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Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus.

AIM: We tried to establish the significance of quantifying urinary type IV collagen (IV-C) excretion for the evaluation of renal involvement of type 2-diabetic patients. METHODS: Twenty patients (13 males and 7 females; age range 31 to 69 years) with type 2 diabetes mellitus had undergone renal biopsy and relationship between the severity of morphological alteration, IV-C expression and urinary IV-C excretion were examined. RESULTS: Urinary IV-C excretion significantly correlated with mesangial expansion score (p = 0.49, p < 0.05) and tubulointerstitial injury score (p = 0.56, p < 0.05). Furthermore, urinary IV-C excretion significantly correlated with both glomerular (r = 0.56, p < 0.01) and tubulointerstitial IV-C expression areas. Urinary protein excretion also correlated with mesangial expansion score and tubulointerstitial injury score. However, it did not correlate with the expression of IV-C in the kidney. CONCLUSIONS: These results suggest that urinary IV-C excretion reflects the pathogenetic process of diabetic nephropathy, which urinary protein excretion alone cannot do sufficiently. It can be concluded that urinary IV-C excretion could be a more useful marker for the evaluation of renal involvement of type 2-diabetic patients.

Adult↗

Changes in urinary excretion of deoxypyridinoline in tail-suspended rats: effects of a bisphosphonate, YH529.

Urinary excretion of deoxypyridinoline (D-Pyr) has been shown to be a useful marker for bone resorption. In this study, we investigated whether D-Pyr could be used to monitor the changes in bone resorption of the hind limb induced by tail-suspension. Male Wistar rats 5-weeks old were tail-suspended in a metabolic cage to unload the hind limbs. The control rats were not suspended. YH529 (YH), an inhibitor of bone resorption, or a vehicle (phosphate buffered saline=PBS) was administered daily starting 3 days before the commencement of tail-suspension. In the non-suspended rats receiving PBS, urinary excretion of D-Pyr did not show any significant change during the one-week experimental period. In the non-suspended rats receiving YH, D-Pyr excretion significantly decreased on day 5 and 7 when compared with that observed on day 0, in accordance with the systemic inhibition of bone resorption by YH. In the tail-suspended rats receiving PBS, D-Pyr excretion showed a tendency to increase on day 1, which is in agreement with our previous report that tail-suspension causes an early (on day 1 of suspension) and transient increase in bone-resorption of the hind limbs. In the tail-suspended rats treated with YH, the increase in D-Pyr excretion on day 1 was not observed, and a significantly lower excretion was noted from day 3 to 7 during the tail-suspension. It was suggested that D-Pyr excretion might reflect the transient increase in hind limb bone resorption induced by tail-suspension. As observed in-YH treated rats, D-Pyr excretion could serve as a good marker for the inhibition of systemic bone resorption.

Amino Acids↗

Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai.

Although the majority of ecological and experimental studies have suggested a potential role of phytoestrogens in breast cancer prevention, findings from epidemiological studies have been inconsistent. Part of the inconsistencies may be attributable to the difficulty in measuring intake levels of phytoestrogens. Overnight urine samples from 250 incident breast cancer cases and their individually matched controls were analyzed for urinary excretion rates of isoflavonoids, mammalian lignans, and citrus flavonoids. The study subjects were a subset of the participants in the Shanghai Breast Cancer Study, a large population-based case-control study conducted in Shanghai from 1996-1998. To minimize potential influence of treatment on the exposure of interest, urine samples from breast cancer cases were collected before cancer therapy. Urinary excretion of total isoflavonoids and mammalian lignans was substantially lower in breast cancer cases than in controls. The median excretion rate of total isoflavonoids was 13.97 nmol/mg creatinine in cases and 23.09 in controls (P = 0.01), and the median excretion rate of total lignans was 1.77 in cases and 4.16 in controls (P < 0.01). The risk of breast cancer was reduced with increasing excretion of total isoflavonoids (P for trend, 0.04) and total lignans (P for trend, <0.01), with adjusted odds ratios of 0.62 (95% confidence interval, 0.39-0.99) and 0.40 (95% confidence interval, 0.24-0.64) observed for the highest versus the lowest tertile of total isoflavonoid and lignan excretion, respectively. The adjusted odds ratio was 0.28 (95% confidence interval, 0.15-0.50) for women who had a high excretion rate of both total lignans and isoflavonoids compared with those with a low excretion of both groups of phytoestrogens. No association was observed with citrus flavonoids. The results from this study suggest that high intake of certain phytoestrogens may reduce the risk of breast cancer.

Adult↗

Changes in circadian sodium excretion in patients with essential hypertension and with renal artery stenosis.

In groups of healthy volunteers (C), patients with essential hypertension (EH), and patients with renal arterial stenosis (S), the following indicators were followed during 12-hour daytime (d) and nighttime (n) intervals: mean BP, endogenous creatinine clearance Ccr (GF), excretion of sodium (UNaV) and potassium (UKV), and their excretion fractions (CNa/GF and CK/GF). The d/n ratios of both UNaV and CNa/GF were significantly lowered in both groups of hypertensive persons as against the controls (1.5): in the EH, to 1.1, and in the S, to 0.8 on the average. Positively correlated with the value of the d/n ratio of the sodium excretion are the changes in the d/n ratios of water and solute excretions. The daytime potassium excretion exceeded the nighttime values in both groups of hypertensive persons. The d/n ratios of UKV and CK/GF were, however, significantly lowered as compared to the control values. These signs of disturbances of the circadian excretion of Na and K in EH and S exhibited no correlations with the values, or rhythms, of the mean BP, GF, or dietary uptake of sodium. The results do not indicate that the antihypertensive drugs used (alpha-methyldopa, dihydralazine, reserpine) would influence the circadian rhythm of Na excretion. The factors responsible for the disturbances of the circadian rhythms of Na and K excretion in hypertensive subjects have not yet been revealed.

Adult↗

Effects of ethinyl estradiol and phenobarbital on bile acid synthesis and biliary bile acid and cholesterol excretion.

Bile acid synthesis calculated from respiratory (14)CO2 derived from the catabolism of [26 or 27-(14)C]cholesterol to bile acids in rats with intact enterohepatic circulations decreased 50% after 5 days of ethinyl estradiol treatment (5 mg per kg per day). Maximal derepressed bile acid synthesis, measured as biliary bile acid excretion after bile acid pool depletion, was also reduced 50% by ethinyl estradiol treatment. Because ethinyl estradiol did not alter biliary cholesterol excretion, bile contained less bile acid relative to cholesterol. Hepatic bile acid concentration was not increased by ethinyl estradiol treatment. Because the inhibitory effect of ethinyl estradiol on bile acid synthesis required 5 days of treatment it is concluded that bile acid synthesis probably was not reduced by negative feedback repression of 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis, which has a half-life of 2 to 3 hr. During the first 14 hr after bile duct cannulation, before bile acid pool depletion, ethinyl estradiol-treated rats excreted less than one-half as much bile acid and the same amount of cholesterol as controls. The bile acid to cholesterol ratio was therefore decreased. Rats treated simultaneously with phenobarbital and ethinyl estradiol excreted significantly more bile acid than rats treated with ethinyl estradiol alone, but biliary cholesterol excretion was not increased. The proportion of biliary bile acid relative to cholesterol was thereby restored to the control value. In contrast, after 14 hr of bile drainage and depletion of the bile acid pool, rats treated with ethinyl estradiol and those treated with phenobarbital-ethinyl estradiol excreted the same amount of bile acid. Thus, when phenobarbital is administered with ethinyl estradiol, it increases the bile acid pool size and biliary bile acid excretion, but it does not increase bile acid synthesis. The increase in pool size and biliary bile acid excretion might be due to the phenobarbital-induced increase in ileal absorption of bile acids.

Animals↗

Biliary amino acid excretion in rats before and after bilateral nephrectomy.

In previous studies it could be shown that after bilateral nephrectomy (NX) the excretory function of the liver is disturbed. To further clarify whether or not this "renohepatic syndrome" is caused by toxic effects of uremia or by competition phenomena between various uraemic toxins an additional aspect was investigated: the biliary excretion of endogenous amino acids. Furthermore, previously it could be shown that renal and hepatic excretory functions overlap. Therefore, the renal excretion of effectively biliary eliminated amino acids (glutamic acid, alanine, tyrosine, isoleucine) is very low and vice versa. That means, that the renal excretion of amino acids with low hepatic elimination (tryptophan, citrulline, lysine, taurine) dominates. The hepatic excretion of amino acids is hardly altered after NX. Remarkably, the removal of both kidneys is followed by a distinct reduction in amino acid plasma concentrations, especially if these concentrations are relatively high in the controls. Interestingly, there is no correlation between plasma concentrations and biliary excretion of amino acids. But the calculation of the bile to plasma concentration ratios of amino acids makes it possible to differentiate three groups of amino acids: Amino acids excreted actively into bile (ratio > or = 1), amino acids with ratios below 1, indicating effective retention, and amino acids with ratios of about 1, whose hepatic handling is passive. After NX these ratios tended to approach 1; low ratios increased and high ratios decreased. That means, active processes involved in excretion or retention are obviously disturbed. These changes could indicate uraemic liver damage as proved regarding influence of NX on hepatic excretion of other endogenous substances and xenobiotics.

Amino Acids↗

[Urinary excretion of calcium, uric acid and citrate in healthy children and adolescents].

OBJECTIVE: To obtain regional reference values for calcium, uric acid and citrate urinary excretion and establish a correlation between those excretions in 24-hour urine sample and single urine sample for their use in clinical practice. METHODS: A hundred and twenty-five healthy children and adolescents were randomly chosen and submitted to the following protocol: clinical examination, biochemical analysis of blood, blood cell count, parathormone, 24-hour urine, fasting urine sample and stool test. RESULTS: The maximum value of calcium excretion in 24-hour urine was 3.75 mg/kg; in mg/dl of the glomerular filtration rate, it was 0.10; and for the calcium/creatinine (mg/dl) ratio in the fasting urine sample was 0.25. Positive correlation was observed between calcium excretion in the 24-hour urine and the fasting sample (mg/dl and mg/dl of glomerular filtration rate). The maximum values of uric acid excretion in 24-hour urine were 600, 450, and 320 mg and 13, 15 and 18 mg/kg for adolescents, school and preschool children, respectively; in mg/dl of glomerular filtration rate, in the fasting urine sample, it was 0.47. Positive correlation was observed for the uric acid excretion in 24-hour urine and fasting urine samples. The mean values for the citrate excretion in 24-hour urine were 1.6, 1.1 and 0.5 mmol for adolescents, school and preschool children, respectively; for citrate/creatinine ratio, in the fasting urine sample the mean value was 0.3. CONCLUSIONS: The calcium and uric acid excretion in 24-hour urine showed correlation with those in the fasting urine sample, which allows their use for metabolic diagnosis, population studies and follow-up of patients with hypercalciuria and hyperuricosuria without voiding control; the citrate/creatinine ratio in the fasting urine sample can be used for controlling patients with hypocitraturia.

English Abstract↗

[Effects of colchicine on synthesis and excretion of cytokines and extracellular matrix by human renal fibroblasts].

OBJECTIVE: Renal interstitial fibrosis is the final common pathway leading to end-stage renal failure for progressive renal disease of various types. The present study was undertaken to add to the knowledge on colchicine's antiinflammatory and antifibrotic properties confirmed by both human and experimental studies. As the main effector cells, fibroblasts have a central role in the pathogenesis of renal fibrosis. This study aimed to investigate the effects of colchicine on the synthesis and excretion of cytokines transforming growth factor-beta1 (TGF-beta1), interleukin-1beta (IL-1beta) and extracellular matrix (collagen III, collagen IV) in human renal fibroblast. METHODS: Various concentrations of colchicine (5.0 micromol/L, 10.0 micromol/L, 20.0 micromol/L, 40.0 micromol/L) were used to pretreat human embryo renal fibroblasts for 1 hour which were cultured in vitro and then stimulated by 10.0 microg/ml of lipopolysaccharide (LPS). After 18 hours, these fibroblasts and their supernatant were collected. The expression of TGF-beta1 mRNA, IL-1beta mRNA in the cells was studied by using RT-PCR, and the excretion of TGF-beta1, IL-1beta, collagen III and collagen IV by the fibroblasts was assessed by ELISA respectively. RESULTS: (1) By pure stimulation with 10.0 micro g/ml LPS, the expression of TGF-beta1 mRNA and IL-1beta mRNA of fibroblasts was up-regulated 3 times (66.1 +/- 1.6 vs. 22.3 +/- 2.0, q = 590.5, P = 0.002) and 4.7 times (22.0 +/- 2.2 vs. 4.7 +/- 0.8, q = 106.8, P = 0.009), respectively. The protein excretion of TGF-beta1 and IL-1beta was remarkably increased as well compared with the control group [TGF-beta1: (516 +/- 14) pg/ml vs. (420 +/- 5) pg/ml (q = 80.3, P = 0.012), IL-1beta: (3.4 +/- 0.3) pg/ml vs. (0.3 +/- 0.1) pg/ml (q = 297.9, P = 0.003)]. (2) Colchicine could inhibit the expression of TGF-beta1 mRNA and protein in a dose-dependent manner. IL-1beta mRNA and protein were both up-regulated by colchicine. (3) LPS could not stimulate the excretion of extracellular matrix by fibroblasts, but the excretion of collagen III and collagen IV was down regulated by colchicine in a dose-dependent manner. CONCLUSION: (1) The expression of TGF-beta1 mRNA and the excretion of TGF-beta1 protein in the fibroblasts was significantly suppressed by colchicine, while the expression of IL-1beta mRNA and the excretion of IL-1beta protein were enhanced. (2) Colchicine has significant inhibitory effect on the excretion of extracellular matrix such as collagen III and collagen IV in fibroblasts.

Colchicine↗

[Prognostic values of serum concentration and urinary excretion of interleukin-1 receptor antagonist and tumor necrosis factor receptors type I and II in patients with IGA nephropathy].

Interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor soluble receptors (sTNFR) type I and II reducing the activity of IL-1 and TNFalpha may inhibit inflammatory reactions. The aim of the study was to assess whether serum and urine IL-1ra and sTNFR measurements may be useful as the early predicting factors in patients with IgA nephropathy. Twenty seven patients (16 males, 11 females), mean age 41.6 +/- 22.3 years with biopsy-proven IgA nephropathy and nephrotic-range proteinuria were included in this study. Serum concentrations (sIL-1ra, ssTNFR I and II) and urinary excretions (uIL-1ra, usTNFR I and II) of IL-1ra, sTNFR I and II had been measured before the treatment was instituted. After 12 months of therapy with steroids and cyclophosphamide, the patients were divided into two subgroups i.e. R - responders, and NR - nonresponders according to the treatment results. The control groups comprised 8 healthy people. IL-1ra serum concentration and urinary excretion were lower in the patients than in the controls (202 vs 330 ng/ml and 970 vs 1607 ng/mg creatinine respectively; p < 0.05 both). Serum concentrations and urinary excretion rates of sTNFR 1 (5.1 vs 1.7 ng/ml and 4.1 vs 1.1 ng/mg creatinine respectively) and sTNFR II (14.4 vs. 5.0 ng/ml and 8.3 vs. 4.4 ng/mg creatinine respectively) were higher (p < 0.05 each) in the patients than in the controls. The subdivision of patients and their classification according to achieved treatment results showed no statistically significant differences between initial interstitium volume neither concentration of serum total protein, serum creatinine or proteinuria and glomerular filtration rate in R and NR subgroups. Initial IL-1ra serum concentration, its urinary excretion and sTNFR type I and II urinary excretion rates were significantly higher in R than NR (sIL-1ra - 297 vs 167 ng/ml, p < 0.05; uIL-1ra 1360 vs 87 ng/mg Cr, p < 0.01; and ssTNFR I 5.2 vs 2.2 ng/mg Cr, p < 0.05; ssTNF RII14 vs 6 ng/mg Cr, p < 0.05). However, serum concentration and urinary excretion of sTNF R type I and II were significantly higher in R and NR subgroups than in controls (p < 0.05 both), sIL-1ra and uIL-1ra were significantly lower in R and NR than in healthy subjects. The results of evaluations of serum concentration and urinary excretion of IL-1ra showed similar values to control group results only in responders. No statistically significant differences between sIL-1ra or/and uIL-1ra in both R and control groups were found. Increased serum concentration and urinary excretion of IL-1ra correlates with better prognosis for remission of proteinuria and lower risk of deterioration of kidney function. Those assessments may be helpful as a part of initial screening in patients with IgA nephritis and heavy proteinuria. In contrast the evaluation of both serum and urinary TNF RI and II seems to have no predictive value.

Adult↗

Magnesium urinary excretion in diabetic adolescents.

OBJECTIVE: To define peculiarities of urinary magnesium (Mg) excretion in diabetic adolecents; to elucidate gender-related differences in Mg urinary excretion; to determine urinary Mg excretion differences between diabetic and age-matched healthy children. The diurnal, nocturnal and 24-h urinary Mg level in adolescent boys and girls (aged 13-17 years) with type I diabetes mellitus (DM) and in age-matched control groups of healthy boys and girls was examined. Additionally the adolescent girls were examined during different phases of their menstrual cycle. RESULTS: Diurnal, overnight and 24-h Mg urinary excretion in diabetic adolescent boys and girls was significantly higher than in healthy ones. In diabetic boys 24 h Mg excretion was higher than in diabetic girls (4.59 +/- 1.4 vs. 3.34 +/- 1.5 mmol; p < 0.05). The investigation showed gender-related differences in Mg urinary excretion in healthy adolescents: 24-h Mg urinary excretion was significantly higher in boys than in girls (2.66 +/- 0.9 vs. 2.1 +/- 0.9 mmol; p < 0.05). The level of Mg in the nocturnal urine of boys and girls was significantly higher than in diurnal. Urine Mg was negatively related to height in adolescent girls. CONCLUSION: Diabetic adolescents excrete significantly more Mg with urine as compared to healthy ones.

Adolescent↗

Urinary protein excretion in children from families with Balkan nephropathy.

We studied the urinary excretion of total protein and five other proteins in urine samples from a total of 831 children and adolescents. The characteristics of the children were: (1.) they resided in areas where Balkan nephropathy (BEN) is endemic and also had family members suffering from BEN; (2.) they resided in areas where BEN is endemic, but the families had no members suffering from the disease; (3.) they lived in nonendemic settlements; (4.) they lived in the city of Nis. Urinary excretion of total protein (TP), albumin (ALB), alpha 2-macroglobulin (alpha 2m), transferrin (TF), IgG, and beta 2-microglobulin (beta 2m) were measured. This study showed that urinary excretion of beta 2m and albumin in children from endemic settlements and from families affected with Balkan nephropathy were not different from the control rural settlements. However, children residing in the city of Nis had significantly increased urinary beta 2m and albumin excretion, over 1.5 to 2.6 times the excretion in the other three groups, although excretion of either protein remained within accepted normal ranges in all groups. The increased excretion of beta 2m and albumin in children from the city of Nis could probably be related to the different growth conditions and/or the effect of toxic environmental factors. These data could serve as a reference base for future comparative studies of urinary protein excretion in children as well as in BEN populations.

Adolescent↗

Relationship between urine ammonium ion excretion and urine anion gap in dogs.

Acidemia stimulates renal ammonia production and excretion. This adaptive response allows increased H+ secretion and generation of new bicarbonate. To determine whether a relationship existed between urine ammonium (NH4+) concentration and excretion and urine anion gap (Na+ + K(+)- Cl-), ammonium chloride (NH4Cl) was administered per OS for 5 days to induce systemic acidemia in 12 healthy Beagles. During NH4Cl administration, a strong, statistically significant (P less than 0.0001) relationship was apparent between urine NH4+ concentration measured in millimoles per liter and urine anion gap. Regression equation: urine [NH4+] = 8.2 - 0.416 x urine anion gap; r = -0.897. A statistically significant (P = 0.0001) relationship existed between urine NH4+ excretion measured in millimoles per kilogram of body weight per day and urine anion gap. Regression equation: urine NH4+ excretion = 0.74 - 0.38 x urine anion gap; r = -0.768. As urine NH4+ concentration or excretion increased, urine anion gap became more negative. Before NH4Cl administration (no systemic acidemia), a weak, but statistically significant (P = 0.015) relationship was observed between urine NH4+ concentration and urine anion gap. Regression equation: urine [NH4+] = 65.2 - 0.141 x urine anion gap; r = -0.41. However, a relationship was not evident between urine NH4+ excretion and urine anion gap before NH4Cl administration. Hence, urine anion gap is a reliable index of urine NH4+ concentration and excretion only in dogs with metabolic acidosis. In human beings with distal renal tubular acidosis, NH4+ excretion is inappropriately low and results in a positive urine anion gap.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Decreased urinary excretion of dopamine and sodium in diabetic children with incipient nephropathy.

It has been suggested previously that a decrease in urinary dopamine output might be related to a decrease in the urinary sodium excretion in subjects with diabetic nephropathy suffering from type 2 diabetes. To investigate the renal dopamine status in children with type 1 (insulin-dependent) diabetes mellitus, we measured the 24-hour urinary excretion of dopamine, norepinephrine and sodium in 12 patients with incipient nephropathy (group A, 24-hour albumin excretion rate 70-200 micrograms/min), in 20 age matched patients with normal microalbuminuria (group B, AER less than 20 micrograms/min) and in 8 healthy controls (group C). The mean values for urinary excretion of dopamine and norepinephrine were significantly lower in group A compared to groups B and C (25.6 +/- 14.8 vs. 65.9 +/- 25.5 and 73.3 +/- 18.0 micrograms/day, p less than 0.001 and 11.8 +/- 4.6 vs. 25.1 +/- 12.1 and 28.4 +/- 8.9 micrograms/day, p less than 0.01, respectively). The mean value for the urinary excretion of sodium was also significantly lower in group A than in groups B and C (98.4 +/- 24.1 vs. 206.2 +/- 59.5 and 198.1 +/- 42.8 mEq/day, p less than 0.01). The 24-hour urinary excretion of dopamine correlated significantly with the sodium excretion (r = 0.65, p less than 0.001). Arterial blood pressure was elevated in group A compared to group C (p less than 0.01). Our results suggest that a decrease in endogenous dopamine could play a role in the low urinary sodium excretion thereby resulting in sodium retention which may in turn lead to the development of higher blood pressure in diabetic children with incipient nephropathy.

Adolescent↗

Postnatal development of urea- and ammonia-excretion in urine of very-low-birth-weight infants small for gestational age.

In 12 very-low-birth-weight (VLBW) infants with intrauterine growth retardation and in 14 VLBW-infants appropriate for gestational age (AGA) fed a human milk (HM) formula (HM enriched with 6 g freeze dried HM per 100 ml) the renal excretion of urea and ammonia was studied on the 10th, 21st and 42nd days of life. The lowest excretion of urea was found in both groups on the 10th day of life. Up to the 42nd day of life the excretion raised significantly more in the AGA- than in the small for gestational age (SGA)-infants. In contrast to the urea excretion the excretion of ammonia was highest on the 10th day of life in both groups, but the excretion was significantly higher in the SGA-infants if compared to the AGA-infants. In the AGA-infants excretion of ammonia decreased with postnatal age whereas in the SGA-infants the high excretion remained up to the 42nd day of life. The data suggest that in VLBW-infants the urea synthesizing capacity is decreased and develops within the first weeks of postnatal life. The postnatal development is delayed in SGA-infants when compared to AGA-infants. The differences are more pronounced with increasing degree of intrauterine growth retardation.

Ammonia↗

[Daily periods of aldosterone, sodium, and potassium excretion in the urine of newborns, infants, and children: influence of long-term steroid treatment and of the blockage of adrenergic beta-receptors (author's transl)].

Aldosterone, sodium, and potassium excretion in the urine of six newborns (5, 6, and 9 days), seven infants (2, 3, 4, and 6 months) and eight children (4, 5, 6, 12, and 15 years) was determined at 3-hour intervals during a 24-hour period via gas chromatography and/or flame photometry. The circadian rhythmn of aldosterone excretion could already be ascertained in the 5-day-old newborns. All babies and children examined showed a distinct increase in aldosterone excretion between 3 and 6 am or 6 and 9 am. On the overage, 41% of the total daily amount was excreted between 3 and 9 am. Excretion of sodium and potassium was very low for the newborns and infants. Only in small children and in school children did sodium excretion and the molecular relationship Na/k in urine have a statistically significant negative correlation with the excretion of aldosterone. After long-term prednisone therapy, the maximum amount of aldosterone was excreted in the afternoon. The findings after treatment with propranolol and administration of dexamethasone over a three-day period were similar.

Adolescent↗

Low-molecular-weight proteinuria in insulin-dependent diabetes mellitus: a study of the urinary excretion of beta 2-microglobulin and retinol-binding protein in alkalinized patients with and without microalbuminuria.

The urinary excretion of two low-molecular-weight proteins (beta 2-microglobulin and retinol-binding protein) was measured in 12 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with normal albumin excretion; reference ranges for the excretion of beta 2-microglobulin (beta 2M) and retinol-binding protein (RBP) were also obtained in 40 non-diabetic subjects. To ensure the stability of beta 2M in urine a urinary pH greater than or equal to 7 was achieved by giving oral sodium bicarbonate. beta 2M and RBP excretion was significantly higher in the diabetics than in the controls (p less than 0.01), but no higher in microalbuminuric than non-albuminuric diabetics. In the diabetics as a group a significant correlation was found between the excretion of beta 2M and RBP (r = 0.53, p less than 0.01), but more patients had an abnormal excretion of beta 2M than RBP (p less than 0.001). No significant correlation was found between the urinary excretion of either low-molecular-weight protein and duration of diabetes, insulin dose, HbA1, urinary glucose excretion or systemic blood pressure. Measured under appropriate alkaline conditions beta 2M appears to be more sensitive than RBP in detecting an abnormality of the renal proximal tubule which may be an early feature of diabetic renal involvement not characterized by microalbuminuria; microalbuminuria may have glomerular and tubular components.

Adolescent↗

Biliary excretion of acetaminophen-glutathione as an index of toxic activation of acetaminophen: effect of chemicals that alter acetaminophen hepatotoxicity.

Acetaminophen (AA) is converted, presumably by cytochrome P-450, to an electrophile which is conjugated with glutathione (GS). AA-GS is excreted into bile, therefore the biliary excretion rate of AA-GS may reflect the rate of activation of AA in vivo. In order to test this hypothesis, the effect of agents capable of altering the activation of AA including cytochrome P-450 inducers and inhibitors, cobaltous chloride which decreases the amount of P-450, prostaglandin synthetase inhibitors (indomethacin and naproxen), antioxidants (butylated hydroxyanisole, alpha-tocopherol, ascorbic acid and ascorbic acid palmitate) and other chemicals known to decrease AA hepatotoxicity (dimethylsulfoxide and cysteamine), on the biliary excretion of AA-GS was studied in hamsters, the species most sensitive to AA-induced hepatotoxicity. The biliary excretion of AA-GS increased linearly up to 1 mmol/kg of AA i.v., but at higher dosages exhibited saturation kinetics. Dosages above 0.5 mmol/kg lowered hepatic GS concentration. Of the cytochrome P-450 inducers, 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin, increased the biliary excretion of AA-GS (2.9- and 3.2-fold, respectively) whereas ethanol and isoniazid did not affect it, and pregnenolone-16 alpha-carbonitrile tended to decrease it (43%). Phenobarbital tended to increase the biliary excretion of AA-GS, but not in a statistically significant manner. Several cytochrome P-450 inhibitors [metyrapone, 8-methoxypsoralen, 2-(4,6-dichloro-biphenyloxy) ethylamine, alpha-naphthoflavone and cimetidine] decreased the biliary excretion of AA-GS, although SKF 525-A and piperonyl butoxide did not. Cobaltous chloride decreased dramatically the biliary excretion of AA-GS.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Urinary excretion of 3-methylhistidine, creatinine and total nitrogen by Kenyan children during acute measles and after recovery.

The urinary excretion of 3-methylhistidine (3MH), creatinine and total nitrogen was measured during the course of energy balance studies on 20 black Kenyan children. Studies were carried out over 24 h during an acute attack of measles with a second (control) study after recovery, and complete urinary collections were obtained on 14 ill and 18 recovered children. The nutritional status was assessed by anthropometry, and energy intake was determined by duplicate diet analysis. Twelve out of 13 acutely ill and 6 out of 17 recovered children were in negative energy balance. No effect on the rate of excretion of 3MH or of creatinine attributable to differences in nutritional status, of energy intake or to infection was observed. The linear relationship between the excretion rate of all three metabolites and body weight which was observed in recovered children was absent during acute infection. Nitrogen excretion was correlated (P less than 0.05) with the level of energy intake. The linear relationship between the rate of excretion of 3MH and creatinine and of 3MH and nitrogen was significantly closer in recovered than in ill children. The simultaneous effects of infection, underfeeding (and oliguria) on the rate of excretion of protein metabolites may be complex and contradictory. Our results suggest that the excretion of 3MH, creatinine and nitrogen is sustained during infection accompanied by negative energy balance. Disruption during infection of the relationship between the excretion of all three metabolites and body weight, and between 3MH and the other two metabolites suggests perturbation in protein metabolism at this time.

Child, Preschool↗