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Absence of mutagenicity in the urine of autopsy service workers exposed to formaldehyde: factors influencing mutagenicity testing of urine.

Hospital autopsy service workers and a matched control group were studied using a battery of genetic monitoring tests performed on samples of blood, semen and urine. The results of the analysis of urine for mutagens are described in this report. The participants in the study were matched with the controls for sex, age and their use of alcohol, tobacco and marijuana. Information was collected on general health, usage of medications and any exposure which might affect the outcome of the study. Individuals were sampled three times at approximately two month intervals. Time weighed average exposures to formaldehyde in the work areas were estimated at 0.61 to 1.32 ppm. Additionally, studies were carried out which examined various parameters affecting the testing of human urine samples for mutagenicity. No increase in mutagenicity was seen in the autopsy workers as compared to the control group. One individual who was receiving metronidazole and one control who smoked two packs of cigarettes per day had significantly mutagenic urine. A large proportion of the exposed individuals had toxic urine while only two of the control individuals had similar toxic urine. The material responsible for the toxicity has been isolated and purified but does not appear to be related to the formaldehyde exposure. Studies on the parameters affecting mutagenicity testing of urine with Salmonella typhimurium suggest that in the plate incorporation assay, TA100, but not TA98, can be affected by exogenous histidine. Furthermore, with the conditions employed in this study, 3 to 4% of labeled histidine added to urine samples was retained by the XAD-2 and subsequently eluted in the urine concentrate. Urinary histidine levels of unconcentrated samples ranged from 112 to 2614 nmol per ml (mean 994 nmol per ml) and the amount of histidine present correlated with the corresponding increases in histidine revertants with strain TA100.

Adult↗

Concentrated urine and diluted urine: the effects of citrate and magnesium on the crystallization of calcium oxalate induced in vitro by an oxalate load.

Supplementation of certain calcium crystallization inhibitors, such as citrate and magnesium, and the dilution of urine with water are now considered consolidated practice for the prevention of calcium kidney stones. The aim of this study is to verify, using tried and true in vitro methods, whether the effect of these inhibitors can manifest itself in different ways depending on whether the urine is concentrated or diluted. Calcium oxalate crystallization was studied on 4-h urine of 20 male idiopathic calcium oxalate stone formers, first under low hydration conditions (non-diluted urine) and then under high hydration conditions (diluted urine). Both the diluted and the non-diluted urine samples were subjected to three types of load: (a) an oxalate concentration increment of 1.3 mmol/l only; (b) an oxalate concentration increment of 1.3 mmol/l with a citrate concentration increment of 1.56 mmol/l; (c) an oxalate concentration increment of 1.3 mmol/l with a magnesium concentration increment of 2.08 mmol/l. In non-diluted urine, the addition of the citrate and magnesium did not modify the crystallization parameters under study. In contrast, in the diluted urine the addition of the citrate and magnesium led to a reduction in the total quantity of crystals (equivalent to 35-45%) and their aggregates (equivalent to 30-40%); at the same time, there was an increase in the diameter of the monohydrate calcium oxalate crystals, which also underwent a morphological change. In conclusion, the inhibitory effects of citrate and magnesium on the crystallization of calcium oxalate do not manifest themselves in highly concentrated urine.

Calcium Oxalate↗

Comparison of sialic acids excretion in spot urines and 24-hour-urines of children and adults.

Sialic acids comprise all N- and O-acyl derivatives of neuraminic acid and are components of glycoproteins and glycolipids. Their concentrations vary physiologically with age but also in diseases such as inflammation, neoplastic tumours or in inborn genetic disorders causing abnormal sialic acid metabolism. Determination of free and bound sialic acids in urine using the thiobarbituric acid method according to Warren (J Biol Chem 1959; 234:1971-5) was shown to be useful for the diagnosis of diseases that involve sialic acid metabolic disorders. This test-also used for the diagnosis of inborn errors of metabolic diseases, such as sialidosis, infantile sialic acid storage disease, Salla's disease, neuraminidase deficiency and others-should be included in the selective screening for storage diseases. With the reported number of mild, juvenile and adult forms of genetic disorders increasing, this diagnosis will also be useful for teenagers and adults. We therefore considered it important not to confine our investigation to children and compared the diagnostic value of 24-hour and spot urines. As shown in 24-hour urines (n = 242, 128 males, 114 females) the average excretion of sialic acids increases constantly during life, from 67.6 mumol to 444.0 mumol per day, as does the free (27.5 mumol to 217.1 mumol) and bound fraction (40.1 mumol to 226.9 mumol). The relative proportion of free and bound sialic acid shows only slight lifetime variations, the free fraction increases from about 40 percent the first few years to about 53 percent of total in the fifth decade. In the spot urines, the mean ratio of total free sialic acids and urinary creatinine (mmol/mol) decreases constantly during the first few decades, with a sharp drop during the first years of life (from 3 months-2 years: from 203.9 to 94.2 and 82.1 to 42.3 respectively; with 10 years: 52.3 and 22.4 respectively; in the sixth decade: 44.8 and 21.9). Similar findings could also be observed in the investigated 24-hour urines (correlation coefficient of ratios, R = +0.981). The comparison of 24-hour urines and spot urines confirms the reliability of results for spot urines, however, the urine collection over an extended period yields additional information.

Adolescent↗

Urine culture contamination: a College of American Pathologists Q-Probes study of contaminated urine cultures in 906 institutions.

OBJECTIVE: To examine the frequency and causes of urine culture contamination in outpatients. METHODS: Nine hundred six institutions, ranging in size from less than 50 to more than 600 beds, each examined 250 consecutively ordered urine cultures from outpatients and identified specimens that met the study definition of contamination. Participants also answered questions about the practices used to collect, transport, and process urine specimens. In all, data relating to more than 200,000 urine cultures were analyzed. RESULTS: The median institution reported that 18.1% of urine cultures specimens collected from outpatients were contaminated. The top 10% of institutions (90th percentile) reported that 5.6% or fewer of their cultures were contaminated. In contrast, the bottom 10% of institutions (10th percentile) reported that 36.8% or more of their urine specimens were contaminated. Institutions with lower contamination rates tended to process a lower proportion of specimens from female patients. Pediatric hospitals also reported lower contamination rates in specimens from children than general hospitals. Other factors, including the use of central processing areas, refrigeration, urine screening systems, specimen preservatives, provision of written collection instructions or special collection kits, and thermally insulated specimen transport containers, were not found to be associated with low specimen contamination rates in a multivariate analysis. CONCLUSION: Contamination of outpatient urine cultures is a common occurrence, and facilities differ significantly in their overall frequency of urine culture contamination. Many interventions commonly assumed to reduce contamination were not demonstrably effective in this study.

Female↗

Macrophage migration inhibitory factor is increased in the urine of patients with urinary tract infection: macrophage migration inhibitory factor-protein complexes in human urine.

PURPOSE: MIF is a proinflammatory cytokine present in preformed stores in human urothelium. In animal models of bladder inflammation, including bacterial cystitis, MIF is up-regulated in the bladder and released from the bladder as a high molecular weight complex. We compared urine MIF amounts in patients with UTI to that in patients without UTI, and we examined and identified MIF-protein complexes in urine. MATERIALS AND METHODS: Using enzyme-linked immunosorbent assay we compared MIF levels in the urine of 14 patients with UTI to levels in 16 controls with no UTI. Western blotting under native, denaturing and reducing conditions was done to examine MIF complexes found in urine. Mass spectrometry identified MIF associated proteins in urine, while co-immunoprecipitation confirmed the associations. RESULTS: Mean urine MIF amounts +/- SEM determined by enzyme-linked immunosorbent assay were significantly greater in 14 patients with UTI compared to that in 16 controls (1.96 +/- 0.40 vs 0.59 +/- 0.09 ng/mg creatinine, p <0.01). Western blotting under denaturing conditions showed several high molecular weight complexes (100 to 165 kDa) that increased in UTI urine as well as typical, monomeric MIF (12 kDa). Mass spectrometry identified associated MIF proteins, including ceruloplasmin, albumin and uromodulin. Co-immunoprecipitation confirmed mass spectrometry findings and also identified MIF interaction with alpha-2-macroglobulin. CONCLUSIONS: Increased urine MIF amounts in patients with bacterial cystitis support our experimental evidence showing a role for MIF in pelvic visceral inflammation. The novel finding of an association of MIF with other urine proteins suggest that the physiologically relevant form of MIF may be an MIF-protein complex.

Bacterial Infections↗

[The influence of daily psychosocial stressors and associated emotions on the dynamic course of urine cortisol and urine neopterin in systemic lupus erythematosus: Experience taken from two "integrative single-case studies"].

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by flare-ups, the cause of which is unknown. According to new stress concepts, two "integrative single-case studies" have been conducted in order to gather evidence about whether daily stressful incidents and associated emotions interfere with the dynamics of urine cortisol and urine neopterin in SLE. Patients under study collected their urine at home, for a period of at least 50 days, on a daily basis, divided into day and night urine. Additionally, patients filled out questionnaires twice a day to determine their emotional state, life style and disease activity. Each week, patients were examined clinically and interviewed to identify the past week's stressors using the Incidents and Hassles Inventory (IHI, Brown and Harris). Statistical analysis of the serial data was performed using time-series analysis according to Box and Jenkins. In both "integrative single-case studies" we were able to demonstrate that stressful incidents predicted an increase in urine neopterin 36 hours (Case 1) to 60 hours (Case 2) later (p < 0.05). Additionally, in Case 1 the neopterin levels were highly associated with stress resulting from the weekly examinations and interviews. Furthermore, in Case 2 it turned out that depending on their predictability stressful incidents were preceded by a decrease in urine cortisol 12 hours earlier or were followed by a decrease in urine cortisol 36 hours later. And finally, emotional irritation was highly correlated with the course of urine-neopterin. In Case 2 irritation led to an increase in urine neopterin 84 hours later. There were no clinical signs of SLE during both prospective studies. In conclusion, our results validate the idea of "integrative single-case studies" as a new "bio-psycho-social" approach in psychoneuroimmunology. Further studies with SLE patients as well as with healthy probands will be necessary in order to both strengthen and generalize these results.

Adult↗

Urine as a biological specimen for forensic analysis of alcohol and variability in the urine-to-blood relationship.

This article concerns the use of urine as a biological specimen for determination of alcohol in clinical and forensic toxicology and discusses factors that might influence variability in the urine/blood concentration ratio of alcohol. A large number of human drinking experiments were conducted to determine the time course of urine-alcohol concentrations (UAC) in relation to blood-alcohol concentrations (BAC). The UAC and BAC curves were shifted in time and the BAC curve always began to decrease before the UAC started to decline. During the early absorption phase the UAC/BAC ratio was less than unity, whereas in the late absorption/distribution period the ratio was between 1.0-1.2. On reaching the post-absorptive phase, the UAC always exceeded BAC and UAC/BAC ratios averaged 1.3-1.4, increasing appreciably as BAC decreased towards zero. Alcohol-induced diuresis was most pronounced during the rising portion of the BAC curve and near to the peak value. After about 2 hours post-drinking, the production rate of urine diminished to the pre-drinking rate of about 0.5-1 mL/min. Drinking water during the post-absorptive phase of the alcohol curve produced dilute urine, as reflected in lower creatinine content and osmolality, although the concentration of ethanol remained unchanged. After subjects drank a moderate dose of ethanol (0.54-0.85 g/kg) about 2% of the dose was recoverable in the urine after 7 hours. Ethyl glucuronide, a minor metabolite of ethanol, was measured in urine samples from drunk drivers. The UAC/BAC ratio of ethanol in drunk drivers did not depend on the creatinine content of the urine and therefore the relative dilution of the specimens. When alcohol-free urine was spiked with glucose and infected with the yeast species Candida albicans, ethanol was produced by fermentation after approximately 24 hours storage at room temperature. This post-sampling synthesis of ethanol was prevented by sodium fluoride (1% weight by volume) in the urine tubes or by keeping the specimens in the cold (4 degrees C). The UAC and BAC were highly correlated (r > 0.95) in drunk drivers and in autopsy cases, although the residual standard deviations were appreciable. This speaks against attempting to estimate BAC indirectly from UAC in any individual case. The UAC/BAC ratio and the change in UAC between two successive voids can help to resolve whether a large amount of alcohol had recently been consumed. This information is useful to support or challenge allegations of drinking alcohol after driving, which has become known as the hip-flask defence.

Area Under Curve↗

Calcium oxalate crystallization kinetics studied by oxalate-induced turbidity in fresh human urine and artificial urine.

We have studied the kinetics of oxalate-induced turbidity in fresh human urine and artificial urine. Assays are performed in 96-well plates, which allows many oxalate concentrations to be studied, repeatedly, in a short time. The metastable limit is defined in terms of the lowest oxalate concentration that gives a rate of change of attenuance significantly greater than the control. Interpretation of rates above this limit is based on ln/ln plots of initial rates against added oxalate concentration. This approach has a good theoretical basis, is well supported by our results and gives a turbidity rate index that is related to the product of the growth rate constant and a factor relating to the number and characteristics of the heteronuclei responsible for initiation of crystallization. This interpretation is posited upon the assumptions that second-order crystallization kinetics occur in unseeded urine when supersaturation exceeds the metastable limit and that aggregation during the initial phase of crystallization does not significantly contribute to changes in turbidity. Metastable limits of urine from healthy volunteers corresponded to a calcium oxalate supersaturation ratio of approx. 10. The turbidity rate index was higher in human urine than in artificial urine. The metastable limit, based on either oxalate concentration or supersaturation, for induction of calcium oxalate crystallization in normal human urine is higher than is likely to be found in normal subjects in vivo. The shape of the relationship between the metastable limit (based on oxalate concentration) and calcium concentration emphasizes the benefit of achieving a low urine calcium concentration. Comparison of the turbidity rate indices for human and artificial urine suggests that the role of nucleation promoters is more dominant than that of growth inhibitors.

Calcium↗

Serum and urine inorganic fluoride concentrations and urine oxalate concentrations following methoxyflurane anesthesia in the dog.

Plasma fluoride, urine fluoride and urine oxalate concentrations were measured before administering an anesthetic to 8 dogs, and at 0, 3, 9, 24, 48, and 72 hours following 1.5 hours of anesthesia with 1% methoxyflurane. Plasma and urine osmolalities were measured and compared with fluoride and oxalate values. Fluoride concentration increased in both plasma and urine following anesthesia when compared with the preanesthetic concentrations. Maximum mean plasma inorganic fluoride was 106.71 mumoles per liter (+/- 25.44 SE) at 9 hours after exposure to methoxyflurane was completed. By 72 hours after exposure to methoxyflurane the plasma fluoride concentration was 23.47 microM/L (+/- 5.74 SE). Mean urine inorganic fluoride concentration was highest at 9 hours after exposure to methoxyflurane and reached 6047.03 microM/L (+/- 1378.46 SE) as compared to the mean preanesthetic base-line concentration of 542.68 microM/L (+/- 132.93 SE), and the 72 hour mean urine fluoride concentration which was 1593.78 microM/L (+/- 579.46 SE). Urine oxalate concentrations, when compared with urine osmolality (mg/mOsm), increased throughout the study. The 72-hour concentration after exposure to methoxyflurane was 2.5 times the preanesthetic (mg/mOsm) oxalate concentration. Plasma osmolality did not change markedly during the study. Urine osmolalities varied between animals and collection times, but a consistent pattern did not occur. Clinical and laboratory signs of renal dysfunction were not observed in any animal during the study.

Anesthesia↗

Effect of hydrochlorothiazide on urine saturation with brushite, in vitro collagen calcification by urine, and urinary inhibitors of collagen calcification.

To clarify further the beneficial effect of thiazide diuretics on recurrent calcium nephrolithiasis, the effect of short-term hydrochlorothiazide therapy on urine saturation with brushite (CaHPO(4).2H(2)O), in vitro collagen calcification by urine, and urinary inhibitors of calcification was studied.In 22 patients with idiopathic calcium oxalate/phosphate stones the urine calcium excretion decreased, the urine magnesium excretion increased and the urine magnesium/calcium ratio increased significantly (P < 0.001) during hydrochlorothiazide therapy. Supersaturation of the urine with brushite, which was present in 19 of the 22 patients, was reduced significantly (P < 0.001) in all during thiazide therapy, and to the undersaturated range in 16. The ability of urine to calcify collagen in vitro also decreased significantly (P < 0.001) during thiazide therapy, a change that correlated significantly (r = 0.4513, P < 0.05) with the decrease in brushite saturation. The concentration of urinary inhibitors of calcification, as determined with an in vitro collagen calcification system, was decreased significantly (P < 0.01) by thiazide therapy.It was concluded that, in addition to decreasing urine calcium excretion and increasing urine magnesium excretion, thiazide diuretics decrease the urinary brushite saturation and thus may prevent spontaneous nucleation or crystal growth, or both, of calcium phosphate. The ability of thiazides to decrease collagen calcification in vitro suggests that they may also prevent crystal growth on a nidus of organic matrix. Thiazides do not appear to act by increasing the excretion of urinary inhibitors of calcification.

Adult↗

[Investigations regarding the validity of estrogen-creatine quotients from morning urine compared with those from 24-hour urine in high risk pregnancies (author's transl)].

An automated method for determining total estrogen in 24-hour urine was reported. The "estrogen-creatinine quotient" was computed in order to make the results of collective errors as independent as possible. This numerical value also makes possible comparative studies of 24-hour urine and morning urine (6:00 a.m.) as well as of urine specimens taken every two hours between 6:00 a.m. and 6:00 p.m. A total of 1000 analyses were made in 110 pregnant women; in addition, 82 daily profiles were studied. A high correlation was found between the E/C from 24-hour urine and from morning urine. In approximately two thirds of the cases, the deviation between morning urine and 24-hour urine did not exceed 10%. In the daily profiles, however, a wide variation in the daily rhythmn of some patients could be observed. According to our results, the determination of E/C in morning urine is well suited as a screening method for quick detection of estrogen elimination, particularly in high risk pregnancies.

Circadian Rhythm↗

Urine flow rates and residual urine volumes in urogynecology patients.

Two hundred and fifty consecutive women referred because of symptoms of lower urinary tract dysfunction underwent a full clinical and urodynamic assessment. Their urine flow rates and residual urine volumes were analyzed. The urine flow rates of the urogynecology patients were found to be significantly less than those of an asymptomatic population. There were significant declines in urine flow rates in the presence of a previous hysterectomy and with increasing grades of prolapse, particularly uterine prolapse, cystocele and enterocele. Unlike the normal female population, there was also deterioration with increasing parity and age, the latter largely due to the increasing incidence of hysterectomy and prolapse with age. The 10th centile of the Liverpool Nomogram for the maximum urine flow rate was found to be the most useful discriminant for a final urodynamic diagnosis of voiding difficulties. Most urogynecology patients have no or small residual urine volumes, 74% <10 ml and 81% <30 ml (vs 95% <30 ml in asymptomatic women). In urogynecology patients residuals were larger where there had been a prior hysterectomy or with grade 2 or higher uterine prolapse, cystocele and enterocele. Mean residual was 14.8 ml (vs 4.8 ml in asymptomatic women). These data indicate a higher incidence of voiding difficulties (abnormally slow urine flow (under 10th centile) and/or abnormally high residual urine volume (over 30 ml) in urogynecology patients, particularly those with higher grades of prolapse and with prior hysterectomy.

Female↗

Urine-reinfusion natriuresis: evidence for potent natriuretic factors in rat urine.

In awake rats the entire urine output was continuously reinfused i.v. Urine-reinfusion (UR) consistently led to the appearance, within one to two hours, of massive, sustained natriuresis and diuresis, suggesting the existence of potent natriuretic factors in the urine. At the time of maximal natriuresis, mean sodium excretion rate and urine flow rate were 25 and 15 times their respective values in control rats. Ths "urine-reinfusion natriuresis" could be demonstrated despite treatment with desoxycorticosterone acetate, blockage of prostaglandin synthesis by indomethacin or meclofenamate, reduction of plasma urea by pretreatment with a protein-free diet, or heating the urine to 100 degrees C. The natriuresis was not prevented by the absence of vasopressin (in Brattleboro rats) and was augmented by vasopressin infusion. In the Brattleboro rats, a marked increase in (CH2O + CNa)/GFR with only a slight rise in CH2O/GFR during UR suggests inhibition of both proximal and distal tubular reabsorption. Renal blood flow and plasma flow increased markedly during UR with a lesser rise in GFR, consistent with post-glomerular vasodilatation. Thus, the phenomenon of urine-reinfusion natriuresis suggests the presence in rat urine of potent, heat stable natriuretic factors, whose action is largely independent of changes in mineralocorticoids, prostaglandins, urea, or vasopressin. Renal vasodilatation with decreased sodium reabsorption at both proximal and distal nephron sites, appears to play an important role in the natriuresis.

Absorption↗

A method comparison study to assess the reliability of urine collection pads as a means of obtaining urine specimens from non-toilet-trained children for microbiological examination.

BACKGROUND: In young, non-toilet-trained children, the collection of a urine sample for microbiology can be challenging, with the application of a urine bag being the main method of collection. However, recent research has shown that absorbent pads can be used yielding similar results to bag specimens. However, weaknesses in study design erode confidence in research findings. Therefore, improvements in research design are required to fully evaluate the reliability of pad collection. AIMS OF THE STUDY: This pilot study sought to test the feasibility of a technique for the collection of concurrent bag/pad urine samples from non-toilet-trained children, and to assess the reliability of urine pads over bags as a collection method for urine specimens for microbiological evaluation. DESIGN: A pilot, method comparison study. METHODS: Twenty concurrent bag and pad specimens were collected from non-toilet-trained children, following parental consent. Urine specimens were analysed for presence or absence of white cell count (WBC), and bacterial growth, using standard laboratory methods. DATA ANALYSIS: The Kappa (kappa) statistics and confidence interval (CI) estimation were used to assess agreement between the two collection methods. RESULTS: Despite concurrent samples there was a lack of agreement between bag and pad specimens on both main outcome measures. Agreement between bag and pad specimens for the presence of WBC yielded a kappa=0.10 (95% CI: 0.19, 0.39), indicating poor agreement, while a kappa of 0.5 (95% CI: 0.12, 0.88) was calculated for the degree of agreement in bacterial growth reflecting moderate agreement. Differences in proportions of the presence of WBC between bag and pad did not quite reach significance at the 5% level 0.2 (95% CI: 0.00, 0.42, P=0.062). For cultures the difference was calculated as 0.15 (95% CI: 0.05, 0.35, P=0.125). CONCLUSION: The pilot study demonstrates that concurrent urine samples can be obtained without difficulty. Despite poor to moderate agreement on outcome measures the level of agreement is greater than reported in those other studies, that use non-current methods of urine collection, suggesting an advantage of the concurrent technique. It is recommended that larger scale studies be undertaken using the concurrent collection technique to assess reliability of these findings.

Child, Preschool↗

Comparison of urine contamination rates using three different methods of collection: clean-catch, cotton wool pad and urine bag.

Collecting uncontaminated urine specimens from infants is difficult. Commonly, an adhesive urinecollecting bag is used, which is uncomfortable. This study determined bacterial contamination rates using three methods of urine collection sequentially on the same infant (without known urinary tract infection)-clean-catch, cotton wool (sanitary) pad and urine bag. The study was undertaken in children under 3 years of age in the Institute of Maternal and Child Health of Pernambuco (IMIP), Recife, Brazil. Urine samples were analysed using phase contrast microscopy and routine culture. Culture of bacteria at any level was interpreted as a contaminated urine specimen. Cultures with > 10(5) colony-forming units/ml of one species by all three collection methods were regarded as true urinary tract infection and these children were excluded. Altogether, 534 urine samples from 191 patients were analysed. Median age was 2 months (1 day-36 months) and 124 (65%) were boys. Twelve children (6.3%) were considered to have true urinary tract infection, three were indeterminate and in 16 one or more samples were missing and all were excluded from analysis. There were more missing samples using the clean-catch method (12%) than when using the bag (4%) or pad (4%). Seventy-six of 160 (47.5%) children had evidence of bacterial contamination. Clean-catch specimens showed the least contamination (14.7%) and rates were similar between pads (29%) and bags (26.6%) (kappa = 0.40). Urine contamination rates were similar for sanitary pads and urine bags and significantly higher than for clean-catch (p<0.01). However, pads were a simple, non-invasive and comfortable alternative to bags.

Child, Preschool↗

[The SOS-inhibition activity of human urine investigated by umu-test--diurnal and daily changes of SOS-inhibition activity of urine].

We found that human urine suppressed SOS-responses induced by furylfuramide (AF-2), as detected by the umu test using Salmonella typhimurium TA1535/pSK1002. In the present report, we studied the time stability of the SOS-inhibition activity in urine. The diurnal and daily changes of SOS-inhibition in the urine were also observed. Results obtained were as follows; 1) SOS-inhibition activity of the urine remained stable more than one month after the urine was frozen. 2) Individual variation was observed in the SOS-inhibition activity of the urine. 3) Total SOS-inhibition activity of per a day showed relatively small variation during experimental days. 4) The SOS-inhibition activity of urine was higher early in the morning than in the daytime. The activity fell gradually with time in the daytime and showed the lowest value in the evening. Then, it rose again at night. Therefore, it is necessary to collect urine at specific times to avoid the differences caused by diurnal changes in SOS-inhibition activity.

Adult↗

Excretion of endogenous digoxin-like immunoreactive factors in human urine is a function of urine flow rate.

We studied the effect of varying water and salt intake on the renal excretion of endogenous digoxin-like immunoreactive factors (DLIF). DLIF were measured in human urine and serum by competitive displacement of 125I-labeled digoxin from anti-digoxin antibodies. Diuresis was selectively induced in normal healthy humans by acute water ingestion, and natriuresis was preferentially induced by acute saline ingestion. We found the amount of endogenous immunoreactivity excreted in urine to be correlated with urine flow rate but not with urinary sodium excretion. Urinary excretion of DLIF, normalized to creatinine, was 3.6-fold greater at a urine flow rate of 5.5 mL/min than at 0.5 mL/min. On the other hand, saline intake increased urine flow rate 1.9-fold and increased sodium excretion threefold, but did not affect urinary excretion of DLIF. Fractional excretion of DLIF was linearly related to fractional excretion of water. This study demonstrates that normalization of DLIF values to urinary creatinine does not make DLIF excretion independent of urine flow rate and underscores the need for information on urine flow rate when DLIF measurements in urine are being interpreted.

Blood Proteins↗