C.J.A. van den Hamer

The influence of the method of preparation of the bone scanning agent 99mTc(Sn)EHDP on its tissue distribution in the rat

The tissue distribution in the rat of the bone scanning agent 99mTc(Sn)EHDP is investigated by three methods, viz. by dissecting the animals 3 and 24 h post injection, by scanning the animals with a rectilinear scanner and by whole body autoradiography, particular of micro-sections of the skeleton. The effect of varying the experimental conditions in the preparation of the bone scanning agent (pH and concentrations of Sn(II) and EHDP) is investigated. In some of the experiments additional amounts of Sn(II) and EHDP are added to the reaction mixture after the preparation of the bone scanning agent. In this way the influence of the Sn(II) and EHDP concentrations on the composition of the bone scanning agent, and their influence as such on tissue uptake can be separately investigated. The 99mTc-uptake in bone is compared with the distribution of the 99mTc over the two main products in the reaction mixture, viz. 99mTc(IV)-Sn-EHDP2 and 99mTc(IV)-Sn-EHDP. In addition, the stability in vitro of some of the preparations in urine and plasma and the in vivo binding of the 99mTc to plasma proteins are determined. A procedure for the preparation of the bone scanning agent is recommended.

Cultured skin fibroblasts: useful for diagnosis of Wilson's disease?

SummaryThe copper content of and radiocopper uptake in fibroblast cultures were studied to evaluate their usefulness for the diagnosis of Wilsons disease. We used methods closely related to those described in the literature, and applied these to cell lines of six patients with Wilsons disease and 12 controls. The results were:(1)The copper content of the cytosol of skin fibroblasts derived from patients with Wilsons disease was lower than that of controls when the cells were grown in a medium with a low copper concentration (0.7 µmol L−1); increased copper concentration (157 µmol L−1 in the medium failed to demonstrate any difference between normal fibroblasts and those derived from patients with Wilsons disease.(2)Radiocopper uptake studies did not differentiate between normal fibroblasts and fibroblasts from patients with Wilsons disease. We conclude that the cytosolic copper content of fibroblasts grown in a low copper medium is a potential diagnostic tool in Wilsons disease. At present not all controls can be distinguished from the Wilson cells; ways must be sought, therefore, of improving the technique.

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 mumols zinc (2.5 mumols/l). Possible errors in urine zinc determinations due to zinc contamination from catheters are calculated. Recommendations are made for minimizing these errors.

6 HOW TO DIAGNOSE ZINC-DEFICIENCY|[quest]|

Zinc-deficiency occurs in well-nourished children and is mostly of dietary origin. Vulnerability to infection, diarrhea, anorexia and growth retardation is its consequence. Easy reliable techniques to diagnose Zn-deficiency are not available. We have studied for this purpose:-].salivary-Zn (0.08±0.03), urinary-Zn (480±135 ppm/day) and plasma-Zn (0.86±0.15 ppm steady decreasing for 6 hr after 100 mg egg) in volunteers (in one person no plasma decrease) .-2.erythrocyte-Zn and in vitro uptake of 65-Zn in Zn-deficient rats (dietary-Zn v uptake r=0.99).-3.the behaviour of tracer Zn in mice (65-Zn, biological T½, excretion and distribution), and humans (69m-Zn figl). For pediatric use we have developed a stable-Zn loading test (68-Zn fig2). We expect the in vitro 65-Zn uptake by erythrocytes becomes a routine test to reliably diagnose Zn-deficiency.Zinc-deficiency occurs in well-nourished children and is mostly of dietary origin. Vulnerability to infection, diarrhea, anorexia and growth retardation is its consequence. Easy reliable techniques to diagnose Zn-deficiency are not available. We have studied for this purpose:-].salivary-Zn (0.08±0.03), urinary-Zn (480±135 ppm/day) and plasma-Zn (0.86±0.15 ppm steady decreasing for 6 hr after 100 mg egg) in volunteers (in one person no plasma decrease) .-2.erythrocyte-Zn and in vitro uptake of 65-Zn in Zn-deficient rats (dietary-Zn v uptake r=0.99).-3.the behaviour of tracer Zn in mice (65-Zn, biological T½, excretion and distribution), and humans (69m-Zn figl). For pediatric use we have developed a stable-Zn loading test (68-Zn fig2). We expect the in vitro 65-Zn uptake by erythrocytes becomes a routine test to reliably diagnose Zn-deficiency.

Normal hair zinc levels of children : Are they affected by drinking-water hardness?

From literature data, a negative correlation was derived between the normal average hair zinc levels of 5-yr-old children and the calcium levels in their drinking water (hair zinc level in mg/kg=−(0.158±0.003) calcium level in mg/L+134;r=0.993,n=6,p=0.0006). Exposure of hair samples of a 5-yr-old child to water with different levels of calcium and zinc did not provide evidence for an exogenous effect of calcium in drinking water on hair zinc levels. Thus, these results support Gibson’s hypothesis that calcium in hard drinking water interferes with Zn absorption.From literature data, a negative correlation was derived between the normal average hair zinc levels of 5-yr-old children and the calcium levels in their drinking water (hair zinc level in mg/kg=-(0.158±0.003) calcium level in mg/L+134;r=0.993,n=6,p=0.0006). Exposure of hair samples of a 5-yr-old child to water with different levels of calcium and zinc did not provide evidence for an exogenous effect of calcium in drinking water on hair zinc levels. Thus, these results support Gibsons hypothesis that calcium in hard drinking water interferes with Zn absorption.

Oral 65Zn Loading Test in Rats Fed Iri-Ob Diet with Various Zn Concentrations

The metal Zn is of biological importance as cofactor in enzymes, active in all major metabolic pathways. Deficiency of Zn is characterized by delay of cell multiplication and tissue growth. No specific biochemical indicator of deficiency is available. Homeostatic mechanisms in deficiency state have been proven by radiotracer whole body retention studies: the increase of biological halftime Tb is a reliable tool to diagnose (degrees of) Zn deficiency. Laboratory animals provide a suitable model to study the physiology of the homeostasis. Rats and mice react immediatelly with growth retardation when becoming Zn deficient (1). Available radiotracers for retention studies are 65Zn (Tf=235 day, ϒ-peak 1. 12 MeV) and 69Zn (Tf=12h, ϒ-peak 0.44 MeV).

Investigation of the zinc status of surgical patients—II. Influence of vascular reconstruction on the zinc status

Patients admitted for major vascular reconstruction operations received an i.v. dose of 65Zn. From the increased whole-body retention of 65Zn and the findings on other parameters it was concluded that the was concluded that the post-operative zinc metabolism of these patients differed from that of the control subjects. Unexpectedly, this difference persisted for several months. These patients can probably serve as controls in studies of patients who have undergone surgery of the intestinal tract. Increase of whole-body retention of 65Zn may be a sensitive indicator for subclinical zinc deficiency, but application in practice is hampered by the long duration of the period required for the measurement. From the present results it seems likely that measurement of the retention of 65Zn in the forearm as a function of time yields the same information but in a considerably shorter time.

Iodine-129 as a protein label for studies of plasma protein turnover and its measurement with neutron activation analysis

Abstract Iodine-129 ( t 1 2 = 1.57 × 10 7 y ) was used as a protein label for the measurement of the turnover rate of albumin in two human subjects. Plasma samples were assayed for 129I using destructive neutron activation analysis. The experiment entailed an estimated radiation dose of 0.2 μSv to the total body of the subjects. The turnover parameters showed reasonable agreement with literature values. When in a rabbit the catabolism of (129I + 131I)-labeled autologous albumin was followed, the results obtained with both labels agreed well.

35 THE EVALUATION OF TREATMENT WITH ORAL ZINC FOR WILSON'S DISEASE

Copper toxity in liver, brain, kidney due to a congenital failure of the copper biliary excretion mechanism in the liver is the nain problem in patients with M. Wilson. Oral zinc sulphate as sole treatment has been used succesfully for seven years as an alternative therapy for D-Penicillamin (D-P) which has sometimes serious side effects.A comparison of both forms of treatment was done in 2 sets of children with M.Wilson. Quantitative balance studies were performed using a standardized hospital diet and identical food portions frozen for analysis. All fecal and urinary excretions were sampled each day for a seven day period.Separately an oral 64-Cu test was done to measure copper uptake, and a single test dose of D-P given to determine copper excretion. Symptoms were absent and liver functions normal in all patients at time of the study.Conclusion: oral zinc treatment for M.Wilson in children is effective by blocking the intestinal uptake of copper.