Urinary Zinc Concentrations Research Articles

Are Disturbances of Zinc Metabolism in Human Immunodeficiency Virus Type I (HIV-I) Infection Caused By Immune Activation?

Summary The activation of the immune system is associated with profound alteration of zinc metabolism. In human immunodeficiency type 1 (HIV-l) infection serum zinc is frequently decreased. To investigate a potential role of immune system activation on urinary zinc wasting, we compared urinary zinc and l1eopterin levels in 52 patients with HIV-J infection. In addition, serum zinc was studied in 25 of the patients. We confinned earlier reports of decreased serum zinc levels in the patients. As expected, urinary neopterin was significantly increased in HIV-l infection, the highest values being reached in AIDS patients. Urinary zinc concentrations were not statistically different between patients and controls. However, a positive correlation existed between urinary zinc and neopterin levels and between neopterin and zinc clearance coefficient in patients with more advanced stages of HIV infection. No correlation between serum zinc and urinary neopterin or urinary zinc was found. The data indicate that, in addition to malabsorption, chronic immune activation may contribute to the development of zinc deficiency by urinary zinc wasting.

Meal-induced changes in plasma, erythrocyte, and urinary zinc concentrations in adult women

We attempted to determine whether there is a limit to the transient, meal-induced decline in plasma zinc and whether there is a concomitant increase in erythrocyte and erythrocyte membrane concentrations. Premenopausal women participated in a 17-h fasting trial, a one-meal trial with breakfast at 0700, and a three-meal trial with meals at 0700, 0900, and 1100. During fasting, plasma zinc increased 9%; it decreased 11% and 19% in the one- and three-meal trials, respectively (P < 0.001). A limit to the decline in plasma zinc was reached after the second meal in the three-meal trial. Erythrocyte, erythrocyte membrane zinc, and serum calcium and phosphorus concentrations did not change significantly during the three trials. Serum glucose concentrations were weakly related to plasma zinc concentrations, suggesting that the postprandial decline in plasma zinc is associated with the metabolic changes caused by food intake.

On the excretion of zinc by the shore crabCarcinus maenas(L.)

Abstract The shore crab Carcinus maenas (L.) does not excrete zinc taken up and accumulated when exposed to 100 µg Zn l−1, but does excrete a proportion (c. 70%) of the zinc taken up from 3162 µg Zn l−1 over 21 days. Ofthe zinc excreted at this exposure, only 4% is excreted in the urine. There was a linear relationship between zinc concentrations in urine and blood. Food was found to be an important Zn source to the crab, and excretion ofZn accumulated from food again depended on dose. None of a c. 25 µg Zn dose in food was excreted in 12 days; of 210 µg absorbed from a 250 µg Zn dose in a meal 46% was retained after 12 days, and 113 µg was excreted (22% in the faeces, 1% in the urine and 77% probably via the gills). C. maenas lost c. 20% of the body zinc content with the moult, even after withdrawal into the soft tissues of some of the zinc there accumulated (both from food and water).

Indices of iron and copper status during experimentally induced, marginal zinc deficiency in humans.

This study examined the effect of diet-induced, marginal zinc deficiency for 7 wks in 15 men (aged 25.3 +/- 3.3 yrs; mean +/- SD) on selected indices of iron and copper status. The regimen involved low-zinc diets based on egg albumin and soy protein with added phytate and calcium such that mean [phytate]/[Zn] and [phytate] X [Ca]/[Zn] molar ratios were 209 and 4116, respectively, for 1 wk, followed by 70 and 2000, respectively, for 6 wks. Subjects were then repleted with 30 mg Zn/d for 2 wks. Plasma copper, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity in plasma and red blood cells (RBC), hemoglobin, hematocrit, and serum ferritin were determined weekly on fasting blood samples. Significant reductions (p less than 0.05) after 7 wks in RBC Cu,Zn-superoxide dismutase (49.5 +/- 7.2 vs 33.6 +/- 6.3 U/mg Hb) and serum ferritin (69.2 +/- 38.7 vs 53.8 +/- 33.7 micrograms/L) occurred; no comparable decline was noted for plasma Cu, hemoglobin, or hematocrit. Significant (p less than 0.05) but less consistent changes were also observed in plasma superoxide dismutase activity. None of the changes were associated with the decreases in plasma, urinary and hair zinc concentrations, and alkaline phosphatase activity in RBC membranes. Results indicate that the biochemical iron and copper status of the subjects was marginally impaired, probably from the dietary regimen that induced marginal zinc deficiency.

Zinc levels after intravenous administration of zinc sulphate in insulin-dependent diabetes mellitus patients

Diabetic patients commonly have increased urinary excretion of zinc, although blood concentrations may be normal, lowered, or raised. We analyzed zinc levels in plasma and urine after an intravenous overload of zinc sulphate (8 mg) in 22 patients with insulin-dependent diabetes mellitus (IDDM) and 22 healthy individuals. No significant differences were found in basal levels of serum zinc in either group (111 +/- 29 micrograms/dl in IDDM vs 119 +/- 19 micrograms/dl in controls), although urinary excretion of zinc was significantly raised in diabetics (1396 +/- 622 micrograms/24 h) versus controls (611 +/- 235 micrograms/24 h). After zinc overload, both serum and urinary levels of this element varied between the two groups. Serum zinc in IDDM patients initially increased more markedly, and subsequently showed a more significant decline, than in controls. Urinary zinc levels in IDDM patients, in contrast to control values, showed no increase after overload. These alterations in serum and urinary zinc concentrations suggest that our diabetic patients may be zinc-deficient.

Urinary zinc excretion in a patient with burns: a caveat when using bladder catheters in urine zinc studies

The results of a longitudinal study on plasma and urine zinc concentrations in a patient with 68 per cent burns are described. Special attention was paid to possible zinc contamination due to the use of bladder catheters for urine sampling. The course of the plasma and urine zinc concentrations during the first 50 days in hospital was comparable to those reported in the literature. It was shown that surgery was associated with a pronounced rise in urine zinc level, while catheter replacement caused no significant increase in urinary zinc content in this particular patient. However, measurements of zinc content of and zinc release from three types of bladder catheters showed that the two types of latex-based catheters contained about 0.25 per cent zinc, versus 0.01 per cent in the siliconelastomer equivalent. During an 8 h perfusion latex catheters released about 1.2 μmol zinc (2.5 μmol/l). Possible errors in urine zinc determinations due to zinc contamination from catheters are calculated. Recommendations are made for minimizing these errors.

Zinc status in human immunodeficiency virus infection

Plasma zinc and copper concentrations, erythrocyte zinc concentration, copper-zinc superoxide dismutase activity and urinary zinc concentrations were determined for control subjects and individuals with AIDS, ARC, or asymptomatic HIV infection. Significant differences among the population groups were not noted for the above parameters with the exception of plasma copper which was higher in the AIDS group than in other patient groups. These results do not support the idea that zinc deficiency is a common contributory factor of HIV infectivity or clinical expression, nor that HIV infection induces a zinc deficiency.

Ratio of Post‐prostatic Massage Urinary Zinc Concentration to Initial Urinary Zinc Concentration An Improved Method of Assessing Prostatic Function

Various methods have been used clinically to assess prostatic function. We evaluated a number of ways of using zinc in post-prostatic massage urine (VB3) and found that the ratio of VB3 zinc concentration to initial urinary zinc concentration was a good indicator of prostatic secretory activity. This ratio can differentiate hormonally treated patients with carcinoma of the prostate from those untreated and from those with benign prostatic hypertrophy. The specificity is increased for individuals by repeat samples. Comparison of samples before and after resection showed no loss of function and no difference was found between groups treated with orchiectomy or LHRH agonist (Zoladex). The VB3/VB1 zinc concentration could be used in a prospective study of hormonal treatments directed against the prostate, where it could give objective evidence of a fall in secretory function of the gland.

Urinary zinc excretion in Crohn's disease.

In order to study the reliability of urinary zinc levels as an index of zinc metabolism and status in Crohn's disease, we evaluated plasma and urinary zinc concentrations, urinary 3-methylhistidine excretion, and Crohn's disease activity index (CDAI) in 42 patients affected by Crohn's disease. Plasma zinc correlated directly with albuminemia (P = 0.01) and inversely with CDAI (P = 0.001). Urinary zinc excretion correlated with urinary 3-methylhistidine (P = 0.001) and plasma zinc levels (P = 0.01), and inversely with CDAI (P = 0.05). However, from multiple regression analysis, it was found that zincemia is influenced by CDAI and not by albumin, whereas zincuria is related to urinary 3-methylhistidine and plasma zinc, and not to CDAI. Our conclusion is that, in Crohn's disease, zincuria can be an index of zinc status when used together with measurements of lean body mass and turnover and factors influencing plasma ultrafiltrable zinc fraction.

Urinary zinc and metallothionein in children with spina bifida

Defective embryonic cellular zinc utilization may contribute to abnormal neural tube formation and such a defect may be detectable in children with spina bifida (SB). To investigate this possibility, we examined urinary excretion of zinc and metallothionein (Mt), a cytoplasmic metal-binding protein, in 10 girls and 6 boys (ages 6 months to 19 years) with SB and 16 age-matched control subjects. Mean urinary zinc and Mt concentrations in the SB group were 65% and 72% greater than controls, respectively (p < 0.05). There was was no evidence of renal dysfunction as judged by urinary creatinine and total protein excretion in the SB children. Increased excretion of zinc and Mt in some children with SB may reflect one or more underlying defects of zinc utilization.

Interaction between Ethanol and Low Dietary Zinc during Gestation and Lactation in the Rat

Pregnant rats were fed individual liquid diets throughout gestation and lactation. The diets contained either 2 or 10 µg zinc/ml diet with or without 30% of the kilocalories supplied from ethanol. The low zinc diet produced a moderate zinc deficiency in dams evidenced by decreases in tissue zinc content, serum alkaline phosphatase activity and urinary zinc concentration. Despite the presence of high zinc content in the diet, ethanol antagonized the maternal zinc status to a level typical of that produced by the low zinc diet. The lowest zinc status, however, was found when low dietary zinc and ethanol were combined. The maternal interaction between ethanol and zinc also depressed offspring serum zinc and alkaline phosphatase activity in a similar manner. Ethanol, however, did not affect tissue content of calcium, magnesium or phosphorus, which indicates that ethanol is a specific antagonist of zinc utilization during gestation and lactation.

Acute effects on chromium, copper, zinc, and selected clinical variables in urine and serum of male runners

Nine male runners (23-46 yr) ran 6 mi near their maximal pace. Blood and urine samples were obtained prior to, immediately after, and 2 h following the run; 24-h urine collections were also taken on the run and nonrun days. Serum chromium increased significantly (P < 0.05) from 0.12 ± 0.02 (mean ± SE) to 0.17 ± 0.03 ng/mL immediately following running and remained elevated, 0.19 ± 0.03 ng/mL, after 2 h. Urinary chromium concentration was elevated several-fold 2 h following running and daily urinary chromium losses were about twofold higher on the day of the run compared to a rest day. Serum zinc was not significantly different from prerun values immediately following running, 81 ± 4 and 85 ± 4 pμg/dL, respectively, but then decreased significantly to 75 ± 4 2 h after exercise. Urinary zinc concentration was elevated more than twofold 2 h after running and total urinary losses on the day of the run were more than 1.5-fold higher than those on the nonrun day. Serum copper was not altered by exercise. Serum high density lipoprotein (HDL) cholesterol, but not total cholesterol increased significantly following running. HDL cholesterol values were similar to prerun values within 2 h of running. Serum triglycerides, phosphate, creatinine, bilirubin, uric acid, and alkaline phosphatase were also elevated immediately following running, whereas albumin, total protein, and blood urea nitrogen remained constant. These data demonstrate that accompanying the transitory changes in selected clinical indices caused by strenuous running there are alterations in chromium and zinc concentrations in serum and urine and increased specific urinary losses of these essential nutrients.

Copper and zinc levels in serum and urine of cadmium-exposed people with special reference to renal tubular damage

Urinary copper and zinc concentrations and their serum levels were determined in women environmentally exposed to cadmium, including “itai-itai” disease patients and suspected patients, for evaluating the effect of cadmium exposure on metabolism of such essential metals as copper and zinc in human beings. Copper concentrations in the urine of cadmium-exposed women, especially “itai-itai” patients and suspected patients, were much higher than those of nonexposed women. Zinc concentrations in the urine of cadmium-exposed women, however, were not different from those of nonexposed women. Zinc levels in the serum of the “itai-itai” patients were somewhat lower than those of the nonexposed women. On the other hand, serum copper was almost equal in the cadmium-exposed and the nonexposed women. The correlation coefficient between β 2-microglobulin amounts and copper concentrations in the urine of all women examined was as high as 0.95. It is concluded that exposure to cadmium will cause an increase in the excretion of copper in urine, which is attributable to renal tubular damage due to the cadmium exposure, and that urinary zinc excretion is not increased by cadmium exposure, even in the patients who suffer from severe renal tubular damage.

Ethanol-Provoked Disturbances in the Binding of Zinc to Rat Jejunal Mucosal Proteins

The present investigation was undertaken to determine whether administration of ethanol by intragastric intubation to rats modifies the binding of radioactive zinc to its binding proteins in the jejunal mucosa. These studies were prompted by the frequent observation of abnormalities in serum and urine zinc concentrations in alcoholic patients and the necessity to determine whether alcohol diminishes intestinal protein binding of zinc, the first step in zinc absorption. Adult female rats received intragastric ethanol by intubation, either daily for 10 days, or only 1 hour prior to death. After death by decapitation, the small intestine was removed, and mucosal cell extracts prepared by homogenization and centrifugation. These extracts were incubated with 65ZnCl2, and gel filtration chromatography was performed with Sephadex G-100. A major difference in the chromatographic profiles between control and alcohol-treated animals was observed: binding of zinc to high molecular weight proteins was reduced and that to low molecular weight proteins was increased. These differences occurred both 10 days and 1 hour after ethanol. The finding of diminished binding of zinc to high molecular weight jejunal proteins may represent the first step leading to diminished intestinal absorption of zinc in alcoholism.ethanol zinc jejunum absorption

Urinary zinc in relation to other cations and flow during volume expansion and intravenous chlorothiazide.

Urinary excretion of zinc, sodium, potassium, and calcium was studied in anesthetized dogs under conditions of volume expansion by saline infusion and volume expansion plus chlorothiazide administration. Zinc excretion was positively correlated to the fractional water excretion, as well as to th excretion of the other cations, during volume expansion. Chlorothiazide administration during volume expansion increased the zinc, sodium, and potassium excretion without changing that of calcium. The enhanced zinc excretion during chlorothiazide diuresis was equal to that expected on the basis of the increase in fractional water excretion alone. The urinary concentration of zinc appeared inversely related to the urine flow rate, reaching a minimum below that of the plasma ultrafilterable zinc concentration. The ratio of the clearance of zinc to that of sodium was 0.28, indicating a greater degree of net reabsorption for zinc than for calcium. These findings suggest that zinc and sodium reabsorption may be inhibited to a similar degree at chlorothiazide-sensitive sites in the tubule. Furthermore, the zinc reabsorptive mechanism seems capable of lowering urinary zinc concentration below that of ultrafiltrate and appears related in some way to sodium reabsorption.

Zinc metabolism in thyroid disease.

This study was designed to evaluate the zinc metabolism in adults of both sexes with thyroid disease. Plasma and erythrocyte zinc concentration and urinary zinc excretion were investigated. The mean concentration of plasma zinc in hypothyroid patients and in euthyroid patients, previously either hyperthyroid or hypothyroid, was lower than that of control subjects, whereas no statistically significant differences were observed in plasma zinc values between hyperthyroid patients and control subjects. The average erythrocyte zinc level in patients with thyroid disease was significantly lower than that in control subjects. Erythrocyte zinc concentration was significantly decreased in hyperthyroidism compared with hypothyroidism, or patients previously either hyperthyroid or hypothyroid but now euthyroid. Increased urinary zinc excretion in hyperthyroidism was noticed compared to euthyroid and hypothyroid patients and to control subjects. Increased urinary zinc concentrations may result from increased tissue catabolism such as muscle. The results of this study suggest that abnormal zinc metabolism occurs commonly in patients with thyroid disease.

Failure of oral l-histidine to influence appetite or affect zinc metabolism in man: a double-blind study

l-Histidine, 4 g/day in gelatin capsules, was administered orally to eight normal volunteers for 2 weeks in a double-blind, balanced, crossover study with 2 weeks of placebo treatment. Body weight, serum and urinary zinc and histidine concentrations, as well as subjective ratings of appetite, taste and smell perception, and food intake were monitored. l-Histidine therapy had no significant effect on appetite, taste and smell perception, food intake, or body weight. Similarly, no effects were observed on total serum zinc, albumin-bound zinc or α2-macroglobulin-bound zinc concentrations, or on urinary histidine excretion. Serum histidine concentrations increased with therapy. Urinary zinc excretion was increased significantly after 1 week, but not after 2 weeks of l-histidine therapy. It can be concluded that oral l-histidine, at the dose used, has no value as an anorectic agent.

Plasma Whole Blood and Urine Zinc in the Assessment of Zinc Deficiency in the Rat

Serial measurements of plasma, whole blood, and urine zinc have been made in young adult rats fed zinc deficient and zinc supplemented diets for a total period of 65 days. After commencing a zinc deficient diet plasma zinc fell within 48 hours to 25% of control values and remained at this level throughout the period of study. A substantial diurnal variation was observed in plasma zinc, and the level was significantly lower in the fasting state. Whole blood zinc was unaffected by fasting, showed no diurnal variation, and remained at control values even after 65 days of zinc deficient diet. Urine zinc fell to very low values, 10 days after commencing a zinc deficient diet, but after 30 days rose to control values. Under controlled conditions plasma zinc can be used as an indication of zinc deficiency. Whole blood zinc is of no value in the detection of zinc deficiency. Urine zinc concentration varies with time following a zinc deficient diet.

Altered copper and zinc metabolism in primary hyperparathyroidism.

Mean 24-hour urinary excretion of copper and zinc was greater than normal in 17 patients with untreated primary hyperparathyroidism. Mean total serum copper concentration in these patients was slightly greater than the normal mean, whereas mean total zinc concentration was normal. After surgical treatment of hyperparathyroidism there was a transient further increase in urinary copper and zinc concentrations in the 13 patients so studied, with no consistent change in serum copper or zinc concentrations. Five patients were studied for several days after this postoperative peak had passed. Urinary copper and zinc excretion decreased in three in relation to surgical correction of their hyperparthyroidism and remained elevated in one with persistent hypercalcemia. In the fifth patient urinary zinc excretion increased to slightly above the normal range despite successful surgery. These results suggest that changes in urinary excretion of copper and zinc may be useful indicators in the diagnosis and treatment of patients with primary hyperparathyroidism.

Dissociation of zinc excretion from other cations in man.

Abstract Zinc excretion was compared with sodium, potassium, calcium, and magnesium during clearance studies in 38 normal men. Base-line zinc excretion (per unit inulin clearance) averaged 44.2 ± 4.1 nEq. per 100 ml., and correlated modestly (r = 0.39) with plasma zinc concentrations. During isotonic saline loading, zinc excretion increased 28 per cent (P decreased 15 per cent while sodium, calcium, and magnesium excretion increased an additional 102, 61, and 33 per cent, respectively. After intravenous furosemide or ethacrynic acid, zinc excretion increased, but rapidly reverted to control values. In contrast, large increases in sodium, calcium, and magnesium excretion were maintained for 2 hours. Urine zinc concentrations decreased, while concentrations of sodium, calcium, and magnesium increased after diuretics. Although these studies do not elucidate the intrarenal mechanisms controlling zinc excretion, they do suggest that the renal handling of zinc differs markedly from other divalent cations.