Biomedical subjects

J P Van Wouwe

Publications and source records attributed to J P Van Wouwe.

17 recordsLinked to original sources

PubMed1995

Carnitine deficiency during valproic acid treatment.

Prolonged valproic acid treatment results in secondary carnitine deficiency. In thirteen children paired samples of plasma were drawn at the onset of, and after 9 months of continuous valproic acid treatment. At onset free plasma carnitine values were age dependent; they increased during childhood (r = 0.59, p = 0.016). After 9 months: 1 - mean plasma free carnitine decreased by 40%, from 32.7 mumol/l to 20.9 (p 0.0008 and 3% overlap; 2 - plasma total carnitine decreased by 20%, from 34.9 mumol/l to 27.1 (p 0.016 and no overlap); and 3 - the esterified/free carnitine ratio increased by 40%, from 0.28 to 0.39 (p 0.011 and no overlap). In two out of thirteen patients clinical symptoms were observed, fatigue, besides the biochemical evidence of carnitine deficiency. In four others only biochemical deficiency was found. If the child complains of fatigue during prolonged valproic acid treatment, it is advised to supplement carnitine. A dose of 15 mg/kg body weight is effective to reverse the clinical symptoms of carnitine deficiency within a week. The dose to prevent deficiency is not yet established.

Adolescent↗

PubMed1994

The role of the pancreas in the regulation of zinc status.

A low Zn diet resulted in subacute Zn deficiency in young rats. Thirty minutes after the intubation of a trace 65-Zn we determined the total tissue Zn activity in plasma, erythrocytes, liver, pancreas, bone, muscle, and proximal jejunum. Assuming the body behaved like a closed multicompartmental system in steady state, we estimated the initial Zn exchange between plasma, and the erythrocytes or these tissues. In comparison with control animals the exchanges between plasma and erythrocytes or pancreas increased threefold during subacute Zn deficiency. In the pancreas the ratio also reversed from < 1.0 to > 1.0. This confirmed earlier observations that the specific activity (kBq 65-Zn/mol Zn) increased mostly in the pancreas. By increased net Zn uptake during subacute deficiency, the pancreas Zn content remained constant in chronic Zn deficiency. We discussed the regulation of the Zn status by the pancreas. We hypothesize that the exocrine pancreas modulates Zn absorption by an exocrine ligand that enhances absorption in the jejunum during subacute deficiency: Unsaturated with Zn it binds dietary intraluminal Zn and increases the Zn absorption. The literature provides evidence in confirmation. This hypothesis explains also conflicting data on the inherited Zn malabsorption syndrome Acrodermatitis Enteropathica.

Animals↗

PubMed1994

Comparison between total and ultrafiltrable serum zinc as test to diagnose zinc deficiency in infants and children.

Total Serum Zinc (TSZn) and albumin were determined, and low molecular weight serum Zn measured by radiochemical UltraFiltration (UFSZn) in healthy Dutch infants and children, and in samples obtained from those with diseases that are expected to alter TSZn. Our control TSZn values, 10.2 +/- 3.5 mumol/L, were low compared to those reported in the literature. Variation in serum albumin could not explain this: No correlation of TSZn with serum albumin was found (p > 0.5). Likely explanations are the nonfasting state and the stress owing to hospital surroundings at the time of sampling. A range of other influences not registered may be active and are discussed. No significant age-dependence was found (p < 0.8). Boys over 9 yr of age showed higher TSZn compared with girls of the same age (p < 0.08). In a separate experiment a 17% decrease in TSZn was demonstrated by food intake (eggs). These results support the opinion that TSZn is of little value to measure Zn status. There was no discrimination in TSZn between healthy subjects and patients. Our UFSZn values, 0.28 +/- 0.13 mumol/L in the controls as well as in the patients, were correlated with TSZn and therefore not a suitable alternative for the measurement of TSZn as parameter to determine the Zn status. The UFSZn was not correlated with serum albumin (p < 0.7). UFSZn values were higher in infants (p < 0.01), no sex dependence was found. We conclude that TSZn as well as UFSZn are of limited clinical relevance.

Adolescent↗

PubMed1993

Changes of CSF-Cu and -Zn in children with acute lymphoblastic leukemia.

In 20 Dutch children with acute lymphoblastic leukemia (ALL), Cu and Zn levels in cerebrospinal fluid (CSF) were studied during standard treatment (Protocol ALL-BFM-86/SNWLK-ALL-VII). CSF-Cu in 10 controls was 0.04 +/- 0.02 mumol/L, lower compared to values in adults. At the moment of diagnosis, CSF-Cu values were higher, 0.06 +/- 0.03 mumol/L, and during maintenance therapy lower, 0.01 +/- 0.01 mumol/L. Children with central nervous system (CNS) involvement ALL as judged by CAT Scan and EEG--in addition to cytology--showed lower CSF-Cu values compared to children without. CSF-Zn values were also measured. CSF-Zn was 0.05 mumol/L and did not vary. Cu/Zn molar ratios were increased at the onset of treatment, and decreased during maintenance therapy. The changes in CSF-Cu may follow the natural course of the disease or may relate to the success of treatment, reflecting a decrease of leukemia activity. Another explanation concerns a risk of CNS damage by low CSF-Cu causing neuron dysfunction. Conditions necessary for the interpretation of these results into a clinical strategy for followup study are outlined.

Child↗

PubMed1991

Changes of zinc values in children during malignant disease.

In 47 children with malignancy, zinc status, growth, and performance during standard treatment were compared with those in controls. At diagnosis, growth was retarded and hair zinc values were high, 2.4 +/- 0.7 mumol/g, as in chronic deficiency. During induction therapy, serum declined to 10.4 +/- 2.3 mumol/L and urinary excretion increased to 5.3 +/- 2.8 mumol/mol creatinine, as in acute exacerbation of deficiency. Control CSF values in children in remission, 0.04 +/- 0.01 mumol/L, were lower than reference values in adults. No difference in mean CSF zinc was observed during therapy, or in those with acute lymphoblastic leukemia (1) at high risk, (2) with central nervous system involvement, (3) with low performance, or (4) resistant to therapy. In six children unexplained values, up to 0.28 mumol/L during induction, were measured. No correlations between the various zinc parameters were found.

Adolescent↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

Dietary vitamin E deficiency and zinc metabolism.

In adult rats, the influence of vitamin E deficiency on zinc metabolism in general and specifically in 15 tissues was studied. After 50 days, we found evidence of vitamin E deficiency and at this time point we injected a tracer amount of 65Zn. During the next 18 days the zinc status was unaffected. The zinc metabolism, however, was altered: the apparent retention increased and the biological half life was prolonged. On day 68, the changes in various tissues varied. Some tissues were affected in zinc concentration (higher in plasma and spleen; lower in cerebrum, fur and tail), others in specific activity (higher in pancreas; lower in cerebellum). The different effects may reflect differences in tissue response on impairement, caused by vitamin E deficiency.

Animals↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1989

Clinical and laboratory diagnosis of acrodermatitis enteropathica.

Acrodermatitis enteropathica is an inborn error of metabolism resulting in zinc malabsorption and severe zinc deficiency. From personal experience and a literature review the following conclusions were drawn: 1. Symptoms other than dermatitis, vary with age. Diarrhoea, mood changes, anorexia, and neurological disturbance were reported most frequently in infancy. Growth retardation, alopecia, weight loss and recurrent infections were prevalent in toddlers and schoolchildren. Spontaneous remission may occur at adolescence. 2. The severity of symptoms also varies. Intermittent or mild cases of the disease and those presenting with uncommon features such as ophthalmic, cerebral or hepatic involvement, are easily overlooked. In the severe cases this may result in a fatal outcome. If untreated, the overall mortality rate is 20%, being higher in males. 3. The laboratory diagnosis is hazardous. In patients, mean zinc values in serum, urine and hair were ca. 50% of normal levels. There is a 15% overlap with healthy controls; moreover, low zinc levels in serum, urine or hair are also found in other diseases. A more specific test is required. 4. In cases of doubt, in vitro or in vivo zinc absorption tests using radioisotopes (65Zn or 69mZn) may be performed. These appear not to be influenced by other conditions and show less overlap with controls. If such tests are unavailable, the clinical response to 3-30 mumol zinc/kg per day for 5 days may be awaited. This is recommended in infants or children with one or more symptoms of acrodermatitis enteropathica.

Acrodermatitis↗

PubMed1989

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↗

PubMed1989

Clinical examination of weanling rats with early zinc deficiency.

In order to gain experience about the detection of adverse effects during a scientific procedure, we carried out a clinical examination of rats with zinc deficiency. In weanling rats fed a zinc-deficient diet (30 mumol zinc/kg) for 10 days, the mean tibial concentration of zinc was reduced by 53% and body weight gain by 73% when compared with rats fed a diet containing an adequate amount of zinc (150 mumol zinc/kg). In a small open field on day 9 of the experiment, the deficient rats more frequently displayed the posture standing upright with elevated heels. On day 10 of the experiment a clinical examination was carried out at random and 'blind' by three independent assessors. Out of 20 variables scored quantitatively on each individual animal, only body size differed between normal and deficient rats. Other classical signs of zinc deficiency, such as alopecia, dermatitis and diarrhoea, were not detected. It is concluded that in this rat model of zinc deficiency, no evidence for extreme discomfort can be demonstrated.

Animals↗

PubMedDate not supplied

Growth characteristics in laboratory animals fed zinc-deficient, copper-deficient, of histidine-supplemented diets.

The effects of growth in male Wistar rats and female Swiss Random mice were studied during dietary zinc (Zn) deficiency, copper (Cu) deficiency, and during the feeding of a histidine (His) supplement Growth was analyzed by comparing the characteristics of the decreasing exponential growth curve plotted for the experimental period. When the animals were pair-fed the experimental diets, the growth pattern in the animals remained unaltered. The growth rate decreased during Zn deficiency by a factor of 0.64 over a period of 10 d (male young adult rats) and by a factor of 0.76 over a period of 28 d (female weaning mice). On the other hand, a supplement of His increased the growth rate by a factor of 1.11 (in the mice). The effect of Cu deficiency on the growth rate was not statistically significant (in the rats). However, Cu deficiency causes effects in the Zn status that may over-compensate minor growth retardation during Cu deficiency. The effect of the His supplement is explained by its having an effect on the Zn-absorption (His enhancing Zn transport over the gut) and by a stimulating effect of this amino acid on the thickness of the growth plate in bone.

Animals↗

PubMedDate not supplied

Clinical and laboratory assessment of zinc deficiency in Dutch children. A review.

The clinical spectrum of acrodermatitis enteropathica (n = 226) is compared with symptoms reported in other Zn deficiencies: total parenteral nutrition without Zn (n = 21), protein energy malnutrition (n = 24), gastrointestinal disease (n = 79), geophagia (n = 227), and dietary low intake (n = 23). Common features of deficiency are diarrhea, recurrent infection, and growth retardation. Dermatitis is less common in other types of deficiency than in acrodermatitis enteropathica (9 vs 88% of cases). Anorexia and/or hypogeusia is reported more frequently in the other types of deficiency (30 vs 16%). The main symptoms in acrodermatitis enteropathica vary with age. These differences in the clinical picture of Zn deficiency are discussed in relation to the degree of the deficiency (acute, subacute, or chronic; severe, mild, or subclinical). The results of the conventional laboratory tests to diagnose Zn deficiency (Zn levels in serum, urine, or hair) are reviewed. In healthy Dutch infants and children, the mean values of these levels vary by a factor of 1.6-3.0. Also, the clinical interpretation of their results is prone to errors. Therefore, we advocate the erythrocytic 65Zn uptake test. Its mean varies by 1.3. However, its reference values for different age intervals need to be established. From the comparison of the results of three conventional tests of samples taken concurrently (serum, urine, and hair) in groups of Dutch children with symptoms common in Zn deficiency (diarrhea, recurrent infection, or growth retardation), it is estimated that +/- 1% of Dutch children with minor complaints suffer from either acute or subacute Zn deficiency. Other deficiencies occur occasionally. In order to detect the individual patient with deficiency, the erythrocytic 65Zn uptake test is promising and needs to be evaluated. Therefore, we review a set of reference laboratory tests with results that alter during sequential stages of overload and deficiency. Such a scheme is advocated as a guidance for future clinical research on deficiency, and solves the problem of differentiating those conditions that identify the individual patients who need treatment by supplementation.

Acrodermatitis↗

PubMedDate not supplied

Ascorbic acid supplementation and copper status in rats.

The effect of a high concentration (1%, w/w) of ascorbic acid in a Cu-adequate (150 mumol/kg) purified diet was studied in rats. After 6 wk, ascorbic acid had significantly reduced Cu concentrations in muscle and bone. The estimated whole body content of Cu in rats fed ascorbic acid was reduced by 20%. Within 1 d after oral administration of 64Cu, the recovery of the dose in feces was increased in rats fed ascorbic acid, suggesting that the vitamin depresses intestinal absorption of Cu. After intraperitoneal (ip) administration of 64Cu, the rate of loss of the dose from the body was decreased in rats fed ascorbic acid. This study suggests that the ascorbic acid induces a decreased efficiency of intestinal Cu absorption, which in turn triggers mechanisms to preserve Cu in the body stores. This is supported by the observation that the feeding of a Cu-deficient diet (5 mumol/kg) had similar effects, although more pronounced.

Animals↗