow release formulation) for 1 week. The acute effects on renal and systemic haemodynamics and on urinary albumin, IgG, and beta2-microglobulin excretion were investigated during a clearance study in the supine position after the first dose. After 1 week of treatment urinary protein excretion rates were measured in 24-h urine samples collected in the ambulatory patient in consecutive fractions of 4-8 h during normal daily activities. RESULTS: After the first dose nifedipine lowered mean arterial blood pressure in the supine position by 7+/-1 mmHg (<0.01), attenuated proximal tubular sodium reabsorption (fractional excretion of sodium 3.48+/-0.49 vs 2.62+/-0.35% during control, P<0.02), but did not affect proximal tubular protein reabsorption (fractional urinary excretion of beta2-microglobulin 0.97+/-0.30 vs 0.98+/-0.32% during control, NS). The decrease in blood pressure was not accompanied by decreases in urinary albumin or IgG excretion rates. The selectivity index as well as GFR, RPF, and FF did not change. Continued treatment for 1 week with nifedipine did not influence 24-h protein excretion. However, we observed a rise of proteinuria during daily activities in the first 4 h after drug intake compared to the start of the study with the patients in supine position. During control measurements there was a slight increase in proteinuria. During nifedipine the increase in proteinuria was more marked and correlated with the selectivity index. CONCLUSIONS: (1) Nifedipine 10 mg orally did not impair tubular protein reabsorption. (2) Nifedipine had no immediate antiproteinuric effect despite the observed blood pressure reduction. (3) Nifedipine increased proteinuria in ambulatory urine collections. This latter observation might explain the seemingly different effects of dihydropyridine calcium-channel blockers as reported in previous studies.

Adult↗
PubMed2000

Determinants of urinary excretion of Tamm-Horsfall protein in non-selected kidney stone formers and healthy subjects.

BACKGROUND: The aim of the study was to measure urinary excretion of Tamm-Horsfall protein (THP), an important inhibitor of crystallization, and to identify possible determinants of urinary THP excretion in non-selected kidney stone formers (SF) and healthy subjects (C). METHODS: By means of a commercially available ELISA (Pharmacia and Upjohn/Elias, Germany), we measured THP in 24-h urines of 104 SF (74 males/30 females, age 16-74 years) who had formed 8.7+/-2.4 stones (range 1-240), and of 71 C (41 males/30 females, age 22-62 years). Types of stones formed by SF were 88 calcium, eight uric acid, six infection, and two cystine. All values are means+/-SE. RESULTS: The normal range (5th to 95th percentile) of U(THP)xV was 9.3-35.0 mg/day in males and 9.0-36.3 mg/day in females respectively. Mean U(THP)xV was 21.3+/-1.2 mg/day (range 3. 4-51.6) in male and 15.2+/-1.6 mg/day (range 1.8-32.3) in female SF (P=0.008 vs male SF). Since U(THP)xV was positively correlated with C(Crea) (r=0.312, P=0.001) in SF as well as with U(Crea)xV (r=0.346, P=0.0001) and with body surface (r=0.271, P=0.0003) in all study subjects, mean THP/Crea (mg/mmol) was used for all further calculations. Overall, THP/Crea was lower in SF (1.42+/-0.07 vs 1. 68+/-0.08, P:=0.015), mainly due to increased THP/Crea in female C (2.08+/-0.11, P=0.0036 vs female SF, P=0.0001 vs male C and vs male calcium SF), which also explains decreased THP/Crea values in calcium SF (1.46+/-0.08, P=0.041 vs C). In addition, THP/Crea was reduced in uric acid SF (1.11+/-0.21, P=0.049 vs C). Whereas THP/Crea was not related to age, urine volume, intake of dairy calcium, or urinary markers of protein intake, either in C or in SF, it correlated significantly with urinary Citrate/Crea, both in C (r=0.523, P=0.0001) and in SF (r=0.221, P=0.025). In C only, but not in SF, THP/Crea was correlated with urinary Calcium/Crea (r=0. 572, P=0.0001) and with Oxalate/Crea (r=0.274, P=0.022). CONCLUSIONS: Both in C and SF, urinary THP excretion is related to body size, renal function and urinary citrate excretion, whereas dietary habits apparently do not affect THP excretion. Uric acid and calcium stone formation predict reduced THP excretion in comparison with C, whereas female gender goes along with increased urinary THP excretion in C. Possibly most relevant to kidney stone formation is the fact that THP excretion rises only in C in response to increasing urinary calcium and oxalate concentrations, whereas this self-protective mechanism appears to be missing in SF.

Adult↗
PubMed1981

Stringent control of intermediary metabolism in Escherichia coli: pyruvate excretion by cells grown on succinate.

A large amount of pyruvate was excreted into the medium by CP78 (rel+) cells grown on succinate when they were starved for amino acids. In contrast, no such excretion was observed with CP79 (rel-) cells. This phenomenon was also seen with two other isogenic pairs of strains: NF161 (rel+) and NF162 (rel-), and 10B601 (rel+) and 10B602 (rel-). Besides succinate, L-malate, and fumarate were effective carbon sources for the excretion, but glucose, glycerol, and acetate were not. When DL-lactate was used, not only CP78 but also CP79 cells excreted pyruvate. Experiments using [1,4-14C]succinate as a carbon source revealed that pyruvate was formed by decarboxylation of one carboxyl group of succinate and that the pyruvate excretion amounted to about 40% of the total succinate degraded. Experiments designed to elucidate the mechanism of the excretion yielded the following observations. (i) The concentration of pyruvate in CP78 cells grown on the C4-dicarboxylic acids mentioned above was not significantly changed upon amino acid starvation. (ii) Guanosine 5'-diphosphate-3'-diphosphate exerted no effect on the activities of several enzymes thought to be involved in pyruvate-related metabolism. It is suggested firstly that the excretion was not due to some impairment in the biosynthetic pathway of a particular amino acid, but was due to the stringent control of central amphibolic metabolism, and secondly that no de novo protein synthesis was involved in the excretion.

Amino Acids↗
PubMed1985

Relationship between sleep efficiency and urinary excretion of catecholamines in bed-rested humans.

The relationship between urinary excretion of catecholamines during sleep and sleep disturbance was examined in four healthy subjects who were confined to bed for approximately 1 week under an entrained condition. Polysomnographic recordings were made throughout the period of continuous bed rest. Free epinephrine and norepinephrine excretion were measured. Sleep efficiency, i.e., percentage of total sleep time over an allotted sleep period, was an indicator of sleep disturbance. All subjects showed a negative correlation between sleep efficiency and epinephrine excretion (average correlation coefficient -0.79, p less than 0.004). Norepinephrine excretion correlated negatively with sleep efficiency in only one subject, and the group average correlation coefficient of -0.28 was not significant. Circadian variations were observed in sleep efficiency and catecholamine excretion. Although epinephrine excretion was influenced by psychophysiological stress arising from the experimental conditions of forced bed rest, the correlation between sleep efficiency and epinephrine excretion remained stable and negative. The urinary excretion of epinephrine could be an effective indicator of sleep disturbance.

Adult↗
PubMed2000

Succimer and the urinary excretion of essential elements in a primate model of childhood lead exposure.

Succimer is considered to be a safe and effective treatment for lead (Pb) poisoning, since it reduces body Pb levels without an apparent diuresis of other essential elements. However, while existing clinical data indicate that succimer does not significantly increase the excretion of non-target elements, those studies have also reported a wide range of outcomes. Therefore, we investigated whether succimer treatment measurably increased the urinary excretion of essential elements in a primate model of childhood Pb exposure. Infant rhesus monkeys (Macaca mulatta) were exposed to Pb from birth through one year of age, and presented blood Pb levels of approximately 40-50 microg/dL at the start of treatment. Subsequently, they were treated with succimer (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days, n = 15) or vehicle (n = 14) for 19 days. Complete urine samples were collected over the first 5 days of treatment, and were analyzed for levels of calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), nickel (Ni), and zinc (Zn), using trace metal-clean techniques and magnetic sector-ICP-MS. Succimer treatment significantly (p < 0.05) reduced blood Pb levels when compared to the vehicle group over the treatment period, and concomitantly produced a significant >4-fold increase in urinary Pb excretion. Succimer treatment also significantly (p < 0.05, multivariate ANOVA) increased the urinary excretion of essential elements, but only when the cumulative total excretion over treatment days 1-5 for all elements were considered. None of these relative increases reached statistical significance for any particular element x day, although increases in Zn (day 3) excretion were only marginally non-significant (0.1 > p > 0.05). Multivariate analyses of a subset of elements (Cu, Fe, Mn, Zn) similarly indicated no significant effect of succimer treatment overall, although the urinary excretion of Mn was significantly increased on day 3 of treatment. Collectively, these data indicate that succimer does contribute to an increase in the urinary excretion of essential elements, although not significantly for any single element considered here. This may be important in Pb-exposed children, who can possess reduced trace element reserves due to nutritional deficiencies.

Animals↗
PubMed1997

Urinary pyridinium cross-link excretion is increased in critically ill surgical patients.

OBJECTIVES: To determine: a) the rate of pyridinium cross-links of collagen excretion, breakdown products of bone, in critically ill surgical patients in the intensive care unit (ICU); and b) the relationship between cross-link excretion and nitrogen excretion and balance to ascertain whether collagen breakdown products contribute to protein losses during a hypercatabolic state. DESIGN: Observational study starting on the first postoperative day to 20 days or until discharge. SETTING: A surgical ICU in a University hospital. PATIENTS: Nine mechanically ventilated, postoperative surgical patients (73 +/- 3 [SD] yrs), receiving routine parenteral nutrition (18% protein) and 17 age-matched healthy subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Resting energy expenditure was determined daily for < or = 5 days after admission, and energy intake was set at 1.04 times the initial energy expenditure; thereafter, values of intake were reset weekly. Daily 24-hr urine samples were analyzed for cross-links, total and urea nitrogen, calcium, and creatinine for 20 days or until discharge. Two urine samples were also analyzed for cross-links in the healthy subjects. The excretion of cross-links from the surgical patients was markedly higher (p < .001) than in the healthy subjects, and calcium balance was significantly negative (p < .05). Patients who were discharged from the ICU within 5 days showed a lower rate of cross-link excretion (p < .02) and less day-to-day variability, compared with those patients who stayed longer, whether calculated over the course of the study or over the first 2 days in the ICU. There was no correlation between cross-links and energy expenditure, nitrogen excretion, or balance. CONCLUSIONS: The rate of cross-link excretion in critically ill patients: a) is markedly increased; b) is greater within the first two postoperative days in those patients who have an extended stay (> 5 days) in the ICU; and c) is independent of the rate of nitrogen excretion. These findings suggest that critically ill postoperative patients experience an acute breakdown of collagen, which is likely due to resorption of bone or possibly comes from other collagen sources.

Aged↗