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Biomedical subjects

R Lauwerys

Publications and source records attributed to R Lauwerys.

At least 199 records · Page 11Linked to original sources

Study on in vivo and in vitro metabolism of dimethylformamide in male and female rats.

The study of dimethylformamide (DMF) metabolism by rat tissues in vitro indicates that formaldehyde is not a metabolic product as previously reported [1]. Furthermore, no other monocarbon derivative (CO, CH3OH, HCOOH, CH4) was detected when DMF was incubated with a fortified liver preparation. One metabolic product is methylhydroxymethylformamide (DMF-OH) measured as N-methylformamide (NMF) due to the breakdown of the hydroxymethyl group during gas chromatography. It was usually believed that the main metabolite excreted in urine following administration of DMF to male and female rats was NMF. The results of this study indicate that DMF-OH constitutes the main metabolite in vivo. A quantitatively less important urinary metabolite, hydroxymethylformamide (NMF-OH), is determined as formamide (F) by gas chromatography. In male and female rats, partial hepatectomy reduces markedly the in vivo biotransformation of DMF. Following administration of DMF or NMF, the total amount of metabolites (DMF-OH and/or NMF-OH) excreted in urine is identical in both sexes, but female rats excrete more unchanged parent compound than male rats. The rate of NMF-OH excretion in urine following high doses of DMF supports the hypothesis that DMF may inhibit its own biotransformation.

Aminopyrine↗

Anti-laminin antibodies in Sprague-Dawley and brown Norway rats chronically exposed to cadmium.

Sprague-Dawley and Brown-Norway female rats were chronically exposed to cadmium. The metal was administered either in drinking water at a concentration of 20 or 100 ppm for 13 months or intraperitoneally (i.p.) at the dose of 1 mg/kg, 5 times a week for 4 months. Anti-laminin and anti-type IV procollagen antibodies (laminin and type IV procollagen are components of the glomerular basement membranes) were sequentially assessed by radioimmunoassay in serial serum samples. Anti-type IV procollagen antibodies were never detectable whereas anti-laminin antibodies were transiently found in the serum of Sprague-Dawley rats only. In the i.p. group, the antibodies were detected between week 4 and 8, whereas in the oral treatment group, they were detected between month 6 and 8. At the same time, the concentration of cadmium in kidney cortex averaged about 100 ppm in the 20 ppm cadmium group and about 200 ppm in the 2 other treatment groups. The pathogenic significance of these antibodies in chronic cadmium intoxication of Sprague-Dawley rats remains to be assessed since their occurrence was not associated with concomitant immunoglobulin deposits in the kidneys.

Animals↗

Environmental pollution by cadmium and cadmium body burden: an autopsy study.

The industrial area of Liège in Belgium is polluted by cadmium mainly because of past emission from non-ferrous metal industries. Persons who have lived in that area have accumulated significantly more cadmium in the renal cortex and in the liver than those who have resided in other regions of the country.

Belgium↗

In vitro effects of lead, mercury and cadmium on the enzymic activity of red-blood cell pyrimidine 5'-nucleotidase.

The decrease of pyrimidine 5'-nucleotidase (P5N) in human erythrocytes, detected in persons occupationally exposed to lead (Pb), is not an in vitro artefact resulting from the release of lead during erythrocyte hemolysis but is a true reflection of the enzyme activity in vivo. Like Pb, mercury (Hg) and cadmium (Cd) ions exhibit an important in vitro inhibitory action on the P5N enzymic activity. However, when the metals are preincubated as metallothionein complexes with P5N preparations, their inhibitory power disappears.

5'-Nucleotidase↗

Distal tubular dysfunction in rats chronically exposed to a 'white spirit' solvent.

Inhalation exposure of male Sprague-Dawley rats to an industrial white-spirit solvent composed of a C10-C12 mixture of branched-chain unsubstituted satured aliphatic hydrocarbons at 6500 mg/m3 for over 9 months resulted in decreased urinary concentrating ability, decreased net acid excretion following a mild ammonium chloride load and increased urinary lactate dehydrogenase (LDH) activity, whereas urinary beta-N-acetyl-D-glycosaminidase (NAG) activity remained normal. These observations suggest the existence of distal tubular alteration in the rat kidney.

Acetylglucosaminidase↗

Urinary cadmium and lead concentrations and their relation to blood pressure in a population with low exposure.

The 24 hour urinary excretion of cadmium (U-Cd) and lead (U-Pb), and the excretion of beta-2- microglobulins and retinol binding protein concentration in spot urines, were determined in a random 4% sample of the population of a small Belgian town. Blood pressure and body weight were measured on two separate occasions. U-Cd averaged 2.4 nmol/24 h in 46 youths, increased with age, and was significantly higher in 57 adult men as compared with 59 women (9.3 v 7.2 nmol/24 h; p less than 0.01). U-Pb averaged 28 nmol/24 h in youths and similarly increased with age: adult men excreted more lead than women (64 v 40.0 nmol/24 h; p less than 0.001). Among men, manual workers excreted more cadmium (12.6 v 7.5 nmol/24 h; p less than 0.05) but a similar amount of lead (62 v 61 nmol/24 h) compared with office workers. After adjusting for sex and age, U-Cd and U-Pb were not related to body weight and cigarette consumption. In simple regression analysis, U-Cd was positively correlated with both systolic (r = +0.30; p less than 0.05) and diastolic (r = +0.38; p less than 0.01) blood pressure in women. After adjusting for other contributing variables, however, a weak but negative relation became apparent between systolic pressure and U-Cd in women (t = -2.21; p = 0.033) and between diastolic pressure and U-Cd in men (t = -2.04; p = 0.047). In women urinary beta-2-microglobulin was related to diastolic pressure (r-0.44; p<0.01) and after adjusting for age to both systolic (t=2.75; p=0.009) and diastolic (t=-3.07; p=0.004) pressure. In none of the sex-age groups did U-Pb and retinol binding protein contribute to the blood pressure variability.

Adolescent↗

Acute diquat intoxication. Interest of its repeated determination in urine and the evaluation of renal proximal tubule integrity.

A 33-year old farmer ingested approximately 300 ml of a 20% solution of diquat along with about 80 mg flunitrazepam. The patient presented neurological (coma grade I), digestive (oro-pharyngeal erosions, ileus), hepatic (cytolysis), hematological (thrombopenia) and renal (tubular dysfunction) signs. Plasma creatinine did not exceed 1.22 mg/dl (upper normal value), but retinol binding protein level in urine (a marker of renal tubular dysfunction) reached a value of 337 mg/d (normal values less than 300 micrograms/d). Its level returned to normal value 18 days after the ingestion. Four hours after the poisoning, diquat level in blood amounted to 10.4 mg/l, but its level was below the detection limit (0.2 mg/l) 6 hours later. In urine, however, diquat was detected until day 13. The following therapy was applied: ventilation (FiO2:0.21), gastro-intestinal lavage, hemoperfusion, anti-oxidants and prolonged forced diuresis. The patient made an uneventful recovery. intestinal washout must be applied with caution since an ileus is a classical complication of diquat poisoning. Hemoperfusion was found to be of little value. The interest of prolonged application of forced diuresis is suggested by the detection of diquat in urine for about 2 weeks along with the presence of biological signs of renal tubular dysfunction.

Adult↗

Basic concepts of monitoring human exposure.

Environmental and biological monitoring are two complementary approaches for evaluating human exposure to genotoxic agents. Environmental monitoring involves, usually, measurement of chemicals either by physico-chemical techniques or via biological activities (e.g., mutagenic activity of airborne pollutants). Biological monitoring relies on two groups of tests: those based on determination of the substances or their biotransformation products in various biological media and those based on detection and, possibly, quantification of those biological changes that result from the reaction of the organism to exposure. The application of tests for exposure and the interpretation of the results require a careful evaluation of several issues, mainly the sensitivity, specificity and health significance of the selected monitoring parameters, the precision and accuracy of the analytical technique and the ethical aspects.

Biotransformation↗

Health surveillance of workers exposed to tetrachloroethylene in dry-cleaning shops.

Behavioral, renal, hepatic and pulmonary tests were applied to 22 subjects exposed to tetrachloroethylene in 6 dry-cleaning shops. The results were compared with those obtained in 33 subjects non-occupationally exposed to organic solvents. The intensity of exposure was monitored by personal environmental monitoring and by urine analysis for trichloroacetic acid and expired air and venous blood analysis for tetrachloroethylene. The time-weighted average exposure to tetrachloroethylene amounted to 21 ppm (range 9 to 38 ppm). The correlation between the concentration of tetrachloroethylene in ambient air sampled with the charcoal tube method and with a passive dosimeter indicates that the latter can correctly estimate the time-weighted average exposure to the solvent. In view of the long biological half-life of tetrachloroethylene, the internal dose may be better estimated by measuring its concentration in blood 16 h after the end of exposure (i.e. before resuming work the next morning). The present study suggests that if the blood concentration of tetrachloroethylene does not exceed 1 mg/l, 16 h after the end of exposure, the time-weighted average exposure is likely to have been below 50 ppm. Exposure to such level for 6 years on the average does not seem to exert any adverse effect on the central nervous system, the liver and the kidney.

Adolescent↗

Significance of urinary metallothionein in workers exposed to cadmium.

Cadmium in blood (Cd-B) and in urine (Cd-U) and metallothionein (Mt-U) and beta 2-microglobulin in urine (beta 2m-U) were measured in 94 male Cd workers. The results were examined according to the workers' current exposure to cadmium (group C, n = 73, workers currently exposed to Cd; group R, n = 21, Cd workers removed from exposure or retired) and according to their renal status (group N, n = 66, normal beta 2m-U; group I, n = 28, beta 2m-U greater than 200 micrograms/g creatinine). The interrelationships between Mt-U, Cd-U, Cd-B and years of cadmium exposure were examined in the various subgroups. The study of the correlations between these variables demonstrates that Mt-U is directly correlated with Cd-U but not with Cd-B or years of Cd exposure. The association between Cd-U and Mt-U is independent of the status of renal function and the intensity of current exposure to cadmium. Under moderate chronic exposure to cadmium, the fraction of Cd-U which is directly influenced by recent exposure (Cd-B) is small in comparison with that influenced by the cadmium body burden.

Adult↗

Renal handling of human beta 2-microglobulin in normal and cadmium-poisoned rats.

The renal handling of human beta 2-microglobulin (beta 2-m) was investigated in normal rat and in rat with cadmium-induced renal damage. Cadmium was administered either in drinking water at a concentration of 100 ppm for up to 16 months or by i.p. injection of 1 mg Cd/kg, five times a week for up to 4 months. When renal dysfunction has developed, namely after 2 and 10 months of the i.p. and oral treatment respectively, unlabelled human beta 2-m was injected intravenously and its disappearance in serum and its urinary excretion were studied by means of a sensitive immunoassay. In serum, the level of beta 2-m drops by about 90% during the 10 first min, then declines more slowly with a half life around 20 min. Serum disappearance curves of beta 2-m in normal and cadmium-treated rats did not differ markedly. The amount of beta 2-m recovered in urine during the 4 h following the injection averaged 0.03% of the injected dose in normal rats. It increased on the average to 10% in rats treated i.p. with 1 mg Cd/kg for 3 months. However, in rats given 100 ppm Cd per os for 10 months, this amount averaged only 0.14%. A similar value was observed 5 months later, although at that stage, the critical level of cadmium in kidney cortex had been reached for 6-7 months. These data which were in accordance with the disturbances of the other renal parameters measured in cadmium-treated rats indicate that: 1) human beta 2-m is reabsorbed by rat kidney at a similar rate as by human kidney; 2) if the occurrence of cadmium tubulopathy is concomitant with the saturation of cadmium-binding sites in kidney, its severity depends greatly on the rate at which cadmium reaches the saturated kidneys.

Animals↗

Oral daily intake of cadmium, lead, manganese, copper, chromium, mercury, calcium, zinc and arsenic in Belgium: a duplicate meal study.

One hundred and twenty four daily meals collected in three areas of Belgium were analysed for their content of several metals. The following median values for 24-hr intakes were found: cadmium, 15 micrograms; lead, 95.7 micrograms; manganese, 2.6 mg; copper, 1.3 mg; chromium, 0.24 mg; mercury, 6.5 micrograms; calcium, 541 mg; zinc, 13.2 mg; arsenic, 11.5 micrograms. The distributions of the individual results suggest that about 1-2% of the daily meals sampled had mercury and cadmium contents that exceeded the tolerable level proposed by WHO; in the case of lead this level was exceeded in 10%.

Arsenic↗

Anti-laminin antibodies in workers exposed to mercury vapour.

In 62 male workers exposed to mercury vapour for 5.5 years on average, the results of several renal parameters were not significantly different from those found in a well-matched control group (n = 60). Circulating anti-laminin antibodies were found, however, in 8 workers exposed to mercury vapour but in none of the control workers. These results suggest that occupational exposure to mercury vapour may lead to immune dysfunction in a certain percentage of the exposed population. Whether such a finding is predictive of the occurrence of an immune glomerulonephritis remains to be evaluated.

Antibodies↗

The critical level of cadmium in human renal cortex: a reevaluation.

The previously published estimate (160 ppm) of the critical level of renal cortical cadmium (Cd) (Roels et al., Environ. Res., 26 (1981) 217-240) has been reassessed after the depth of the left kidney was measured in each worker by echography. The correction introduced for kidney depth demonstrates that the critical liver cadmium level of 30 ppm corresponds to a corrected critical level of cadmium in renal cortex of 216 ppm. This critical cadmium level in renal cortex (CdKc) protects probably more than 90% of male workers from developing Cd-induced renal dysfunction.

Cadmium↗

The influence of orally-administered vitamin C or zinc on the absorption of and the biological response to lead.

A single-blind study was performed on male workers from a primary lead smelter to determine whether a daily oral supplement of vitamin C (1 g vitamin C orally once a day, five times a week for 20 weeks) or zinc (60 mg zinc as zinc gluconate once a day, five times a week for eight weeks) influences the absorption of and the biological (hematological and renal) response to lead. The vitamin C and the zinc study groups comprised 39 and 11 workers, respectively. Their blood levels of lead at the start of the experiment ranged from 28.9 to 76.4 micrograms/100 ml. A matched control group receiving a placebo was followed simultaneously. The results demonstrate that, in workers whose exposure to inorganic lead is moderate and who do not suffer from nutritional deficiencies, oral supplementation of vitamin C or zinc does not influence the metabolism and biological action of lead.

Absorption↗

Latex immunoassay of urinary albumin.

A new non isotopic immunoassay based on latex particle agglutination has been developed for the determination of albumin in urine. The assay consists in incubating the urine sample for 30 min at 37 degrees C with latex particles coated with a specific antibody, followed by quantification of the resulting agglutination by particle counting or turbidimetry. The stability of antibody-coated particles during incubation is achieved by diluting them just before the assay in a buffer containing bovine serum albumin. The pH of this buffer, the antibody loading and the concentration of latex particles in the incubation mixture were optimized to obtain the maximal specific and minimal nonspecific agglutination. The albumin standard curve ranges from 25 to 800 micrograms/l. Reproducibility tests performed within and between run gave CV's ranging from 8.2 to 11.6%. The recovery of albumin added to 10 urines averaged 95.5%. A correlation coefficient of 0.96 was obtained between latex immunoassay and nephelometry for the determination of albumin in 51 urines.

Adult↗