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PubMed1998

Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: the Strong Heart Study.

Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (> or = 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA1c, study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin.

Aged↗
PubMed2005

Small increases in the urinary excretion of glutathione S-transferase A1 and P1 after cardiac surgery are not associated with clinically relevant renal injury.

OBJECTIVE: Cardiac surgery is an important risk factor for the development of acute renal failure. Cytosolic enzymes glutathione S-transferase (GST) A1 and P1 are present selectively in proximal and distal tubular cells, respectively. We determined the extent and site of tubular injury and examined if GST excretion may predict a clinically relevant change in renal function. DESIGN AND SETTING: A prospective, observational study in 84 consecutive patients in the cardiac surgery intensive care unit of the University Medical Centre Nijmegen. MEASUREMENTS AND RESULTS: Urinary GST enzyme excretion was determined 0-4 h and 20-24 h after cardiac surgery by enzyme-linked immunosorbent assay. Data are expressed as median and 5-95% range. Urinary excretion of GSTA1 was increased: 1.25 microg/mmol [0.31-10.20] creatinine at t =0-4 h ( p <0.0001, compared with controls; 0.25 [0.1-0.8]) and returned to normal values at t =20-24 h. Excretion of GSTP1 was 2.11 microg/mmol [0.52-17.82] creatinine ( p <0.0001) at t =0-4 h and remained significantly elevated: 0.84 [0.30-16.86] at t =20-24 h ( p =0.01) compared with controls (0.5 [0.2-1.1]). The ten patients with the highest urinary excretion of GSTA1 or GSTP1 did not demonstrate a different plasma creatinine level on postoperative day 3, compared with the ten patients with the lowest urinary excretion of GSTA1 or GSTP1. CONCLUSION: Uncomplicated cardiac surgery results in a statistically significant increase in the urinary excretion of GSTA1 and GSTP1 as compared with healthy controls, indicating proximal and distal tubular damage. However, this small increase in urinary excretion of GSTs is not associated with clinically relevant renal injury.

Acute Kidney Injury↗
PubMed1994

Biliary excretion of exogenous cadmium and manganese in Long-Evans Cinnamon (LEC) rats characterized by an inherently gross amount of copper-metallothionein in the liver.

Long-Evans Cinnamon (LEC) rats are characterized by the sudden onset of hepatitis around 4 months after birth and the gross accumulation of hepatic copper (Cu) accompanied by metallothionein (MT). The biliary excretion of manganese (Mn) and cadmium (Cd) injected intravenously was studied in 3-month-old LEC rats without signs of hepatitis. Injected Mn was excreted into the bile in LEC and Fischer rats used for comparison. However, increased biliary excretion of Cd was found not in the LEC rat but in the Fischer rat. Excretion of horseradish peroxidase (HRP) injected along with the metal mixture was significantly lower in the LEC group than in the Fischer group. Our results suggest that Mn excretion is not related to the existence of a gross amount of Cu-MT. Reduced excretion of Cd may be partly due to binding to Cu-MT in the liver. Decreased excretion of HRP implies the existence of an inherent defect in the bile excretion route for endo- and exogenous substances.

Animals↗
PubMed2005

Significant intestinal excretion, one source of variability in pharmacokinetics of COL-3, a chemically modified tetracycline.

PURPOSE: This study was undertaken to examine the disposition of COL-3, a chemically modified tetracycline, in order to elucidate its major route of elimination as one possible source of the variability in pharmacokinetics of COL-3 in vivo. METHODS: The disposition profile of COL-3 in vivo was assessed by examining the urinary and fecal excretion of the unchanged drug and/or its metabolites in rats after single intravenous and oral administration. The biliary excretion of COL-3 administered orally in bile duct-cannulated rats was also examined. In addition, plasma protein binding and cytochromes P450-mediated metabolism were explored along with erythrocyte partitioning in vivo. Furthermore, transport of COL-3 across Caco-2 monolayers was performed to elucidate the mechanism of intestinal excretion of COL-3 in vivo. RESULTS: COL-3 was extensively bound to plasma protein in rat (98%) and human plasma (95%). The affinity of rat blood cells for COL-3, as measured by the ratio of drug concentration in blood cells to that unbound in plasma, was about 36. Of the single intravenous and oral doses, less than 0.2% and 0.03% were excreted unchanged in rat urine, respectively; while 32.1 +/- 9.9% and 38.8 +/- 6.1% were recovered unchanged in rat feces, respectively, within 48 h postdosing. Of the oral dose, 1.36 +/- 0.66% and 2.97 +/- 0.88% were excreted in rat bile as the unchanged COL-3 and the total of COL-3 and its glucuronide conjugate, respectively, within 24 h after dosing. COL-3 had insignificant cytochrome P450-mediated metabolism but underwent phase II metabolism (i.e., glucuronidation) in a minor quantity. COL-3 was not a substrate of P-glycoprotein. Its transport across Caco-2 monolayers was significantly affected by protein binding and pH. CONCLUSIONS: Intestinal excretion, a route different from biliary excretion, is the major route of elimination for COL-3 in rats. Variability in intestinal excretion, due to extreme variable intestinal contents (food and digestive fluids), could be one source of variability in COL-3 pharmacokinetics in vivo in addition to the dissolution rate-limited absorption.

Animals↗
PubMed1985

Characteristics of proton excretion in normal and acidotic toad urinary bladder.

This study, performed on the urinary bladder of Bufo marinus, was to investigate the characteristics of H+ excretion in the normal and metabolic acidotic toad. Experiments were run in modified Ussing chambers in the presence and absence of exogenous CO2. Amiloride in the mucosal medium (1.5 X 10(-4) M) inhibited H+ excretion in the acidotic bladder but this inhibition was reversed in the presence of 5% CO2. Na+-free mucosal medium revealed a component of H+ excretion in the normal toad that is Na+-dependent and not reversed by 5% CO2. Acetazolamide (10(-3) M) had no effect on H+ excretion in normal toad but inhibits excretion in the acidotic toad both in the presence and absence of exogenous CO2. In both the presence and absence of exogenous CO2 and in the presence of varying pH gradients, the bladders from acidotic toads excreted H+ at a greater rate and were able to generate greater pH gradients than in normal bladders. Voltage clamp experiments revealed that H+ excretion in the acidotic toad was inhibited by a mucosal potential difference of -20 to -100 mV but this inhibition was completely reversed by 5% CO2. In the normal toad bladder H+ excretion was stimulated by a mucosal potential difference of -20 to -100 mV in both the presence and absence of exogenous CO2. Our evidence suggests the possibility of two H+ excretory mechanisms in toad urinary bladder each with its' own set of characteristics dependent on the acid-base state of the animal. Proposed models are presented for these mechanisms.

Acidosis↗
PubMed1984

Urinary excretion of dimethylarginines in premature infants.

Urinary excretion of NG,N'G-dimethylarginine (NG,N'G-Me2Arg) and NG,NG-dimethylarginine (NG,NG-Me2Arg) was measured in premature infants. The NG,N'G-Me2Arg/NG,NG-Me2Arg ratio was much higher in newborn infants than in older children or adults. Linear regression analysis showed a significant negative correlation between the degree of maturity and the excretion of NG,N'G-Me2Arg. A significant direct linear relationship also was found between the excretion of NG,N'G-Me2Arg and the rate of whole body nitrogen flux and of protein synthesis and catabolism. No correlation was found between the excretion of the dimethylarginines and 3-methylhistidine, but the dimethylarginine/3-methylhistidine ratio declined with advancing conceptual age. A direct linear relationship was found between excretion of NG,N'G-Me2Arg and NG,NG-Me2Arg and whole body nonskeletal muscle protein breakdown. No correlation was found between nonskeletal muscle protein catabolism and 3-methylhistidine excretion. We estimate that approximately 0.34 mumole of dimethylarginine are excreted per gram of nonskeletal muscle protein catabolized. Dietary intake did not affect the excretion of either NG,N'G-Me2Arg or NG,NG-Me2Arg. The data suggest that measurement of urinary dimethylarginines might be useful in the nutritional assessment of premature infants.

Adolescent↗
PubMed1984

Drug elimination function of rat small intestine: metabolism and intraluminal excretion.

The metabolic and excretory function of the small intestine was investigated after oral and intravenous administration of drugs having an aromatic amino group to rats. After administration of drugs into the intestinal loop at the initial concentration of 0.1 mM, significant excretion of their N-acetylated forms into the lumen was observed. The amount of N-acetyl forms excreted in the lumen were 39.3 +/- 3.5, 63.5 +/- 20.9 and 18.0 +/- 13.8% of disappeared drugs from the lumen for p-aminobenzoic acid (PABA), p-aminosalicylic acid and sulfanilic acid, respectively. The excretion of p-acetamidobenzoic acid (Ac-PABA) after the absorption of PABA was reduced by the coadministration with salicylic acid, benzoic acid and 2,4-dinitrophenol. Salicylic acid noncompetitively inhibited the acetylation of PABA by the intestinal N-acetyltransferase. A good correlation was found between the intestinal N-acetyltransferase activities for drugs and the intraluminal excretion of N-acetyl derivatives after intestinal absorption of drugs. These results indicate that a drug having a higher susceptibility to intestinal N-acetyltransferase would undergo a greater excretion into the lumen in its N-acetyl form after intestinal absorption. After intravenous administration of PABA at a dose of 100 mumole/kg, 4.02 +/- 0.51% of dose was excreted in the lumen as Ac-PABA in 30 min. On the other hand, a significantly smaller fraction (2.72 +/- 0.68% of dose) was excreted in the lumen after intravenous injection of 100 mumole/kg of Ac-PABA. The larger excretion of Ac-PABA after administration of PABA indicates the contribution of intestinal metabolism on the transfer of PABA not only after oral, but also after intravenous administration.

4-Aminobenzoic Acid↗
PubMed1991

Glutathione-dependent biliary excretion of arsenic.

This study aimed to clarify whether glutathione (GSH) plays a role in the hepatobiliary transport of arsenic. For this purpose, the biliary excretion of 74As was measured in urethane-anaesthetized rats for 2 hr after the administration of labelled sodium arsenite (50 mumol/kg, i.v.) or arsenate (150 mumol/kg, i.v.) and under the influence of sulfobromophthalein (BSP), indocyanine green (ICG) or diethyl maleate (DEM) which are known to diminish hepatobiliary transport of GSH. Although the biliary excretion of arsenic was different after arsenite and arsenate administration in terms of quantity (19% vs 6% of dose in 2 hr, respectively) and time course, arsenic excretion responded similarly to BSP (50 mumol/kg, i.v.), ICG (25 mumol/kg, i.v.) or DEM (4 mumol/kg, i.p.) irrespective of the injected arsenical. Initially the biliary excretion of arsenic in rats with either arsenite or arsenate was significantly reduced, but then moderately increased by BSP and, more lastingly, depressed by ICG, whereas it was virtually abolished by DEM. The responses of arsenic excretion to BSP, ICG and DEM were related, both proportionally and temporally, to the effects exerted by these agents on the hepatobiliary transport of GSH, as assessed by the biliary excretion of non-protein thiols. These findings indicate that the biliary excretion of arsenic after the administration of either arsenite or arsenate is dependent on the hepatobiliary transport of GSH. Transport of arsenic as a GSH complex may account for the GSH dependence of biliary arsenic excretion.

Animals↗
PubMed1991

Biliary excretion of polyethylene glycol molecular weight 900. Evidence for a bile salt-stimulated vesicular transport mechanism.

Polyethylene glycol molecular weight 900 (PEG-900) has been used as a marker of vectorial water transport into bile canaliculus. However, the mechanisms by which this compound is excreted have not been clarified. To gain more information on this process, we studied the biliary excretion of [3H]PEG-900 in rats during choleresis induced by canalicular choleretics. In addition, the effects of the microtubule inhibitors colchicine and vinblastine, and of the acidotropic agent chloroquine, on PEG-900 excretion were studied to determine whether a vesicular pathway is involved. Continuous i.v. infusion of either dehydrocholate (DHC, a non-micelle forming bile salt choleretic) or 4-methylumbelliferone (4-MU, a non-bile salt canalicular choleretic) at stepwise-increasing rates [0.7, 1.0 and 1.2 mumol.min-1.(100 g body wt)-1] induced a gradual increment in bile flow, whereas a transient increment of [3H]PEG-900 excretion was observed only during DHC-induced choleresis. Furthermore, studies in which two consecutive i.v. injections of DHC (10 mumol/100 g body wt) were administered showed that [3H]PEG-900 excretion induced by a second administration of DHC was 54% lower than that induced by the first one, despite a similar excretion in bile flow. Finally, colchicine (0.5 mumol/100 g body wt), vinblastine (0.5 mumol/100 g body wt) and chloroquine (50 mg/kg body wt) pretreatments inhibited the DHC-induced increment in biliary [3H]PEG-900 output, while DHC-induced choleresis was almost unaffected. Conversely, excretion of [14C]sucrose, when coadministered with [3H]PEG-900, was not impaired by the treatments. These results suggest that, unlike sucrose, PEG-900 excretion is not associated with canalicular water movements. Instead, it may be related to a vesicular transport process followed by a bile acid-stimulated discharge of secretory vesicles into bile through the lysosomal compartment.

Animals↗
PubMed1990

Fourier analysis of biliary and pancreatic excretion in man based on data obtained by a duodenal perfusion/aspiration technique.

A standard duodenal perfusion/aspiration technique was used to continuously monitor biliary and pancreatic excretion in young healthy human subjects, and the excretory patterns were examined by Fourier power spectral analysis. Experiments were carried out in the fasting state, either without or during a continuous parenteral (i.v.) stimulation by secretin and the cholecystokinin analogue ceruletide. The duodenal content aspirated was either discarded after sampling or reinfused into the jejunum. In the fasting state, significant biliary and pancreatic excretion was detected, fluctuating with a periodicity of about 60 min. During parenteral infusion with ceruletide/secretin, to simulate a postprandial state, the rate of biliary and pancreatic excretion increased as compared with fasting levels alone (basal levels). A dominant period of about 60 min was still detected but second periods of approximately 45 min and approximately 95 min, respectively, were also observed. The peak power and the total power of the biliary excretion signals were reduced. Reinfusion of aspirated duodenal fluid into the intestine (jejunum) led to a further decrease in peak power and total power of the known biliary signals. Trypsin excretion into the duodenum revealed mainly insignificant changes in peak and total power upon hormone stimulation despite a definite increase in total amount of trypsin excreted. The results indicate that parenteral ceruletide/secretin stimulation has a stabilizing effect on biliary excretion in man, and that reinfusion of aspirated duodenal content into the intestine further stabilizes the excretion.

Adult↗
PubMed1975

Increased sterol excretion with polyunsaturated-fat high-cholesterol diets.

Previous studies have shown that polyunsaturated ruminant fats in the diets of human subjects cause an increase in cholesterol and bile acid excretion during the first 3 weeks of such diets. The present studies were designed to compare the effects of polyunsaturated (P) and conventional (S) ruminant fats at two levels of dietary cholesterol intake: a higher (HC) and lower (LC). Four study periods, each of about 3 weeks' duration, were conducted in 5 healthy subjects providing these dietary combinations: HCS, HCP, LCS, LCP. Neutral sterols and bile acids were measured in the feces, and sterol balances were calculated. Plasma cholesterol levels were significantly lower with P than with S diets at both HC and LC intakes. Changes attributable to differences in fatty acids and to differences in cholesterol intake appeared to exert independent effects. The major changes occurred in lipoproteins with density 1.019-1.045. Cholesterol absorption expressed as a percentage of the dietary intake was not significantly different with the four diets. Neutral sterol excretion of probable endogenous origin and bile acid excretion were significantly higher during the HCP than during the HCS periods, but the difference between LCP and LCS periods was less marked. Net sterol excretion was therefore significantly greater with HCP and LCP than with HCS and LCS diets, the differences being greater at HC than at LC intakes. Comparisons of diets with similar fatty acid but differing cholesterol intakes showed lower net sterol excretion with HCS than with LCS diets (presumably due to suppression by HC by cholesterol synthesis), but this difference was not seen between HCP and LCP diets. This finding, together with greater sterol excretion with HCP than with HCS diets, showed that enhanced sterol excretion with polyunsaturated fat was potentiated with higher cholesterol intake. This enhanced excretion was generally greater during the first than during the second 3-week period of polyunsaturated fat.

Adolescent↗
PubMed1976

Comparative effects of glycerol and dextrose on porphyrin precursor excretion in acute intermittent porphyria.

The effects of dietary manipulations on excretion of the porphyrin precursors, delta-aminolevulinic acid (ALA), and porphobilinogen (PBG) were studied in eight patients with acute intermittent porphyria. Three diet periods of 9-17 days comprised each study. In each patient, a "baseline" protein, fat, and carbohydrate intake was kept constant throughout. In addition, during the first diet period each patient received 150 g dextrose; during the second, this was replaced by an isocaloric amount of neutral fat; and during the third, the fat was replaced by 150 g glycerol. In each of the patients, three comparisons of the effect of diet on both ALA and PBG excretion were made: (1) 300 g carbohydrate versus 150 g carbohydrate (dextrose versus fat), (2) 150 g carbohydrate + 150 g glycerol versus 150 g carbohydrate (glycerol versus fat), and (3) 300 g carbohydrate versus 150 g carbohydrate + 150 g glycerol (dextrose versus glycerol). For each of these three diet comparisons, there are sixteen individual comparisons possible for the effect of diet on porphyrin precursor excretion, eight for ALA and eight for PBG. Thus, the mean values for ALA and PBG excretions during each of the diet periods are statistically compared internally within each individual patient. Increasing carbohydrate intake from 150 g to 300 g by isocaloric substitution of dextrose for fat produced a significant (p less than 0.05) decline in eight of the sixteen comparisons of ALA and PBG excretion. Addition of 150 g glycerol by isocaloric substitution for fat caused a significant (p less than 0.05) decline in nine of the sixteen possible comparisons. In the sixteen comparisons of isocaloric dextrose and isocaloric glycerol-substituted diets, dextrose produced significantly (p less than 0.05) lower porphyrin precursor excretion in four cases and glycerol produced significantly (p less than 0.05) lower values in five. One patient showed no significant change on any of the diets. Of the four patients having symptoms believed referrable to porphyria during the study, three reported an improvement in symptoms during the high glycerol intake. The effects of dietary perturbations on porphyrin precursor excretion in acute intermittent porphyria are variable, but glycerol appears to be capable of decreasing the excretions and may prove useful in treating some of these patients.

Acute Disease↗
PubMed1993

Urinary excretion of polyamines in patients with surgical and accidental trauma: effect of total parenteral nutrition.

Excretion of polyamines first increases and then decreases in patients with multiple trauma receiving total parenteral nutrition (TPN). To separate the effects of trauma and TPN on polyamine excretion, we studied 12 patients with multiple trauma and 14 patients after surgery for colorectal malignancy. Patients were randomized to receive either TPN or hypocaloric glucose infusion. Urinary excretion of total and free polyamines, putrescine (PU), spermidine (SPD), and spermine (SP), and their metabolites, N1-acetylspermidine (N1-AcSPD) and N8-acetylspermidine (N8-AcSPD), and energy and nitrogen balance were measured. Polyamine excretion, excluding SP, markedly increased after trauma and surgery, exceeding the normal values by twofold to 10-fold. In patients receiving TPN, the excretion of total polyamines was 48% higher (P < .01), PU was 34% higher (P < .05), SPD was 35% higher (P < .05), and SP was 350% higher (P < .05) than in patients receiving hypocaloric glucose. Urinary excretion of SP was only 17% of the reference value during hypocaloric glucose (P < .05), but was normal during TPN. The difference in polyamine excretion between nutrition groups was more pronounced when normalized for nitrogen or energy balance. Patients receiving TPN were more hypermetabolic than patients receiving hypocaloric glucose (resting energy expenditure, 1.36 +/- 0.06 [SE] and 1.16 +/- 0.04 times predicted values, respectively; P < .025). Statistically, energy expenditure could explain the difference in polyamine excretion between nutrition groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

19-Nordeoxycorticosterone, aldosterone, and corticosterone excretion in sequential urine samples from male and female rats.

19-Nordeoxycorticosterone (19-norDOC) is a powerful mineralocorticoid that has been postulated to play a role in the pathogenesis of some forms of hypertension in the rat. We measured the daily excretion of 19-norDOC, aldosterone, and corticosterone in intact male and female SR/jr rats for 20 consecutive days. The excretion of corticosterone and aldosterone was higher during the first 4 days of collection and remained relatively stable for the rest of the collection period. The excretion of corticosterone and aldosterone was not different between male and female rats. The excretion of 19-norDOC, which, as has been reported previously, was significantly higher in female than male rats, varied over 600% from day to day in some individual rats. The variability in the excretion of 19-norDOC did not correlate with the excretion of aldosterone or corticosterone and did not appear to coincide with an estrous cycle. These studies also indicate that when the urinary excretion of steroids is intended to be used as an indication of steroid production in the basal state, a period of at least 4 days of acclimatization in metabolic cages, even for animals accustomed to handling, is necessary to obtain stable excretions.

Aldosterone↗
PubMed1992

Effect of lipoic acid on biliary excretion of glutathione and metals.

Several metals are excreted in bile as glutathione complexes, and their biliary excretion is facilitated by increased hepatobiliary transport of glutathione. The present study analyzed the effect of lipoic acid (LA; thioctic acid; 37.5-300 mumol/kg, iv), an endogenous disulfide which can be reduced in vivo to a dithiol, on the hepatobiliary disposition of glutathione-related thiols and the biliary excretion of metals (10 mumol/kg, iv) in rats. Administration of LA enhanced the biliary excretion of reduced glutathione in a dose-dependent fashion. Despite increasing glutathione output, LA (150 mumol/kg, iv) did not increase, but rather decreased, the biliary excretion of methylmercury, cadmium, zinc, and copper, which are transported into bile in a glutathione-dependent manner, as indicated by a marked reduction in their biliary excretion after diethyl maleate-induced glutathione depletion. In contrast, biliary excretion of inorganic mercury, which is minimally affected by glutathione depletion, was dramatically enhanced (12- to 37-fold) by LA administration. Following injection of LA, the concentrations of endogenous disulfides in arterial blood plasma (e.g., cystine, glutathione disulfide, cysteine-glutathione, protein-cysteine, and protein-glutathione mixed disulfides) were considerably diminished, while the levels of endogenous thiols (e.g., glutathione and cysteine) were increased. This finding indicates that LA, probably after enzymatic conversion to dihydrolipoic acid, can reduce endogenous disulfides to thiols. It appears that LA induces the transport of glutathione into bile by the temporary formation of dihydrolipoic acid-glutathione mixed disulfide, which after being translocated into bile is cleaved to LA and reduced glutathione. Because the glutathione molecule thus transported into bile cannot complex metals at the thiol group, this might be the mechanism for the observed failure of the LA-induced increase in biliary excretion of glutathione to enhance the hepatobiliary transport of metals that are transported into bile as glutathione complexes (i.e., methylmercury, cadmium, zinc, and copper). The observations also raise the possibility that endogenous dihydrolipoic acid, by forming a stable complex with mercuric ion, may play the role of a carrier molecule in the hepatobiliary transport of inorganic mercury.

Animals↗
PubMed1977

Urinary excretion of immunoreactive prostaglandin E: a circadian rhythm and the effect of posture.

The excretion of urinary immunoreactive prostaglandin E (iPGE), sodium, potassium, creatinine and volume was studied in 4 hr collections in normal women at normal activity. iPGE exhibited a circadian rhythm with an amplitude of 29% and peak excretion at 4:55 P. M. There were also significant circadian rhythms for sodium, potassium, creatinine, and volume, all peaking in late afternoon. There were no significant changes either in the total excretion or in the circadian rhythms of iPGE, potassium, or creatinine excretion when the subjects remained in bed for an entire day while the circadian rhythms of sodium and volume were significantly modified in amplitude and phase, respectively. Urinary aldosterone excretion decreased significantly when the subjects were at bed rest. iPGE excretion increased 33% when subjects were first recumbent and then erect for consecutive 4 hr period on the same day (but when subjects were erect 1 day for a 4 hr period, iPGE excretion was lower by 32% than for the same 4 hr period the preceding day when they were recumbent). These data indicate that: 1) the sympathetic nervous system and renin-angiotensin-aldosterone system do not affect the circadian rhythms of urinary iPGE, and 2) short-term experiments of prostaglandin E excretion must be designed to avoid misleading results due to the circadian rhythm.

Adult↗
PubMed1984

Urinary excretion of 2,3-dinor-thromboxane B2 in man under normal conditions, following drugs and during some pathological conditions.

Quantitation of 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2) was performed by gas chromatography-mass spectrometry. Under normal conditions the urinary excretion of 2,3-dinor-TxB2 was relatively constant in the same individual from day to day but during a 24-hour period a somewhat higher excretion rate was found during the first few hours after awakening. A pronounced reduction of the urinary excretion of 2,3-dinor-TxB2 was found after oral administration of 500 mg of aspirin or 50 mg of indomethacin, while 500 mg of paracetamol did not affect the urinary excretion. Increased excretion of 2,3-dinor-TxB2 was found in normal pregnancies and in diseases such as diabetes mellitus and homocysteinuria in comparison to the urinary excretion in normal healthy subjects. We also report one case, where the urinary excretion of 2,3-dinor-TxB2 was increased for a short period following the first symptoms of a myocardial infarction and those data indicate that thromboxane A2 (TxA2) may be of pathophysiological importance in human myocardial infarction. The results strongly indicate that measurements of the urinary excretion of 2,3-dinor-TxB2 should be meaningful as a tool for investigation of the involvement of thromboxane in various pathophysiological processes in vivo in man.

Acetaminophen↗
PubMed1990

Urinary excretion patterns of endogenously produced alcohols in type 1 (IDDM) and type 2 (NIDDM) diabetes mellitus compared with healthy control subjects.

Urinary excretion patterns of various endogenously produced alcohols, such as ethanol, propanol, isobutanol, butanol, and isopentanol, were evaluated in 17 type 1 (IDDM) and 15 type 2 (NIDDM) diabetic patients, and in two different groups of healthy control subjects (n = 12, n = 8, respectively) matched for sex, age and weight. In addition to the urinary alcohol excretion determined by gas-chromatography and mass-spectrometry, four cardiovascular reflex tests were performed, and the motor and sensory conduction velocities of three different peripheral nerves were measured. In the type 1 diabetic patients, urinary excretions of ethanol and propanol were significantly higher than in the control subjects (P less than 0.0001, P less than 0.00001, respectively), whereas the control subjects exhibited significantly higher urinary excretion rates of the other three alcohols (P less than 0.007, P less than 0.02 and P less than 0.002, respectively) compared with the type 1 diabetic patients. In the type 2 diabetic patients, only the urinary excretion of propanol was significantly elevated (P less than 0.002) compared with the control subjects, while the urinary excretion rates of butanol and isopentanol were significantly lower (P less than 0.02, P less than 0.05, respectively) than in the controls. Urinary alcohol excretions were not related to diabetic peripheral neuropathy in both groups studied. The clinical meaning of the urinary excretion patterns of different endogenously produced alcohols in diabetes mellitus has to be further evaluated.

Adult↗