The role of histidine in the anemia of folate deficiency

The amino acid histidine is metabolized to glutamic acid in mammalian tissue. Formiminoglutamic acid (FIGLU) is an intermediary in this reaction, and tetrahydrofolic acid is the coenzyme that converts it to glutamic acid. A test for folate deficiency concerns the measurement of urinary FIGLU excretion after a histidine load. It was observed that folate-deficient individuals receiving the histidine for the FIGLU test made hematological response that alleviated the anemia associated with this deficiency. This was unusual in that a biochemical test to determine the deficiency results in a beneficial effect for one aspect of the deficiency. The studies reported in this paper give a metabolic explanation for this phenomenon. Urine was collected for 24 hr from 25 folate-deficient subjects, 10 vitamin B(12)-deficient subjects, and 15 normal controls. Urinary excretion of histidine was a mean of 203 mg with a range of 130-360 mg for the folate-deficient subjects; 51.5 mg with a range of 30-76.6 mg for normal subjects; and 60.0 mg with a range of 32.3-93.0 mg for the vitamin B(12)-deficient subjects. All the folate-deficient subjects subsequently made a hematological response to the histidine administered for the FIGLU test. No hematological response was observed in the vitamin B(12)-deficient individuals. When folic acid was given to folate-deficient subjects who received no histidine, urinary histidine levels returned to normal levels rapidly and this was followed by a hematological response. Others have shown that volunteers fed a histidine-free diet developed anemia. In normal subjects, histidine is excreted much more in the urine than other essential amino acids are. Hemoglobin protein contains 10% histidine. Under normal conditions, dietary histidine can supply sufficient histidine to prevent anemia. When the dietary intake is diminished or the urinary excretion is greatly increased, anemia results. It is concluded that folate deficiency causes histidine depletion through increased urinary excretion of this amino acid. Feeding histidine replenishes tissue levels of histidine, resulting in hemoglobin regeneration. Folic acid administration results in return of histidine to normal urinary levels. Thus, a combination of folic acid histidine would be beneficial for folate deficient individuals.     

Urinary selenium and iodine during pregnancy and lactation

The New Zealand environment is low in selenium and iodine, and is therefore ideally suited for the study of these anionic trace elements. The aim of this study was to determine urinary excretion of selenium and iodine during pregnancy and postpartum as part of an investigation of the influence of pregnancy and lactation on selenium metabolism in women of low selenium status. In a double-blind placebo-controlled study, 35 women in the earliest stages of pregnancy and 17 non-pregnant women were recruited in Dunedin, New Zealand. Eighteen pregnant women received 50 μg selenium as L-selenomethionine, while the others received a placebo daily during pregnancy and 12 months postpartum. The non-pregnant women received the supplement, serving as a positive control. Blood samples and twenty-four hour urine samples were collected monthly during pregnancy and at 3, 6, and 12 months postpartum for analysis of selenium and iodine. Selenium content in plasma and urinary excretion of selenium fell during pregnancy; however, total excretion of selenium was greater during pregnancy than postpartum. Urinary iodine excretion was much lower than reported previously in New Zealand. Due to large intra- and inter-subject variability, no trends in iodide excretion were observed. Factors which influence urinary excretion of selenium include dietary intake, but more closely, plasma concentrations of selenium (which is probably related to total selenium pool), creatinine excretion and therefore lean body mass, and glomerular filtration rate. The exact mechanism and sequence of events remains unclear and future studies incorporating new speciation techniques are necessary.     

Serum Gamma - Glutamyltransferase Is Associated with Albuminuria: A Population-Based Study

Background

Serum γ - glutamyltransferase (GGT) is implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Albuminuria is a marker of endothelial damage and correlated with structural and functional integrity of the vasculature. Our objective was to evaluate the association between serum GGT level and prevalence of albuminuria in a Chinese population.

Materials and Methods

We conducted a population-based cross-sectional study in 9,702 subjects aged 40 years or older. Increased urinary albumin excretion was defined according to the urinary albumin-to-creatinine ratio (ACR) ranges greater or equal than 30 mg/g. Low-grade albuminuria was defined according to the highest quartile of ACR in participants without increased urinary albumin excretion.

Results

The prevalence of low-grade albuminuria and increased urinary albumin excretion were respectively 23.4% and 6.6% in this population and gradually increased across the sex-specific serum GGT quartiles (all P for trend <0.05). In logistic regression analysis, compared with subjects in the lowest quartile of serum GGT level, the adjusted odds ratios (ORs) in the highest quartile was 1.22 [95% confidence interval (CI), 1.04–1.43] for low-grade albuminuria and 1.55 (95% CI, 1.18–2.04) for increased urinary albumin excretion. In subgroup analysis, significant relationship of serum GGT level with both low-grade albuminuria and increased urinary albumin excretion were detected in women, younger subjects, overweight subjects and in those with hypertension or glomerular filtration rate greater than 90 (all P <0.05).

Conclusion

Serum GGT level is associated with urinary albumin excretion in middle-aged and elderly Chinese.     

Nanoselenium Supplementation of Heat-Stressed Broilers: Effects on Performance,Carcass Characteristics,Blood Metabolites,Immune Response,Antioxidant Status,and Jejunal Morphology

Magnesium (Mg) is an essential nutrient as a structural constituent of bone and regulator of >300 enzymes. However, studies on intake and urinary excretion of Mg are limited. The purpose of this study was to evaluate Mg intake and its relation to 24-h urinary excretion in healthy adults. Anthropometric measurements and dietary intake by the 24-h recall method were conducted in 80 adults aged 21–69 (average 44.3) years. Urine was collected for 24 h on the day following the dietary survey. Dietary assessment and 24-h urine collection were repeated 3 days later. Daily intake and urinary excretion of Mg were analyzed using Can-Pro and ICP-OES, respectively. The statistical analysis was conducted using SAS program. Mg intake of the subjects was 319 ± 129 mg/day for men and 277 ± 94 mg/day for women and the proportion of subjects who did not meet the estimated average requirement was 50 and 67.5 % for men and women, respectively. Urinary Mg excretion was 30.3 % of the daily Mg intake. Urinary Mg excretion was not significantly correlated with the daily Mg intake. Korean adults are not meeting the recommended intake of Mg, but its urinary excretion suggests homeostasis is not compromised.     

Factors affecting formiminoglutamic acid excretion in vitamin B12 deficiency

1. Formiminoglutamic acid, a product of the catabolism of histidine, is excreted in abnormally large amounts in the urines of vitamin B(12)-deficient rats and of vitamin B(12)-deficient sheep; the excretion is reduced to negligible amounts after administration of vitamin B(12). 2. After administration of certain methyl donors to vitamin B(12)-deficient rats or sheep urinary excretion of formiminoglutamic acid is temporarily decreased. 3. Irrespective of the pteroylglutamic acid status of the animals neither vitamin B(12)-deficient rats nor vitamin B(12)-deficient sheep have the ability to deal efficiently with histidine. 4. In sheep, urinary excretion of formiminoglutamic acid is increased after administration of aminopterin; treatment with pteroylglutamic acid restores the ability of the animal to deal with the catabolic products of histidine. 5. The possible functions of vitamin B(12) and methionine in relieving a virtual deficiency of pteroylglutamic acid are discussed.     

Salt and blood pressure in Scotland.

Dietary salt intake and urinary sodium excretion were compared in normotensive and hypertensive subjects in Renfrew, Scotland. All groups had high 24-hour urinary salt excretions, and hypertensive subjects did not eat or excrete more salt than normotensive subjects. The only significant relations found were a lower sodium excretion in hypertensive women than in normotensive women (p < 0.02) and a lower urinary sodium concentration in hypertensive men than in normotensive men (p < 0.05). These data provide no support for the hypothesis that dietary salt is a major cause of hypertension.     

Excretion of non-conjugated androstenedione and testosterone in human urine.

A method for the measurement of unconjugated testosterone and androstenedione in human urine is described. The method uses chromatographic separation followed by radioimmunoassay and has been examined for reliability. The mean 24-hour excretion of androstenedione by adult male subjects was 2.5 mug and of testosterone was 0.8 mug. For women, the mean excretion was 2.9 mug of androstenedione and 0.25 mug of testosterone. In pregnancy, androstenedione excretion was occasionally elevated above the normal range, but testosterone excretion was quite commonly increased. Some hirsute subjects exhibited an increase in androstenedione excretion, which was decreased by administration of dexamethasone. The results suggest that the amount of unconjugated testosterone in urine is not a direct reflection of the plasma free testosterone, but urinary androstenedione may be a useful reflection of plasma androstenedione levels.     

Physiological effects of shift work on hospital nurses

OBJECTIVE: The purpose of this study was to assess the physiological effects of shift work on the urinary excretion rates of norepinephrine, 6-sulfatoxymelatonin and estriol in hospital nurses. METHOD: Twenty-four hour urine specimens were examined on a daytime/nighttime basis for each work shift of pregnant and non-pregnant subjects. The urinary norepinephrine and 6-sulfatoxymelatonin were measured by enzyme-linked immunosorbent assay and estriol by radio-immunoassay. RESULTS: Urinary norepinephrine level during the night work was higher than the night levels of the days off and the day shift. Urinary 6-sulfatoxymelatonin level during the night work was lower than the night levels of the days off and the day shift. Urinary estriol level of pregnant subjects showed no differences among work shift and also between daytime and nighttime. CONCLUSIONS: Urinary excretion rates of norepinephrine and 6-sulfatoxymelatonin were affected by shift work both for non-pregnant and pregnant subjects. It was unlikely that urinary estriol levels in the pregnant subjects were significantly affected by shift work.     

Mortality in a cadmium polluted area in Japan

A 15-year follow-up study of 3178 inhabitants (1424 men and 1754 women) living in the cadmium (Cd) polluted Kakehashi River basin was conducted. The results clarified effects on mortality of renal dysfunction induced by Cd indicated by urinary beta-2-microglobulin (beta2-MG), total protein, glucose, and total amino acids. This study used Cox's proportional hazard model. The mortality risk ratio of urinary beta2-MG positive (>= 1000 microg/gCr) subjects was significantly increased in both sexes: 1.35 for men and 1.73 for women. The increased mortality ratio of the urinary protein positive (>= 10 mg/dl) subjects was also significant for both sexes, with risk ratios of 1.82 for men and 2.01 for women. Only the women showed significantly increased mortality of the urinary glucose positive (>= 20 mg/dl) subjects and amino acids positive (> = 300 microg/gCr) subjects. When the subjects were divided into four categories according to urinary beta2-MG, <300, 300-1000, 1000-10000, >= 10000 microg/gCr, the mortality risk ratios were increased in proportion to the increase of urinary beta2-MG in both sexes. These results suggest that mortality of Cd-exposed subjects increased with increasing excretion of four urinary markers of renal tubular dysfunction, and in proportion to increases in the amount of urinary beta2-MG excretion including under 1000 microg/gCr.     

Increase in urinary thromboxane excretion during pregnancy and labor

Urinary TXB₂ excretion was measured during pregnancy and labor using high pressure liquid chromatography and radioimmunoassay. From the first trimester onwards TXB₂ levels in urine of pregnant women (n=60) were significantly (p <0.001) higher than in non-pregnant women (n=12) and they increased, albeit not significantly, with advancing gestation. Labor was associated with a two-fold increase in urinary TXB₂ excretion. Levels in established labor were significantly higher than at any other time in pregnancy (p <0.001), but the levels in incipient labor showed considerable overlap with these in late pregnancy. Thus urinary TXB₂, while not necessarily originating from the pregnant uterus, appears to reflect the uterine activity of labor and may be the expression of a general stimulation of prostanoid production during parturition.     

High levels of urinary vascular endothelial growth factor in women with severe preeclampsia

Elevated plasma VEGF concentrations in preeclampsia are associated with local placental ischemia and endothelial dysfunction. We investigated the urinary VEGF excretion in women with severe preeclampsia (n=37) and its relation with proteinuria compared to that in healthy pregnant (n=32) and non-pregnant women (n=30). In women with severe preeclampsia VEGF levels were 54.0 (19.9-192.4) ng/mmol creatinine, significantly (p<0.0001) higher than levels in pregnant controls (28.2 (6.7-63.0) ng/mmol creatinine) and non-pregnant controls (29.5 (10.1-59.1) ng/mmol creatinine). Proteinuria was not significantly correlated with urinary VEGF levels. In conclusion, high urinary VEGF concentrations in severe preeclampsia might reflect increased renal production of VEGF rather than elevated VEGF levels in the systemic circulation.     

Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia

During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.     

Changes in urinary pregnandiol and estriol excretions during second trimester abortion induced by trichosanthin: a protein extracted from Radix trichosanthei]

Urinary pregnandiol and estriol levels were estimated by gas-liquid chromatography during abortion in 14 second-trimester pregnant women induced by 5-12.5 mg Trichosanthin. The plant protein was injected intramuscularly in 12 women and intraamniotically in 2. In all the cases studied, urinary hormone excretion increased temporarily after the administration of the drug; then decreased gradually to an extremely low level before and after parturition. The relationship between the changes of urinary hormone levels and the effects of Trichosanthin upon placental function are discussed. (Authors' modified)     

Increase in urinary thromboxane excretion during pregnancy and labor

Urinary TXB2 excretion was measured during pregnancy and labor using high pressure liquid chromatography and radioimmunoassay. From the first trimester onwards TXB2 levels in urine of pregnant women (n = 60) were significantly (p less than 0.001) higher than in non-pregnant women (n = 12) and they increased, albeit not significantly, with advancing gestation. Labor was associated with a two-fold increase in urinary TXB2 excretion. Levels in established labor were significantly higher than at any other time in pregnancy (p less than 0.001), but the levels in incipient labor showed considerable overlap with these in late pregnancy. Thus urinary TXB2, while not necessarily originating from the pregnant uterus, appears to reflect the uterine activity of labor and may be the expression of a general stimulation of prostanoid production during parturition.     

Radioimmunoassay of 16 alpha-hydroxyestrone in human urine

A radioimmunoassay for the quantitation of the sum of free, glucuronidated and urine is described. The method is reliable and accurate. Using this method, urinary excretion of 16 alpha-hydroxyestrone was determined in normal men, premenopausal women, and postmenopausal women. The values were compared to the urinary excretion of estrone and estradiol. In two women, the urinary excretion of the three estrogens was measured in daily samples throughout a normal menstrual cycle. We conclude that 16 alpha-hydroxyestrone is a quantitatively important urinary estrogen. Inclusion of the measurement of 16 alpha-hydroxyestrone should yield a more accurate assessment of estrogen metabolism.     

Human urinary epidermal growth factor: effects of age, sex and pregnancy

Urinary concentrations of immunoreactive human epidermal growth factor (hEGF) were determined by specific homologous radioimmunoassay in 169 healthy men (aged 20-69 years), 275 healthy women (20-8 years). healthy women (20-68 years) and 413 pregnant women (20-39 years). Relative hEGF concentrations in urine (micrograms/g creatinine) decreased significantly in both sexes between 24 and 64 years of age. The relative concentrations of hEGF in urine were significantly higher in women than in men at ages 20-69 years. The mean values of relative urinary hEGF concentrations in pregnant women in their twenties and thirties (30.0 +/- 0.7 micrograms/g creatinine and 29.6 +/- 1.2 micrograms/g creatinine) were significantly higher than those in age-matched nonpregnant women (27.3 +/- 1.8 micrograms/g creatinine and 22.8 +/- 0.7 micrograms/g creatinine). Among the trimesters, it was highest in the 2nd trimester of women in the twenties and thirties (33.4 +/- 1.3 micrograms/g creatinine and 31.7 +/- 1.9 micrograms/g creatinine). The significance of the increased urinary excretion of hEGF (micrograms/g creatinine) in pregnancy is not known. Further studies are required to find a source of hEGF in urine and a possible relation between increased hEGF excretion and fetoplacental growth and development.     

24 h urinary creatinine excretion during pregnancy and its application in appropriate estimation of 24 h urinary iodine excretion

BackgroundUrinary creatinine can be used to adjust urinary iodine to evaluate iodine nutritional status during pregnancy. However, the reference intervals and impact factors of urinary creatinine are unknown.Methods24 h urine creatinine concentration (24 hUCr) and spot UCr at four different time periods of the day of pregnant women from Part 1 (n = 743) were measured. Linear regression analysis was performed to identify the impact factors of 24 h urinary creatinine excretion (24 hUCrE) and obtain the estimated 24 h urinary creatinine excretion (24 hUCrE_est). Then measured urinary iodine concentration (UIC) of 24 h and at fasting of pregnant women from Part 2 (n = 325), used spot urinary iodine to creatinine concentration ratio (UIC/UCr) and 24 hUCrE_est to calculate the estimated 24 h urinary iodine excretion (24 hUIE_est), finally checked the consistency and correlation of 24 hUIE_est and 24 h urinary iodine excretion (24 hUIE).ResultsIn Part 1, the median 24 hUCrE was 1.24(IQR0.98–1.76)g, and the reference interval was 0.61−2.93 g. The median 24 hUCr was 0.76 (IQR0.57−1.01)g/L, and the reference interval was 0.36−1.88 g/L. Multiple linear regression results showed that pregnancy weight was an influencing factor to 24 hUCrE after adjusting by gestational weeks, age, pre-pregnancy BMI, and percentage of body fat (F = 45.029, p＜0.001). In Part 2, there was no statistically significant difference between 24 hUIE_est and 24 hUIE (Z =−0.767, p = 0.443). Using 24hUIE as the gold standard, the relative average difference in 24hUIE_est was 4.2 %, the relative average differences for UIC and UIC/UCr were 32.4 % and 37.2 %. The reference interval of 24 hUIE and 24 hUIE_est were 88.43–585.90 μg and 50.97–700.39 μg, respectively.ConclusionsThe reference intervals of 24 hUCrE, spot UCr, 24 hUIE, and 24 hUIE_est during pregnancy were established. 24 hUCrE has important application value in iodine nutrition evaluation to gain more lead time for pregnant women with iodine nutrition-related diseases.     

Urine Iodine Levels in Preeclamptic and Normal Pregnant Women

The aim of this study was to investigate the urine iodine concentration in women with severe preeclampsia and in healthy women in Erzurum, Turkey. Urine specimens were obtained from 40 severe preeclampsia and 18 healthy pregnant women. Urinary iodine levels were determined by the Foss method based on the Sandell–Kolthoff reaction. The urinary iodine level for women with severe preeclampsia was 4.25 ± 2.7 μg/dL, lower than 20.89 ± 6.4 μg/dL of urinary iodine for healthy pregnant women (p < 0.001). Blood magnesium concentration was found to be 1.63 ± 0.05 mg/dL for women with severe preeclampsia, which is lower than that of healthy pregnant women (1.87 ± 0.05 mg/dL; p < 0.001). There was a positive correlation between urinary iodine level and blood magnesium level in pregnant women with preeclampsia (Pearson correlation coefficient = 0.43; p < 0.01). However, there was no correlation between urinary iodine level and blood magnesium level in healthy pregnant women. There was no difference in thyroid hormone levels (T4, TSH, FT4) between women with severe preeclampsia and healthy pregnant women. However, there was a difference in T3 thyroid hormone levels between women with severe preeclampsia (1.86 ± 0.4 μg/dL) and healthy pregnant women (1.45 ± 0.3 μg/dL; p < 0.001). There was also a difference in FT3 between women with severe preeclampsia (2.77 ± 0.4 pg/mL) and healthy pregnant women (2.41 ± 0.5 μg/dL; p < 0.01). Urinary iodine excretion is currently the most convenient laboratory marker of iodine deficiency. The method is useful for the rapid and low-cost assessment of iodine deficiency. Our results suggested that urinary iodine concentration might be a useful marker for prediagnosing preeclamptic women. In addition, iodine supplementation may also be considered for preeclamptic therapy.     

Formiminoglutamate excretion in rat urine after whole body irradiation, histidine administration, starvation and stress.

Formiminoglutamate (FIGLU) urinary excretion was studied in rats subjected to whole body 60Co irradiation with doses of 450, 650 and 850 R. During the first post-irradiation days, FIGLU excretion doubled after both lower doses. From day 3, 450 R led to a decrease, whereas 650 and 850 R were followed by a still enhanced FIGLU excretion. No correlation to the radiation dose was found. A daily intraperitoneal administration of histidine in a dose of 200 mg/kg led to a constant 5-fold increase of FIGLU output and to more distinct differences in post-irradiation FIGLU excretion. Two days starvation or ACTH administration, followed by doubled urinary total 17-hydroxycorticoids, did not interfere with FIGLU excretion.     

Effect of furosemide on urinary excretion of prostaglandin E in normal volunteers and pateints with essential hypertension

Urinary excretion of prostaglandin E was measured radioimmunologically in 19 healthy persons ( 15 men and 4 women ) and in 16 patients ( 10 men and 6 women ) with essential hypertension before and after the administration of furosemide. The excretion rates were increased from 26.3±3.0 to 64.5±11.3 ng/hr in the former and from 11.9±2.7 to 26.9±85 ng/hr in the latter. There was a significant difference between them, healthy subjects showing a greater increase than patients with essential hypertension.There was an obvious sexual difference in urinary excretion of prostaglandin. In men, greater increase in the excretion rates was found than in the women. Greater increases were also obtained in healthy men than in hypertensive men and in healthy women than in hypertensive women. The present results suggest that furosemide enhances urinary excretion of prostaglandin E by mechanisms which entails either an increase in prostaglandin synthesis or a decrease in renal metabolism.