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Biomedical subjects

C J Van den Hamer

Publications and source records attributed to C J Van den Hamer.

At least 19 recordsLinked to original sources

Effects of elevated zinc intake on the copper metabolism and the pancreas of the mouse.

The effects of moderately elevated zinc (Zn) intake on copper (Cu) metabolism and on the pancreas were studied. Zn (80 mg/L) as acetate was added to the drinking water of male Swiss mice for up to 12 weeks, which increased the total daily Zn intake to about 5 times the adequate level. Total Cu and Zn in tissues was measured by atomic absorption spectrometry. 64Cu was used to measure some effects of the Zn suppletion on the Cu metabolism. Furthermore, ceruloplasmin and amylase in plasma and superoxide dismutase in erythrocytes were measured. The pancreas was examined by light microscopy. The Zn supplementation decreased the 64Cu absorption and increased the retention of 64Cu, but did not lead to a Cu deficiency. Microscopic examination of the pancreas revealed focal hypertrophy of acinar cells, occasionally accompanied by vacuolation of cytoplasm and/or the presence of degenerated cells. The results, obtained in mice given a moderately increased Zn intake, should be interpreted as a warning against the chronic use in man of high doses of Zn for non-medical purposes.

Amylases↗

Zinc and copper of fetal organs during the second trimester of pregnancy.

In fetus with a mean gestational age of 18 weeks (range 15-25, n = 14), zinc and copper concentrations in liver, femur, rib, and skeletal muscle were measured. Zinc and copper concentrations are highest in liver. A trend of decreasing liver zinc concentrations during gestational age is suggested. Zinc concentrations are significantly correlated with copper concentrations in liver and in femur, suggesting steady growth in both organs. Femur zinc values rank ca. 30% of those in liver, femur copper, ca. 2%. Zinc or copper concentrations in rib are of the same levels as in skeletal muscle. Their concentration for zinc ranks ca. 20%, for copper, ca. 5% of the values in liver. All zinc and copper values are lower than reported in third trimester fetal organs. Calculated zinc/copper molar ratios are distinctive for the various organs: in liver, 6 +/- 1, in femur, 73 +/- 8, and in soft tissues, 26 +/- 3. Calculated ratios from published values obtained from the third trimester of pregnancy show that the ratios in liver and skeletal muscle maintain these levels. The zinc/copper molar ratio can serve as an internal reference in zinc and/or copper measurements.

Bone and Bones↗

Laboratory assessment of early dietary, subclinical zinc deficiency: a model study on weaning rats.

Male weaning rats were pair-fed a low-zinc diet or a control diet. After 10 d, the animals fed the low-zinc diet showed physiologic signs of deficiency; however, they showed no clinical symptoms. Their estimated whole body zinc was 25 mumol versus 39 mumol for the controls. The 65Zn absorption increased 2-fold and the tissue distribution altered: muscle and erythrocytes contained more, small intestine and liver less activity at 0.5 h postdose. In vitro, the erythrocyte 65Zn uptake rate increased also. The 65Zn uptake experiments required small quantities of erythrocytes. The difference observed between the deficient and control cells was significant and showed little overlap. The increase of the 65Zn uptake from a medium was not affected when the animals underwent endotoxin exposure 24 h before, as was reported to occur in whole blood 65Zn uptake. Therefore, we suggest the in vitro erythrocyte 65Zn uptake, performed in a standardized, near physiologic medium, to detect early, subclinical zinc deficiency.

Animals↗

A histidine supplement and regulation of the zinc status in Swiss random mice.

The effects of histidine on the zinc status are controversial. In mice, we studied the effects of a moderate histidine supplement on the regulation of the zinc status using subcutaneously administered 65Zn. In animals fed a zinc-adequate diet, histidine supplement did not cause changes in the zinc status (zinc concentrations, 65Zn tissue distribution, and tissue specific activities). Neither effects on the regulation of the zinc status (65Zn retention, excretion and biological half-life) could be demonstrated. However, the combination of a low zinc diet and moderate histidine supplementation caused changes in the regulation of the zinc status (lower 65Zn retention, associated with increased fecal excretion and a shorter biological half-life), aggravating the dietary deficiency (lower bone zinc, a shift in the 65Zn tissue distribution). Reviewing the literature, it seems that only a molar histidine/zinc ration of 2,000 or higher will cause zinc deficiency.

Animals↗

In vitro exchangeable erythrocytic zinc.

Exchangeable erythrocytic zinc is measured by 65Zn uptake in and release from erythrocytes under standardized and near, physiological conditions: 7.6 microM zinc and 580 microM albumin in the medium. The intracellular exchangeable erythrocytic zinc pool in healthy volunteers amounts to 5 mumol zinc/L packed cells. The half-time of the exchange is 7 h, its activation energy 84 kJ/mol. The effects of the variation in temperature and the concentrations of albumin, as well as the effects of some zinc carriers, cell transport inhibitors, and stress hormones on the 65Zn uptake are measured.

Adult↗

Discrimination between low dietary zinc and endotoxin exposure: a model study on weaning rats.

To establish a parameter for zinc status that is independent of the occurrence of infection, we studied the effects of low dietary zinc and endotoxin in weaning rats 21 d after 65Zn intubation. We monitored aspects of zinc status (tissue zinc content, 65Zn distribution, and specific 65Zn activity in tissue) and 65Zn metabolism (absorption, excretion, and biologic half-life), as well as weight gain, feed conversion, and dietary zinc use. The low zinc diet induced classical deficiency with losses of bone zinc, resulting in lower content (7.4 versus 19.6 mumol) and higher spec act (17 versus 8 kBq/mumol). Other tissue-specific and plasma-specific activities were also higher (overall, 20 versus 8 kBq/mumol; plasma, 8 versus 4 kBq/mumol). Endotoxin caused lower total-plasma zinc (0.04 versus 0.05 mumol) but did not affect spec act (4 kBq/mumol); combined endotoxin and low-zinc diet caused low total-plasma zinc (0.01 mumol) and high spec act, as did the low-zinc diet alone (12 kBq/mumol). We conclude that plasma-spec act (or stable isotope enrichment) can serve as an index for nutritional zinc status during recurrent infection.

Administration, Oral↗

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

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

Adult↗

Histidine supplement and Zn status in Swiss random mice.

The influence of either histidine supplement or nutritional Zn deficiency on growth and the organ and tissue Zn content of mice during a 21-d period was compared with a control group. When the histidine intake was increased from 5 to 9 mumol/g body wt/d we noted increased body weight and higher Zn concentrations in liver, pancreas, spleen, and muscle. As a result, the estimated whole body Zn mass increased. This was explained by enhanced utilization of dietary Zn. These results differed from those seen in Zn deficient animals (fed 5 nmol Zn/g body wt/d instead of 29). Dietary Zn deficiency was characterized by anorexia and growth retardation, lower Zn concentrations in pancreas, muscle, bone, tail, and plasma, plus higher Zn concentrations in spleen and fur. As a result, the estimated total body Zn mass was 20% lower than in the control animals, despite a two-to threefold increase in utilization of dietary Zn. These results are discussed in view of the available literature. It is concluded that in humans and in animals both the absorption and the excretion of Zn may be increased by histidine. Below a certain dose the former will prevail, viz., a situation of increased utilization exists, preventing the development of Zn deficiency.

Animals↗

Dietary zinc deficiency has no effect on auditory brainstem responses in the rat.

Zinc has been shown to effect--in vitro--a number of processes associated with neurotransmission. We have tested whether the rate of impulse conduction--in vivo--as measured from the latencies of auditory brainstem responses (ABR), is influenced by dietary zinc deficiency in the rat. Dietary zinc deficiency for up to 26 wk had no effect on the wave I-IV interval compared to zinc-adequate fed animals. The results are discussed in relation to the observed constancy of brain overall and extracellular fluid zinc concentrations under conditions of dietary zinc deficiency.

Animals↗

Effect of excess dietary histidine on rate of turnover of 65Zn in brain of rat.

The effect of the chronic administration of histidine on the brain zinc level was examined in growing, male Wistar rats. Using a purified diet, the minimum zinc requirement for normal growth and normal plasma and tissue zinc levels was found to be around 10 ppm. Given this zinc content, the diet was supplemented with 5% and 8% histidine, respectively, or with 10% glycine (as control). Brain zinc was analyzed by measuring the rate of turnover of 65Zn from 2-4 weeks after a single injection of the tracer. Feeding the diet supplemented with 5% histidine caused a small decrease in the plasma zinc concentration and a slight increase in the rate of turnover of 65Zn in the cerebrum and the cerebellum as compared to the control group. The animals fed the diet supplemented with 8% histidine became severely zinc deficient (as evidenced by a 50% reduction in the plasma zinc content), however, the rate of turnover of 65Zn in all brain regions examined was significantly decreased as compared to the control group. The results indicate that histidine has no specific complexing action on the brain zinc.

Animals↗

Zinc uptake into synaptosomes.

Zinc uptake was studied in synaptosomes, isolated by the Ficoll flotation technique, using the radiotracer 65Zn. True uptake of zinc could be discriminated from binding to the outside of the synaptosomes by the absence of accumulation at 0 degree C and the dependency of the rate of uptake on the medium osmolarity. The zinc uptake, studied in the presence of various zinc-complexing agents, showed saturation kinetics when analyzed in terms of [Zn]free, yielding Km = 0.25 microM. The zinc uptake was independent of both ATP and the Na+ gradient. No efflux of zinc could be demonstrated from preloaded synaptosomes due to the formation of insoluble zinc complexes inside the synaptosomes. The results are discussed in terms of the modulation of diverse neurochemical processes by zinc.

Adenosine Triphosphate↗

The effect of dietary zinc deficiency on the mossy fiber zinc content of the rat hippocampus. A microbeam PIXE study. Particle Induced X-Ray Emission.

The effect of dietary zinc deficiency on the mossy fiber zinc content of the rat hippocampus was investigated using PIXE (Particle Induced X-Ray Emission) spectroscopy. Using the proton microbeam (60 X 60 microns), 2 mm line-scans were made on hippocampal sections and the data were expressed as absolute zinc concentrations. Values of 55 and 136 ppm (dry weight) were found for the mean background zinc level and the maximum mossy fiber zinc level, respectively, in animals fed a control diet containing 50 ppm zinc. Treatment of these animals with dithizone caused about 50% reduction in the maximum mossy fiber zinc level. Feeding a zinc-deficient diet for 28 days did not cause a decrease in the mossy fiber zinc level, however, feeding the zinc-deficient diet for 90 days reduced the maximum mossy fiber zinc level by about 30%. The results are discussed in relation to the behavioral abnormalities that have been observed in zinc-deficient animals.

Animals↗

Management of Wilson's disease with zinc sulphate. Experience in a series of 27 patients.

Evaluation of the literature concerning the various approaches for the treatment of Wilson's disease led to the conclusion that zinc sulphate might be a good choice because it is effective and relatively safe. Twenty seven patients were managed with zinc sulphate for a total period of 142 patients-years. The drug was administered in doses varying from 300 to 1200 mg/day. Of the 9 patients who were treated with zinc from the start, 8 improved and one died from severe cirrhosis. All 8 patients who were placed on zinc after intolerance to penicillamine did well on zinc therapy. Ten patients were changed to zinc after they had first been treated with penicillamine without developing signs of intolerance. Of this group 8 patients were kept on long-term zinc therapy, 2 were changed back to penicillamine because of personal preference. Signs of intolerance to zinc were not observed. All patients kept a diet containing about 1.2 mg of copper a day. Our experience supports the idea that zinc sulphate is a good choice for the treatment of Wilson's disease: the drug is effective, safe and cheap.

Copper↗

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.

Aged↗

Influence of Ca and Mg on the uptake and deposition of Pb and Cd in mice.

The influence of high but not extreme concentrations of Ca and Mg (25 mumol/ml) on the apparent absorption and retention of 203Pb and 115mCd from water was investigated in mice. Ca reduced the absorption of Pb from an intubated solution by 62% and the absorption of Cd by 22%, but these effects were not significant. Mg showed no effect on Pb and Cd absorption. The retention of ip-injected Pb and Cd was not influenced by addition of Ca or Mg to the drinking water. Feeding of a Ca-deprived diet for 2 weeks prior to dosage stimulated the absorption of Pb from water by more than 100% (p less than 0.01) and the absorption of Cd from water by 17% (p less than 0.05). Feeding of a Ca-supplemented diet did not influence the absorption of Pb or Cd, but fecal Cd excretion seemed to be reduced. Feeding of Mg-deprived or Mg-supplemented diets did not show any effect on Pb and Cd metabolism. These results give supporting evidence that in soft water regions the uptake of Pb from the drinking water could be increased because of the absence of Ca in the drinking water, particularly when dietary Ca intake is low. This relationship between drinking water hardness and absorption of Pb could be important in view of general public health.

Animals↗

Effective treatment of Wilson's disease with oral zinc sulphate: two case reports.

Most patients with Wilson's disease are treated with the potentially toxic cupriuretic agent penicillamine. The toxicity of zinc taken by mouth is low, and long term administration induces a negative copper balance. Two patients with severe neurological symptoms were given zinc sulphate by mouth three times daily in doses of 200 mg, later increased to 300 mg. One patient, a 21 year old man, started to receive zinc sulphate after his condition had deteriorated during treatment with cupriuretic drugs. The other, a 27 year old woman, was treated from the start with zinc sulphate. The conditions of both patients improved appreciably, and they were still receiving treatment with zinc sulphate roughly two years later. Effective depletion of body copper stores was shown by an intravenous radiocopper loading test and liver biopsy. No side effects were found. Wilson's disease may effectively be treated with zinc sulphate alone.

Administration, Oral↗

Investigation of the zinc status of surgical patients.

Zn kinetics were studied in two surgical patients and compared with the findings in three controls. One patient had malabsorption following resection of part of the small intestine, the other was suffering from malabsorption due to radiation enteropathy incurred more than 10 years earlier. Whole-body retention of i.v. administered 65Zn, measured with a simple linear scanner, showed a sharp initial drop in the first patient, followed by an increased retention. This was explained by large initial intestinal losses of Zn leading to a state of Zn deficiency. In the second patient, who had developed Zn deficiency over a period of years, the whole-body retention was increased from the beginning. Compared with other parameters, whole-body retention seems to be a good indicator for the Zn status of patients, although of limited clinical use because the measurements take too much time.

Adult↗