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Biomedical subjects

R Lauwerys

Publications and source records attributed to R Lauwerys.

At least 163 records · Page 9Linked to original sources
PubMed1987

Metal-induced alterations of delta-aminolevulinic acid dehydratase.

ALAD is a cytoplasmic enzyme that catalyzes the second step of the heme biosynthesis pathway, that is, the condensation of two molecules of delta-aminolevulinic acid into porphobilinogen. ALAD is a zinc-dependent enzyme; thiol groups are essential for its activity; and in vitro experiments show that ALAD can be activated or inhibited by several metal ions including A;3+, Pb2+, Cd2+, Hg2+, Ag2+, and Cu2+. To explain these effects, it has been postulated that metals bind to thiol groups of allosteric sites and, according to their structure, provoke allosteric transitions to the active or inactive form of the enzyme. Under current environmental and occupational exposure levels, lead is practically the only metal that can affect ALAD activity. Erythrocyte ALAD is the most sensitive indicator of lead exposure: effects of exposure are detectable even when blood lead levels are within the "normal" range. Zinc protects ALAD in vitro and in vivo from the inhibitory effect of lead. There is also some suggestion that aluminum could be responsible for the decreased erythrocyte ALAD activity observed in patients on chronic hemodialysis.

Aluminum↗
PubMed1987

Competition between low- and high-molecular-weight proteins for renal tubular uptake.

To explain the occurrence of tubular and glomerular proteinuria in patients with primarily tubular or glomerular dysfunction, it is usually assumed that the mechanisms responsible for the renal tubular transport of small and large proteins are different. The present in vivo study does not support this hypothesis since it clearly shows that small and large proteins (e.g., beta 2-microglobulin and albumin) can compete for renal uptake. Our results lead us to postulate the existence of common tubular reabsorption sites for which proteins exhibit different affinities depending on their charge, size and conformation.

Animals↗
PubMed1987

Effect of aluminum on porphyrin metabolism in hemodialyzed patients.

In patients with renal failure and on chronic hemodialysis, serum aluminum, serum delta-aminolevulinic acid, serum porphobilinogen and erythrocyte zinc protoporphyrin (ZPP) are significantly elevated, whereas erythrocyte delta-aminolevulinic acid dehydratase activity (ALAD, values in percent) is significantly reduced. The last two parameters (ZPP and ALAD) are statistically related to serum aluminum concentration (Al-S), but only the correlation between Al-S and ALAD remains statistically significant after standardization for the degree of renal insufficiency (expressed in terms of urea level). This study does not support the hypothesis that the retention of aluminum is responsible for the increase of ZPP in uremic patients on dialysis. The disturbances of porphyrin metabolism found in patients with renal failure and on chronic dialysis are not similar to those observed in porphyria cutanea tarda.

Adult↗
PubMed1987

Prenatal and early postnatal intoxication by inorganic mercury resulting from the maternal use of mercury containing soap.

A case of slight renal tubular dysfunction associated with cataract and anaemia was diagnosed in a 3-month-old black boy in whom high levels of mercury were found in blood and urine. Several arguments suggest that the renal, ocular and haematological defects may have resulted from exposure to mercury during foetal life and the 1-month lactation period due to the extensive use of inorganic mercury containing cosmetics by the mother.

Anemia↗
PubMed1987

Determination of IgE complexes and of total IgE by latex immunoassay.

A sensitive immunoassay based on latex particle agglutination for the measurement of circulating IgE-containing complexes is described. In this method, the anti-IgE-coated particles are incubated with diluted serum and the resulting agglutination is quantified by turbidimetry or particle counting. In the latter version, the assay is fully automated in a continuous flow system. IgE-containing complexes were detected in all tested sera. Increased concentrations were observed in about 80% of the subjects with elevated serum IgE. However, high levels of IgE-complexes may also be found in subjects with a normal or even a very low serum concentration of IgE. The same latex immunoassay can be used for the determination of total IgE, after pepsin digestion of the gamma-globulin fraction of the serum. The results obtained correlate well with those found with a sandwich radioimmunoassay (r = 0.91, n = 83). The present method, however, yields a greater number of significantly positive results than the radioimmunoassay, probably because of its ability to detect IgE entrapped in circulating complexes.

Antigen-Antibody Complex↗
PubMed1987

[Demonstration of anti-laminin antibodies in the serum of healthy subjects].

Antibodies directed against laminin, a glycoprotein of basement membranes, have been sought for in the sera of 347 healthy subjects by a method relying on the agglutination of laminin-coated latex particles. Fifty-five subjects (15.9%) hae been found to be positive, 37 with a titre of 2, 14 with a titre of 4 and 4 with a titer of 8. Applied to 106 patients whose a renal biopsy had been examined by immunofluorescence, the test yielded positive results in 91% of patients with linear deposits as compared to 10.3 and 15.4% respectively in patients presenting with and without granular deposits along the glomerular basement membrane. The titers in anti-laminin antibodies observed in these patients ranged from 2 to 8. The discovery of circulating anti-laminin antibodies in serum from subjects without clinical or subclinical sign of renal impairment rises several questions regarding the pathogenicity of these auto-antibodies and their possible association with genetic or environmental factors.

Anti-Glomerular Basement Membrane Disease↗
PubMed1987

[Lipid peroxidation in human pathology: evaluation of data in literature].

Several methods have been proposed for detecting the oxidation and breakdown of polyunsaturated fatty acids (lipoperoxidation process) in humans. The lipoperoxidation products which hitherto have been measured in sufficiently large groups of subjects are lipid conjugated dienes, malonic dialdehyde and fluorescent byproducts in biological fluids and low molecular weight aliphatic hydrocarbons in expired air. None of these methods can yet be considered as the method of choice. Various analytical pitfalls and several epidemiological and statistical biases cast doubt about the conclusions of the majority of the studies carried out so far in humans. Provided further studies are undertaken to determine the factors which influence the metabolism of low molecular weight hydrocarbons in man, expired air analysis might constitute a practical and promising in vivo approach for detecting an increased lipoperoxidation process.

Fatty Acids, Unsaturated↗
PubMed1986

Determination of rat beta 2-microglobulin in urine and in serum. I. Development of an immunoassay based on latex particles agglutination.

Rat beta 2-microglobulin has been isolated from the urine of rats pretreated with sodium chromate. The purified protein was used to raise antisera in two rabbits. Treatment of the antisera with ammonium sulphate followed by gel chromatography led to an immunoglobulin fraction which was used to coat latex particles by physical adsorption. The latex suspension was used in an automated system including an optical particle counter to analyse the protein in serum, urine and cerebrospinal fluid. Serum contains 5.8 mg of beta 2-microglobulin/l, of which 33% is found as a 55000 dalton complex while 66% is present as the 'free' protein. The daily urinary excretion of beta 2-microglobulin in females is about 2 micrograms of which 7% is found to be a 65000-dalton complex while 92% is the free protein. From this, it can be calculated that the fractional urinary excretion of beta 2-microglobulin is about 0.03%. The cerebrospinal fluid contains about 1 mg of beta 2-microglobulin/l. Preliminary tests also suggest that the method can be adapted for non-automated turbidimetric detection. In the automated assay, the within- and between-assay coefficients of variation are less than 10% for the three biological fluids tested. The analytical recovery in the urine is 93%. In urine, beta 2-microglobulin undergoes proteolytic degradation at pH below 6. This does not represent a serious drawback to its use as a sensitive index of tubular function since in most experimental circumstances, rats excrete urine with a pH above this value.

Animals↗
PubMed1986

Determination of rat beta 2-microglobulin in urine and in serum. II. Application of its urinary measurement to selected nephrotoxicity models.

beta 2-microglobulin (beta 2-m) was measured in the urine of rats by a specific immunoassay based on latex particles agglutination. The excretion of this protein was compared to the excretion of the enzyme beta-N-acetyl-D-glucosaminidase (NAG), albumin and amino acids in rats treated with either a single dose of sodium chromate (5 and 10 mg kg-1), repeated doses of gentamicin (5 and 20 mg kg-1), or cadmium (1 mg kg-1), and in aging rats (from 2 to 20 months). All treatments resulted in an early increased excretion of beta 2-m indicative of functional alterations of the proximal tubular cells. An increased NAG excretion was observed only at the highest dose of chromate and in the cadmium model but the relative increases of beta 2-m were much larger (up to 200 times the control values against four times the control values for NAG). From 2 to 20 months of age, urinary beta 2-m increases by a factor of four. Aminoacids excretion showed little sensitivity in the various models. Albumin showed little variations in purely tubular or in the tubular phase of renal injury but the chronic progressive nephrosis of aging rats caused a 40-fold increase in its excretion between 2 and 20 months of age. Therefore urinary beta 2-m, albumin and albumin/beta 2-m ratio provide useful tools in the assessment of nephrotoxicity and of its mechanisms in various experimental models.

Acetylglucosaminidase↗
PubMed1986

Influence of manganese on the gastrointestinal absorption of cadmium in rats.

Four groups of male rats were given the following oral treatment: control group (n = 20) deionized drinking water, Mn group (n = 20) deionized drinking water containing 56 ppm Mn2+ (1 mmol/l), Cd group (n = 10) deionized drinking water containing 112 ppm Cd2+ (1 mmol/l) and Cd + Mn group (n = 10) deionized drinking water containing 112 ppm Cd2+ and 56 ppm Mn2+. Half of each group was sacrificed after 4 weeks and the other half after 8 weeks of treatment. At each time interval, the mean levels of Mn in blood, in urine and in the various tissues did not differ between the control and Mn groups. Furthermore, comparable Mn levels were found after 4 and 8 weeks of treatment. Microscopical examination of the brain failed to reveal any overt morphological alteration in the Mn group. With respect to the control group, the Cd and Cd + Mn groups exhibited increased levels of Cd in blood, urine, liver, whole kidney, kidney cortex and in brain (cortex, cerebellum, basal ganglia), but the Cd + Mn groups showed invariably lower levels than the Cd group after 4 weeks as well as after 8 weeks. These results suggest that the rate of gastrointestinal absorption of Cd is decreased by supplementation of the drinking water with a 'non-toxic' dose of Mn2+.

Animals↗
PubMed1986

Yellow mercuric oxide ointment and mercury intoxication.

Repeated cutaneous application of yellow mercuric oxide ointment for infected eczema resulted in mercury poisoning in a 4-month-old infant. Toxic levels of mercury were measured in blood, urine, cerebrospinal fluid and tissues.

Administration, Topical↗
PubMed1986

Effects of gentamicin on the renal uptake of endogenous and exogenous protein in conscious rats.

To study the effect of gentamicin on the renal uptake of proteins, Sprague-Dawley female rats were intravenously injected with solutions containing unlabeled human beta 2-microglobulin (beta 2-m), retinol-binding protein, and increasing amounts of gentamicin (from 0.063 up to 31.5 mg/kg). The concentrations of human proteins and that of endogenous beta 2-m, albumin, and IgG in the urine collected during the 2 hr following the injection were determined by immunoassays. Gentamicin transiently increased the urinary excretion of rat and human beta 2-m in a dose-dependent manner. The mean relative increase of rat beta 2-m excretion ranged from 2 at a gentamicin dose of 0.06 mg/kg up to 500 at a gentamicin dose of 31.5 mg/kg. By contrast, the urinary excretion of other proteins was only increased by a factor of 2 to 5 at the highest dose of gentamicin. The relative increase of the urinary excretion of proteins was positively correlated with the fractional reabsorption of the proteins by the rat kidney. The inhibitory effect of gentamicin on the renal uptake of protein was very similar to that observed in rats injected with polycationic proteins like lysozyme and cytochrome C. These observations, combined with the fact that gentamicin, like proteins, enters the tubular cell by adsorptive endocytosis, strongly suggest that this drug competes with proteins for common binding sites on the apical tubular membrane and for subsequent endocytosis. Furthermore, the iv injection of large amounts of gentamicin and polycationic proteins induces a lysosomal enzymuria which very likely is a manifestation of an increased exocytosis.

Animals↗
PubMed1986

Isoparaffinic solvent-induced nephrotoxicity in the rat.

Prolonged inhalation exposure to 6.5 mg/l of an isoparaffinic solvent consisting of saturated aliphatic hydrocarbons (SAHC) resulted in both functional and morphological renal changes in male rats to the exclusion of female or castrated rats. Functionally, the increased excretion of lactate dehydrogenase in the absence of an increased beta-N-acetyl-D-glucosaminidase excretion together with a decreased urinary concentrating ability upon water deprivation and slower antinatriuretic response when the sodium intake is abruptly reduced, suggest a distal tubular alteration. beta 2-Microglobulin excretion is unchanged indicating good proximal tubular cell function. The increased excretion of albumin and slightly lowered glomerular filtration rate suggest a moderate glomerular impairment. Light microscopy shows prominent hyaline droplet accumulation in proximal tubular cells and a few scattered foci of regenerative epithelia in both proximal and distal cells of the deep cortex. The urinary clearance of the major male rat urinary protein, alpha 2u-globulin, is similar in control and exposed rats but the latter have a 10-fold greater renal accumulation of this protein while the hepatic levels are identical in both groups. It is concluded that SAHC exposure causes moderate and reversible tubular and also glomerular changes in the male rat kidney.

Acetylglucosaminidase↗
PubMed1986

Present status and trends in biological monitoring of exposure to industrial chemicals.

This paper describes the current practice of biological monitoring of populations exposed to occupational or environmental pollutants. The three types of monitoring are ambient monitoring, biological monitoring of exposure, and health surveillance (also called biological monitoring of effects). The trend in biological monitoring today is to develop tests that provide information on the amount of chemical bound to the critical sites of action (target dose). Ambient monitoring and biological monitoring assess the health risk by comparing the current exposure with the permissible exposure limits. They are essentially preventive activities. By contrast, health surveillance or biological monitoring of effects assesses the health status and aims at detecting the early adverse health effects. Health surveillance is part of the medical screening program for the early detection of health impairment due to industrial chemicals.

Environmental Exposure↗