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PubMed1988

Relation between renal and hepatic excretion of drugs: IX. Acceleration of phenol red excretion via kidney and liver in rats of different ages by dexamethasone treatment.

Experiments were performed on 10-, 20-, and 55-day-old female rats. After treatment with dexamethasone (60 or 80 micrograms/100 g b.wt. for 3 days, once daily) there is a significant increase in renal phenol red excretion only in 10-day-old rats. In contrast, the stimulatory effect of dexamethasone treatment on the hepatic excretion of this dye occurs exclusively in mature, 55-day-old rats. After repeated administration of this hormone in nephrectomized rats there is an increase of hepatic phenol red excretion, and maximal transport capacity increases from 6-8 to 12 mg/100g b.wt. X hour. In renal cortical slices there is no significant influence of dexamethasone on phenol red accumulation in vitro, whereas accumulation of the dye in liver tissue seems to be diminished. In rats of all groups kidney and liver weights increased significantly after dexamethasone treatment. Calculation of total accumulation capacity (= accumulation per 1 g X organ wet weight) also results in unchanged accumulation capacity in the kidney, but transported phenol red amounts in the liver are distinctly diminished. This is in contrast to the in vivo findings. Possible reasons are discussed.

Aging↗
PubMed1987

Relation between renal and hepatic excretion of drugs. VI. Influence of pretreatment with phenol red on renal excretion and accumulation capacity of kidney or liver slices of immature and adult rats.

Pretreatment with phenol red causes a significant increase in renal excretion of p-amino-hippurate (PAH) in adult rats. In vitro experiments have shown that phenol red pretreatment significantly enhances the accumulation of PAH in renal tubular cells of adult rats. Thus the stimulation of active renal tubular PAH transport is at least in part responsible for its accelerated excretion via urine. A similar phenol red administration does not enhance the renal excretion of this dye, neither in adult nor in immature rats. In accordance with these in vivo findings the renal accumulation of phenol red is not increased after pretreatment with this dye. Remarkably the repeated administration of phenol red causes a distinct reduction of phenol red accumulation capacity in liver tissue. The rate of accumulation of both PAH and phenol red in renal cortical slices increases significantly during maturation; in liver tissue slices such an intensification does not occur. Under anaerobic conditions an active energy requiring uptake of phenol red does not take place and an accumulation by active transport of the dye can also be excluded. Therefore a passive uptake of phenol red and a binding of the dye in renal tubular cells could explain the distinct accumulation of phenol red in tissue slices from the kidney under nitrogen atmosphere. In 55-day-old rats the anaerobic phenol red accumulation in the liver is diminished after pretreatment with this dye.

Aging↗
PubMed1977

[The follow-up of high risk pregnancies with the determination of estriol 16-glucuronid excretion. Second: Excretion in preeclampsia, post maturity, intrauterine growth retardation, diabetes, Rh incompatability and intrauterine fetal deaths (author's transl)].

The estriol 16-glucuronid excretion was determined in 186 urine samples in cases with preeclampsia, post maturity, pregnancies past the expected date of confinement, intra-uterine fetal deaths, congenital anomalies, Rhesus incompatability and diabetes mellitus. In groups with mild dystrophy, severe dystrophy, and intra-uterine fetal death, three zones of estriol 16-glucuronid excretion were determined. Zone 1 is suggestive of a possible fetal impairment. Zone 2 shows a high probability of fetal impairment and Zone 3 was considered as lethal zone suggestive of imminent intra-uterine fetal death. The degree of rhesus incompatability, disease of the fetus or of diabetogenic fetopathy was not recognizable by the estriol 16-glucuronid excretion.

Abnormalities, Multiple↗
PubMed1985

[Effects of a new vasodilator, budralazine on water drinking activity, plasma norepinephrine, plasma angiotensin II, plasma arginine vasopressin, plasma serotonin concentration, urinary aldosterone excretion rate and urinary catecholamine excretion rate in rats].

Present study was undertaken to elucidate the effects of a new vasodilatating antihypertensive drug, budralazine on water drinking behavior and humoral factors including plasma norepinephrine (NE), angiotensin II (A II), arginine vasopressin (AVP), serotonin (5-HT) concentrations, urinary aldosterone and catecholamine excretion rates. After oral budralazine administration (10 mg/kg/day, p.o., for 7 days), systolic tail blood pressure of Wistar Kyoto rats (WKY) decreased significantly. While, heart rate and water drinking activity of WKY significantly increased. Urinary catecholamine excretion rate did not change after oral administration of budralazine (10 mg/kg and 100 mg/kg/day, p.o.; for 7 days). However, significant increase in urinary aldosterone excretion rate was demonstrated. Both plasma A II and NE concentrations tended to increase after oral administration of budralazine (100 mg/kg/day). Plasma AVP and 5-HT concentrations were not influenced by budralazine. These findings suggest that budralazine acts on renin angiotensin aldosterone system as compared to that in the sympathetic nervous system.

Aldosterone↗
PubMed1973

Virus excretion in smallpox. 1. Excretion in the throat, urine, and conjunctiva of patients.

Excretion of virus in the throat, urine, and conjunctiva of smallpox patients was studied daily for 2-3 weeks after the onset of fever. The virus titre in the throat and urine of haemorrhagic and confluent cases was higher than in discrete cases. The duration of virus excretion was also greater in confluent cases than in discrete cases. Conjunctival swabs from all 12 smallpox patients with conjunctivitis were positive for virus. The duration and titre of virus excretion in the throat, urine, and conjunctiva of patients were not related to their age or sex and did not depend on whether or not they had received a primary vaccination.

Adolescent↗
PubMed1979

Pulmonary excretion of carbon monoxide in the human newborn infant as an index of bilirubin production: III. Measurement of pulmonary excretion of carbon monoxide after the first postnatal week in premature infants.

Using a single pass, flow-through system, the excretion rate of endogenously produced carbon monoxide (VeCO) was measured as an index of bilirubin production in 41 Caucasian infants of various gestational ages after the first postnatal week. twenty-one were less than or equal to 32 weeks gestation. The mean slope for the 25 premature infants with multiple VeCO determinations was -0.21 +/- 0.11 (SE) microliters/kg/hour per day (P less than .025, one-tailed). Fifteen premature infants with at least three VeCO determinations during the first 30 days of life had an average decrease in total CO excreted of 1.33% per day compared to the extrapolated initial value of total CO excretion of 27.0 +/- 2.0 (SE) microliters/hour, giving a calculated maximum red cell life span of 75 days.

Bilirubin↗
PubMed1980

[Studies on the absorption, excretion and distribution of aclacinomycin A: absorption, excretion and distribution of aclacinomycin A in mice, rabbits and dogs by photometric assay (author's transl)].

An anthracycline antitumor antibiotic, aclacinomycin A, was given to mice, rabbits or dogs intravenously to study the pharmacokinetics by photometric assay based on the absorption of anthracycline ring. The drug was rapidly eliminated from the blood in these animals. Drug levels were much higher in the blood cells than in the plasma. Tissue levels in dogs were 50 approximately 100 times higher than the blood levels, which showed the drug was rapidly transferred from the blood to tissues after administration. Higher levels were observed in the lungs, spleen and lymph nodes, where the drug was present as aclacinomycin A itself and the glycoside-type metabolites that were biologically active. The active form was also detected in the pancreas, heart, thymus, bone marrow and gastrointestinal tract. In the liver and kidneys, biologically inactive aglycone-type metabolites were observed. About 2 approximately 4% of the drug given to rabbits or dogs was recovered in the urine by 72 hours after administration, in which only 10% of the excreted drug was active form in rabbits but about 65% in dogs. The rest was inactive aglycone-type metabolites that were excreted almost in the conjugated form. Biliary excretion also contributed to the total clearance of the drug. Aclacinomycin A was absorbed even by oral administration in rabbits and dogs. Tissue distribution of the drug orally given to dogs was similar to that in intravenous administration, except that higher levels of active form were detected in the gastrointestinal tract and of inactive form in the liver.

Absorption↗
PubMed1981

[Studies on absorption and excretion of cefmetazole in neonates and excretion into the bile of infants with congenital biliary atresia (author's transl)].

This is studies concerning the absorption and excretion of cefmetazole in neonates and the excretion into the bile of infants with congenital biliary atresia. 1. The concentration of cefmetazole was measured in the serum and urine of 2 neonates at the postoperative period. 2. The concentration measured in the serum showed a level similar to those of cases in pediatrics at other institutes regardless of the operation. 3. The recovery value of cefmetazole in the urine of the neonate is not different from those of other institutes even if it is a postoperative case, provided that the urine quantity is maintained. 4. Excretion of cefmetazole into the urine and bile was measured in 2 cases of congenital biliary atresia after the biliary diversion. 5. The concentration of cefmetazole in the bile of infants with congenital biliary atresia is lower than those of adults. It follows that the recovery percentage in the bile is low but the converse was true in the urine recovery. This seemed to be due to liver dysfunction that are characteristic in congenital biliary atresia. However, the concentration of cefmetazole in the bile was sufficient to obtain effective therapeutic level.

Anti-Bacterial Agents↗
PubMed1992

Metabolism of boldenone in man: gas chromatographic/mass spectrometric identification of urinary excreted metabolites and determination of excretion rates.

Urinary metabolites of boldenone (androsta-1,4-dien-17 beta-ol-3-one) following oral administration of boldenone (doses from 11 to 80 mg) to man were isolated from urine via XAD-2 adsorption and enzymatic hydrolysis with beta-glucuronidase from Escherichia coli. The isolated metabolites were derivatized with N-methyl-N-trimethylsilyltri- fluoroacetamide/trimethyliodosilane and analysed by gas chromatography/mass spectrometry with electron impact (EI) ionization at 70 eV. Boldenone (I) and four metabolites were identified after hydrolysis of the urine with beta-glucuronidase: 5 beta-androst-1-en-17 beta-ol-3-one (II), 5 beta-androst-1-ene-3 alpha, 17 beta-diol (III), 5 beta-androst-1-en-3 alpha-ol-17-one (IV) and 5 beta-androst-1-en-6 beta-ol-3,17-dione (V). Five further metabolites in low concentration were identified without enzymatic hydrolysis after treatment of the urine with potassium carbonate: 5 beta-androst-1-ene-3,17-dione (VI), 5 alpha-androst-1-ene-3,17-dione (VII), androsta-1,4-diene-3,17-dione (VIII), androsta-1,4-diene-6 beta,17 beta-diol-3-one (IX) and androsta-1,4-dien-6 beta-ol-3,17-dione (X). The identification of the metabolites is based on the gas chromatography retention index, high-performance liquid chromatography retention, EI mass spectrum, chemical reactions of the isolated metabolites, and synthesis of metabolites II, III, IV, VI and VII. The EI mass spectra of the bis-trimethylsilyl derivatives of boldenone and its metabolites display all intense molecular ions, M-15 ions and fragment ions originating from cleavage of the B-ring. The excreted metabolites can be separated in basic extractable labile conjugates and in stable conjugates. More than 95% of metabolites are excreted as stable conjugates.

Chromatography, High Pressure Liquid↗
PubMed1982

[Investigations on the correlation between vinyl chloride (VCM)-uptake and excretion of its metabolites by 15 VCM-exposed workers. II. Measurements of the urinary excretion of the vcm-metabolite thiodiglycolic acid ].

Fifteen workers employed in a PVC producing plant were investigated concerning their individual vinyl chloride (VCM) exposure and the urinary excretion of the VCM metabolite thiodiglycolic acid (TdGA). The urine concentrations found were in the range 0.94-20.4 microgram/ml. These could be compared with exposure data calculated from VCM air analyses performed by personal air sampling and corrected with respect to the exposure times of the workers. The amounts of TdGA excreted within 24 h were correlated with the effective VCM body concentrations calculated from the exposure data as mean values for 12 h periods (Spearman coefficient P=alpha less than 0.005). This correlation resembles a function of the Michaelis-Menten type. It could be shown that during short exposure periods of less than 5 min, the metabolite formation in relation to the exposure data was lower than during longer periods of exposure although, as would be expected, there were some fluctuations of the exposure level. Therefore, the VCM body concentrations could not normally reach steady state values.

Environmental Exposure↗
PubMed1992

Formic acid excretion in comparison with methanol excretion in urine of workers occupationally exposed to methanol.

A semiautomated head-space gas chromatographic (GC) method was developed for measuring formic acid in urine. The method consists of heating 1 ml urine sample in a 20-ml air-tight vial in the presence of 1 ml sulfuric acid and 2 ml ethanol at 60 degrees C for 30 min for ethyl esterification and air-liquid equilibrium, followed by automatic injection of 1 ml head-space air into a flame ionization detector GC. The detection limit was 1 mg/l for formic acid. The method was applied to measure formic acid in the shift-end urine samples from 88 workers exposed to methanol at 66.6 ppm (as geometric mean) and in urine samples from 149 nonexposed controls. Methanol concentrations were also determined. Regression analysis showed that urinary formic acid concentrations, as observed or corrected for either creatinine concentration or specific gravity of urine (1.016), correlated significantly with time-weighted average intensities of exposure to methanol vapor. Men excreted significantly more formic acid than women. Comparison with methanol excretion suggested, however, that urinary formic acid is less sensitive than urinary methanol as an indicator of methanol vapor exposure, primarily because the background level for formic acid (26 mg/l as arithmetic mean, or 23 mg/l as geometric mean) is more than ten times higher than the level for methanol (1.9 mg/l as arithmetic mean, or 1.7 mg/l as geometric mean). After theoretical methanol exposure at infinite concentration, the urinary formic acid/methanol ratio should be about 0.4.

Adult↗
PubMed1977

Proline excretion in Escherichia coli: a comparison of an argD+ strain and a proline-excreting argD- derivative.

In an attempt to deduce the physiological basis of proline excretion in argD- strains of Escherichia coli K12, several properties of an argD+ (nonexcreting) and an argD- (excreting) derivative were compared. No difference was found in the transport or in the utilization of either proline or its immediate precursor, delta1-pyrroline-5-carboxylate (PCA). Furthermore, no differences were found in the physical or kinetic properties of partially purified preparations of the enzyme mediating the final step in proline biosynthesis, PCA reductase. The specific activity of PCA reductase was, however, consistently higher in crude extracts prepared from the argD- mutant.

Amidohydrolases↗
PubMed2005

Predicting total urinary nitrogen excretion from urinary urea nitrogen excretion in multiple-trauma patients receiving specialized nutritional support.

OBJECTIVE: We investigated the accuracy of methods to estimate total urinary nitrogen (TUN) excretion from urinary urea nitrogen (UUN) excretion for patients who have multiple trauma and receive specialized nutritional support. METHODS: Fifty-five critically ill, adult patients who had multiple trauma and were receiving specialized nutritional support were evaluated. A 24-h urine collection for urea nitrogen and total nitrogen was performed 4.4 +/- 2.6 d after admission to the trauma intensive care unit. Patients with significant renal impairment, liver dysfunction, or obesity (>150% of ideal body weight) were excluded from study entry. Eight publications that examined the relation between TUN and UUN were evaluated for bias and precision in estimating TUN from UUN. RESULTS: TUN was 20.8 +/- 10.8 g/d with an average difference of 3.8 +/- 2.8 g/d between TUN and UUN. Linear regression analysis comparing TUN with UUN indicated a significant correlative relation (TUN = 1.1 x UUN + 2; r = 0.958, P < 0.001). The difference between TUN and UUN varied based on UUN: for UUN lower than 10 g/d, TUN minus UUN was 1.5 +/- 1.0 g/d; for UUN 10 to 20 g/d, TUN minus UUN was 4.1 +/- 3.2 g/d; and for UUN higher than 20 g/d, TUN minus UUN was 5.3 +/- 1.9 g/d (P < 0.001). Six methods were biased toward underpredicting TUN, one method was unbiased, and one was biased toward overpredicting TUN. A practical method for estimating TUN from UUN was developed: TUN = UUN + 2 for those with UUN lower than 10 g/d and TUN = 1.1 x UUN + 2 for those with UUN of at least 10 g/d. CONCLUSIONS: Our method, the modified Velasco method, UUN/0.84, and UUN/0.85 provided reasonable estimates of TUN from UUN in critically ill, adult patients who had multiple trauma and were receiving specialized nutritional support; however, our method requires further validation.

Adult↗
PubMed1993

Measurement of true absorption, endogenous fecal excretion, urinary excretion, and retention of calcium in term infants by using a dual-tracer, stable-isotope method.

A dual-tracer, stable-isotope method was used to measure the percentage of true calcium absorption (alpha), true calcium absorption rate (Va), endogenous fecal calcium excretion rate (Vf), urinary calcium excretion rate (Vu), and calcium retention rate (Vr). Twenty-seven infants with a mean gestation of 30.6 +/- 1.7 weeks and a mean birth weight of 1.4 +/- 0.21 kg were studied at 2 or 3 weeks of age, or both, during feedings of human milk (HM), fortified human milk (HMF), and commercially available formula (20 or 24 calories per ounce) for premature infants (EPF-20/780 and EPF-24/940) (part 1 of our study). Of 13 additional infants with a mean (+/- SD) birth weight of 1.26 +/- 0.25 kg and gestation of 29.6 +/- 2.5 weeks, 11 completed a crossover-design study at 2 and 3 weeks of age, receiving two identical formulas containing calcium, 940 mg/L, and phosphorus, 470 mg/L (EPF-24/940 formula) or calcium 1340 mg/L, and phosphorus, 680 mg/L (EPF-24/1340 formula) (part 2 of our study). The alpha value was higher in infants receiving HM (76.4 +/- 15.1%) or HMF (68.0 +/- 7.8%) than in those receiving EPF-20/750 formula (54.1% +/- 5.6%) or in previously reported infants fed standard formula (47.1% +/- 11.5%); those given EPF-24/940 formula had intermediate values (63.9% +/- 13.9%, part 1; 56.1% +/- 16.5%, part 2). No significant differences existed among groups for either Vu or Vf per kilogram. In the crossover study (part 2), no significant differences were seen between formulas for alpha and for Va, Vf, or Vr per kilogram. However, Vu per kilogram was significantly decreased in infants receiving the higher mineral formula (EPF-24/940: 3.6 +/- 2.3; EPF-24/1340: 2.9 +/- 2.3 mg/kg per day; p = < 0.005). With all feedings, alpha, Vu per kilogram, and Vf per kilogram were not related to gestational age, age at study, calcium intake, or each other. However, Vf per kilogram was inversely related to birth weight. Thus, alpha, Vu, and Vf appear to be independent and may be differentially affected by factors altering calcium dynamics. We conclude that increasing formula mineral content does not ensure increased retention; careful monitoring of individual infants remains indicated.

Calcium↗
PubMed1992

Distribution and excretion of cadmium and nickel after simultaneous exposure and the effect of N-benzyl-D-glucamine dithiocarbamate on their biliary and urinary excretion.

A rat model for combined exposure to cadmium and nickel is presented that involves the administration of drinking water containing these elements over a period of 90 d. Coadministration of these two ions in drinking water leads to brain levels of both elements that are significantly higher than results from the administration of equal doses of the metals individually. The enhanced biliary excretion of cadmium in rats given sodium N-benzyl-D-glucamine dithiocarbamate (BGDTC) is almost twice as great in those animals given cadmium and nickel as in those animals given cadmium only. The excretion of nickel is reduced by the administration of this chelating agent. Although equal amounts of nickel and cadmium were administered to these animals, liver and kidney cadmium levels were approximately 100 times greater than the corresponding nickel levels. The results suggest that combined exposure to these elements may lead to enhanced levels of nickel and cadmium in the brain and a level of nervous system damage not predictable from information obtained under conditions of exposure to only one of these elements.

Administration, Oral↗
PubMed1999

Increased urinary excretion of macrophage-colony-stimulating factor (M-CSF) in patients with IgA nephropathy: tonsil stimulation enhances urinary M-CSF excretion.

Upper respiratory tract infection including chronic tonsillitis is considered to be involved in the onset and/or the progression of IgA nephropathy. It is well known that deterioration of urinary findings occurs after episodes of upper respiratory tract infection in patients with IgA nephropathy. We previously showed that the expression of macrophage-colony-stimulating factor (M-CSF) is increased in the glomeruli of patients with IgA nephropathy and correlated with glomerular mesangial proliferation, suggesting that M-CSF plays an important role in the progression of IgA nephropathy. In the present study, we measured the serum and urinary concentrations of M-CSF in patients with IgA nephropathy associated with chronic tonsillitis. Furthermore, we evaluated the effects of the local provocation test of tonsils (mechanical tonsil stimulation) on the serum and urinary concentrations of M-CSF in the following three groups: (1) IgA nephropathy with severe mesangial proliferation, (2) IgA nephropathy with mild mesangial proliferation, and (3) patients with chronic tonsillitis without renal disease. The serum and urinary levels of M-CSF in the groups with severe and mild IgA nephropathy were significantly higher than those in the chronic tonsillitis group. The urinary M-CSF level but not the serum M-CSF level was positively correlated with the degrees of mesangial proliferation and glomerular M-CSF expression in the renal biopsy specimens. The urinary M-CSF concentration was significantly increased after tonsillitis stimulation in both mild and severe IgA nephropathy groups. Enhanced urinary excretion of M-CSF prolonged for 7 days after tonsil stimulation in the severe IgA nephropathy group; in contrast, the urinay M-CSF level was increased for only 2 days after tonsil stimulation in the mild IgA nephropathy group. The urinary M-CSF level was not changed in the chronic tonsillitis group after tonsil stimulation. The serum concentrations of M-CSF were not changed after tonsil stimulation in these three groups. Our present results suggest that tonsil stimulation contributes to the progression of IgA nephropathy via enhancement of glomerular production of M-CSF. The urinary excretion of M-CSF may be a useful predictor to evaluate the relevance of chronic tonsillitis to the disease and the indication of tonsillectomy in patients with IgA nephropathy.

Adult↗
PubMed1978

Excretion of lipoteichoic acid by group A streptococci. Influence of penicillin on excretion and loss of ability to adhere to human oral mucosal cells.

Group A streptococci were grown in the presence of [2-(3)H]glycerol. Concentrated suspensions of the labeled organisms were incubated with and without penicillin. [(3)H]Glycerol-labeled material accumulated in the supernates in increasing amounts with increasing concentrations of penicillin, ranging from 0 to 50 U/ml. The excretion of labeled material occurred in the absence of nucleic acid synthesis or bacteriolysis indicating that the phenomenon is independent of cell multiplication or decay. The accumulation of label was paralleled by an accumulation of erythrocyte-sensitizing material measured by passive hemagglutination tests for lipoteichoic acid antigen, indicating that a portion of the labeled material possessed the properties of lipoteichoic acid. Culture supernates were fractionated by column chromatography, and the materials obtained were analyzed by electrophoresis on sodium dodecyl sulfate polyacrylamide, thin-layer chromatography, and paper chromatography. The ability of the same materials to bind to human erythrocytes and epithelial cells was tested. The culture supernate contained lipoteichoic acid, deacylated lipoteichoic acid, glycerol phosphate, and free glycerol. Penicillin caused an increase in the amounts of each of the excreted materials. Streptococci that were stimulated with penicillin to lose their lipoteichoic acid (previously shown to mediate adherence of group A streptococci) lost their ability to adhere to buccal mucosal cells, suggesting that penicillin may influence bacterial ecology by mechanisms other than killing sensitive organisms.

Adhesiveness↗
PubMed1991

Renal function, protein excretion, and pathology of Balkan endemic nephropathy. II. Protein excretion.

The urinary proteins of 40 patients with Balkan endemic nephropathy from the Tuzla region were examined using ultrathin-layer SDS pore-gradient polyacrylamide gel electrophoresis in combination with silver staining. The typical urinary protein spectrum contained immunoglobulin G, Tamm-Horsfall protein, transferrin, albumin, beta 2-microglobulin (beta 2m), immunoglobulin light chains, retinol-binding protein, and alpha 1-microglobulin (alpha 1m). Densitometric measurements were used to derive glomerular tubular protein ratios (GTPR) and to characterize protein excretion patterns in the 28 patients who excreted more than 150 mg/liter of protein. Results showed that proteinuria of Balkan nephropathy is predominantly tubular, consisting of low-molecular-weight species. The most commonly identified proteins were alpha 1m, light chains, retinol binding protein, and beta 2m. The pattern of proteinuria based on GTPR did not correlate with the underlying histology or the degree of renal failure. These findings, using the ultrathin-layer SDS pore-gradient method of protein separation, more accurately demonstrates the low-molecular-weight proteinuria characteristic for the early stages of BEN.

Adult↗