Nitric oxide modulation of erythropoiesis in rats.
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Biomedical subjects
Publications and source records attributed to H Tsukahara.
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We measured urinary nitrite/nitrate (NOx-) excretion, an index of endogenous nitric oxide formation, in term and preterm infants aged 1 week and 1, 4, 7 months. In normal term infants, urinary NOx excretion increased from 1 week to 1 month and then decreased until 4 months where it stabilized thereafter. Urinary NOx- excretion in preterm infants was significantly higher compared with term infants at 1 week of age. This finding suggests that the nitric oxide pathway in preterm infants may be activated compared with term infants in early life. With the reference values obtained in this study, this urinary marker can now be used for identifying infants with abnormal nitric oxide production.
The present study investigated whether ultrasonography was effective in detecting ureteric reflux in children suspected of having urinary infection. Seventeen children with febrile episodes and pyuria were enrolled. The ultrasound examination revealed ballooning of the renal pelvis during bladder contraction in 4 children, dilatation of the distal ureters in 6, and small kidney in 2. Cystography was performed on the 6 children with these ultrasound abnormalities and 1 child with two episodes of suspected urinary infection. Four children showed reflux. All of the 4 children had been found to have renal pelvic ballooning on ultrasound. None of the 10 children who did not undergo cystography had recurrence of urinary infection or significant bacteriuria during a median follow-up period of 12 months. Thus, scanning during bladder contraction was effective in detecting significant ureteric reflux.
The effectiveness of intermittent low-dose trimethoprim-sulfamethoxazole (TMP-SMZ) for the prophylaxis of recurrent urinary infection is well established in adults. The present study assessed the effectiveness and safety of intermittent low-dose TMP-SMZ in 35 children (24 boys, 11 girls, aged 1 month to 9 years, median age 5 months) with vesicoureteral reflux; 18 children had bilateral reflux. A total of 53 refluxing ureters were graded as I in 2, II in 16, III in 19, IV in 14, and V in 2 cases. The children were given 1 mg/kg body weight of trimethoprim together with 5 mg/kg of sulfamethoxazole at bedtime every other day for 6-50 months (mean +/- SD, 22.9 +/- 11.7 months). None of the boys had a recurrence of urinary infection, while 2 of the 11 girls had a total of 7 recurrences during the prophylaxis period, with a recurrence rate of 0.027 per patient month in girls. Both girls were over 3 years and had a mildly unstable bladder. Transient neutropenia (< 1,000/microliter) developed in 2 infants during the prophylaxis period, but disappeared spontaneously. Intermittent low-dose TMP-SMZ seemed very effective for the prevention of recurrent urinary infection in children with ureteral reflux even of higher grades.
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Insulin-mediated glucose metabolism in skeletal muscle is associated with a proportional increase in muscle perfusion. The vasodilatory effect of insulin is thought to be mediated in part by endothelium-derived nitric oxide (NO). The present study was performed to determine whether acute hyperinsulinemia has any stimulatory effect on endogenous NO production in humans. Bolus intravenous injection of insulin (0.1 IU/kg body weight) caused a significant increase in urinary excretion of NO2-/NO3- together with a significant decrease in blood pressure, whereas saline infusion alone had no effect on these parameters. The increased NO response to insulin was almost comparable to that obtained with infusion of 30 g L-arginine. The acute effect of hyperinsulinemia on endogenous NO formation supports the concept that NO may mediate the vasodilatory action of insulin in humans.
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We measured the urinary excretion of nitrite/nitrate, stable metabolites of nitric oxide, using the brucine method in 90 healthy normal children (47 boys and 43 girls), aged from 1.0 to 17.1 years, to establish the age-related normal range in children. The urinary nitrite/nitrate excretion was highest in the youngest children and decreased in an age-dependent manner to reach constant levels at about 12 years of age in both sexes. The data may be useful in identifying sick children with abnormal nitric oxide production.
To evaluate in vivo nitric oxide production in Kawasaki disease (KD), urinary nitrite/nitrate (NOx) excretion was measured in 8 children with KD (age 1.1-2.7 years). Urinary NOx excretion was 0.66 +/- 0.22 mmol mmol-1 creatinine (mean +/- SD) in the 8 children with KD in the initial stages. The levels were significantly increased compared with those of 12 age-matched healthy control subjects (0.35 +/- 0.08 mmol mmol-1 creatinine). Urinary Nox excretion was serially determined in four patients. For each patient, there was a further rise in urinary NOx excretion from baseline levels coincident with the administration of intact-type gammaglobulin and aspirin. With clinical and laboratory improvement, however, urinary NOx excretion declined to the normal range. These findings suggest that endogenous nitric oxide production is enhanced in children with acute KD. Further studies are needed to clarify the role of nitric oxide in the pathogenesis and clinical course of KD.
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This cross-sectional study evaluated urinary excretion of pyridinium cross-links of collagen, specific markers of ongoing bone resorption, in infants aged 1 week to 7 months and examined the relationship between urinary cross-links and individual renal function. Spot urines from a total of 100 infants were analyzed. The collagen cross-links, pyridinoline (Pyd) and deoxypyridinoline (D-Pyd), were assayed by fluorescence detection after high-performance liquid chromatography (HPLC). Beta2-Microglobulin (beta2M), an index of renal tubular function, was determined by radioimmunoassay. In healthy term infants, urinary collagen cross-links were several times higher than the reported data for older children, with peak values seen at 1 month of age. Excretion of Pyd and D-Pyd was also markedly elevated in 1-month-old preterm infants, despite poor somatic growth. Such high excretion of collagen cross-links probably reflects the state of accelerated bone turnover in infancy. The postnatal change in the cross-links was different from that in urinary beta2M, and the values obtained did not correlate with beta2M in either term or preterm infants. These results indicate that cross-link excretion is not influenced directly by individual renal function.
OBJECTIVE: To clarify postnatal changes in urinary uric acid (UA) excretion in normal term infants and to examine the effects of prematurity or illness on the UA excretion. METHODOLOGY: Measurements of urinary UA were performed in term and premature infants at the ages of 1 and 7 days and at 1 and 4 months, as well as 7 months in term infants. RESULTS: Urinary UA levels were lowest on day 7 in term infants. The levels were highest on day 1 in premature infants and remained significantly higher compared to term babies during the first month of life. Respiratory failure requiring ventilation and oxygen supply resulted in further significant elevation of urinary UA in premature infants. CONCLUSIONS: With the reference values obtained in the study reported here, urinary UA can now be used for the diagnosis and monitoring of inherited disorders of purine metabolism and for the assessment of oxygen radical insult to sick infants.
Several less harmful methods than voiding cysto-urethrography for detecting significant ureteric reflux have been proposed. The present prospective study investigated whether ultrasonography was effective in identifying ureteric reflux in infants with their first febrile urinary infection. The subjects were 27 infants (24 boys and 3 girls) aged from 0 to 8 months. The urinary tract was scanned when the bladder was full, and before and during induced voiding. Infants with abnormal ultrasound findings underwent voiding cysto-urethrography. The other infants were followed and those who had a recurrence of urinary infection underwent voiding cystography. Ten children underwent cysto-urethrography, with eight refluxing ureters identified in six boys. Ultrasound revealed transient dilatation of the renal pelvis on voiding in five kidneys, transient dilatation of distal ureters in 12 and hydro-ureteronephrosis in two. Each of the five kidneys with pelvic dilatation on voiding was associated with ureteric reflux grades III or IV. Of the 17 children who did not undergo cysto-urethrography, only one had recurrence of urinary infection and was diagnosed with ureteric reflux. This girl was one of the three babies who were not scanned during voiding. More than half of the infants with febrile urinary infection were excluded from invasive examination without having recurrence of urinary infection. Thus, ultrasound scanning during voiding was effective for screening infants with their first urinary infection to detect significant ureteric reflux.
Reflux nephropathy is known to be a major cause of renal failure in children. Vesico-ureteral reflux is usually diagnosed by voiding cysto-urethrography (VCG). However, it has been observed that conventional VCG is not always reliable for the diagnosis of ureteral reflux. In the case of a 5 year old girl with recurrent febrile urinary tract infection, VCG showed no ureteral reflux. Urodynamic study revealed a large bladder capacity and significant residual urine. Renal scintigram delineated a right renal scar. Simple ultrasound examination with videotape recording during voiding definitely demonstrated the presence of significant ureteral reflux when she voided, that is, there was marked dilatation of the right distal ureter and ballooning of the right renal pelvis on voiding, and quick refilling of the bladder concomitantly with the disappearance of the pelvic ballooning. Therefore, an ultrasound during voiding may be useful for diagnosing ureteral reflux in patients where a VCG does not reveal reflux.
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The purpose of the present study was to examine renal functional changes caused by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO synthase inhibitor were used: NG-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20-80 mg/dL of drinking water), not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated rats. Both inhibitors caused a significant reduction in urinary excretion of NO2-/NO3-. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high excretion of N-acetyl-beta-D-glucosaminidase) in a dose-dependent fashion, with normal serum levels of creatinine, albumin and cholesterol. Chronic AG administration did not alter the urinary levels of protein and N-acetyl-beta-D-glucosaminidase or serum laboratory values. Overall, these observations highlight the importance of the continuous generation of NO by the constitutive isoform in the control of vascular tone and the maintenance of renal glomerular and tubular function. Oral administration of L-NAME may serve as a model of chronic NO-deficient hypertension with renal injury in young rats.