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Biomedical subjects

R Lauwerys

Publications and source records attributed to R Lauwerys.

At least 127 records · Page 7Linked to original sources
PubMed1990

Acute polyneuropathy after malathion poisoning.

We report a patient in whom intoxication with a commercial preparation of malathion led to a severe acute cholinergic crisis, protracted cardiac arrhythmias, an acute respiratory distress syndrome, and an acute sensorimotor axonal polyneuropathy. The occurrence of the polyneuropathy was associated with a novel malathion transformation product, S-(1-ethoxycarbonyl, 2-isopropoxycarbonyl) ethyl 0,0-dimethyl phosphorodithioate (isopropylmalathion), an impurity present in the pesticide residue. The role of isopropylmalathion in the pathophysiology of the polyneuropathy remains to be determined.

Acetylcholinesterase↗
PubMed1989

In vitro and in vivo effect of mercury, lead and cadmium on the generation of chemiluminescence by human whole blood.

A method based on the use of the luminogenic substance, luminol, was developed for measuring the respiratory burst induced by phorbolmyristate acetate in 4 microliters of human whole blood. In vitro, the three cations, Hg2+, Pb2+ and Cd2+, inhibit the peak luminescence response at concentrations higher than those usually found in blood of subjects exposed to these metals. Cadmium metallothionein, however, in a concentration range similar to that found in whole blood of workers exposed to cadmium strikingly reduces the respiratory oxidative burst. In workers exposed to inorganic lead or mercury vapour, no reduction of the chemiluminescence response of whole blood was observed while a slight but statistically significant reduction was found in whole blood from cadmium exposed workers. If a similar effect occurs in lung macrophages, it might decrease the respiratory tract resistance to infection.

Adult↗
PubMed1989

Comparison of the effects of auranofin and retinoic acid on plasminogen activator activity of peritoneal macrophages and Lewis lung carcinoma cells.

Urokinase-type plasminogen activator, a neutral proteinase, seems to play a central role in the degradation of the extracellular matrix that accompanies a number of biological phenomena including inflammatory reactions and neoplasia. The effect of auranofin and retinoic acid on the plasminogen activator activity expressed by two cell types, i.e. murine macrophages and Lewis lung carcinoma cells, has been investigated. Low concentrations of both drugs (10(-6)-10(-7) M) can inhibit in vitro the induction of plasminogen activator in macrophages stimulated by phorbol 12-myristate 13-acetate. This action occurs rapidly (15 min), is irreversible and is independent of a global cytotoxic effect. Auranofin and retinoic acid remain without effect in macrophages when added after stimulation by the phorbol ester. Both drugs are thus potent inhibitors of the induction of plasminogen activator activity in macrophages, possibly through an interaction with the protein kinase C system. The plasminogen activator activity of Lewis lung carcinoma cells, which is apparently not dependent on a protein kinase C pathway, is not influenced by auranofin or retinoic acid. These observations may contribute to explain: (1) the activity of auranofin and retinoic acid in rheumatoid arthritis, and (2) the antitumor promoting activity of retinoic acid. It would be relevant to assess whether auranofin may exhibit, like retinoic acid, an antitumor-promoting activity.

Animals↗
PubMed1989

Lipid peroxidation in acrylonitrile-treated rats, evidenced by elevated ethane production.

The intraperitoneal administration of acrylonitrile (greater than 25 mg kg-1) to rats is associated with an increased production of ethane and a rise of the serum activity of the cytosolic enzyme, sorbitol dehydrogenase. These effects are prevented by pretreatment with vitamin E and the microsomal enzyme inhibitor SKF 525A, but are exacerbated by pretreatment with the microsomal enzyme inducer, phenobarbital. Repeated intraperitoneal administration of acrylonitrile (40 mg kg-1) for four weeks also increases ethane production and serum SDH activity, and produces various morphological changes in liver parenchymal cells (necrosis, increased mitotic activity, increased nucleolar size and myelinic figures in mitochondria) and inhibits the growth of the animals. All these effects are prevented by the administration of vitamin E (190 mg kg-1 i.p., daily) during the last two weeks of treatment. A dose of sodium cyanide (2.5 mg kg-1 i.p.) which leads to a urinary excretion of thiocyanate similar to that found after the intraperitoneal administration of 25 mg kg-1 acrylonitrile, does not stimulate ethane production. This study suggests that the hepatoxicity of acrylonitrile may, at least partly, result from a lipoperoxidation process and is linked with its microsomal oxidative biotransformation.

Acrylonitrile↗
PubMed1989

Dose-related proximal tubular dysfunction in male rats chronically exposed to lead.

Male Wistar rats were given 0.5 and 2% lead acetate in drinking water for 2 months, 1% lead acetate for 3 months and sodium acetate equimolar to 2% lead acetate for 3 months. Glucose, total proteins, lactate dehydrogenase (LDH), lysozyme and beta 2-microglobulin (beta 2-m) were measured in 24-h urine every month. Kidney weight and histology were also examined. At the three doses, lead exposure produced a significant elevation of the kidney weight. No significant change in urinary parameters was observed in rats given 0.5% lead acetate. Exposure to 1% lead acetate increased the urinary excretion of beta 2-m only. At the 2% lead acetate dose the elevation of beta 2-m excretion was accompanied by an increased urinary output of glucose, total proteins, lysozyme and LDH. Observations of the kidneys by light microscopy were in agreement with these biochemical findings. The nephrotoxic effect of acetate was excluded by the lack of biochemical or histological effects of sodium acetate on the kidney. It is concluded that a proximal tubular dysfunction is induced in rats chronically exposed to high doses of lead.

Animals↗
PubMed1989

Preclinical detection of nephrotoxicity: description of the tests and appraisal of their health significance.

The prevention of renal diseases induced by chemicals requires the use of tests with which adverse renal effects can be detected at a stage when removal from exposure to the offending agent(s) may lead to complete recovery or may at least prevent an accelerated decline in renal function. The screening tests used in clinical medicine for assessing the functional integrity of the kidney are not sufficiently sensitive to attain this objective. In this review, we describe the tests currently available for detecting incipient renal damage and attempt to assess their health significance. A minimal battery of tests is recommended for the detection of groups in industry or in the general population who are at risk. If an increased prevalence of abnormal values for these parameters is found repeatedly in a population, efforts should be made to identify the causal agent(s) and, if possible, to reduce the exposure. Follow-up examinations of subjects identified in this way are also indicated, in order to define the predictive value of the detected changes better.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1989

Epidemiological application of early markers of nephrotoxicity.

This paper is a review of epidemiological studies in which sensitive markers of nephrotoxicity have been used to detect the early effects of chemicals on the kidney. Most of the studies are cross-sectional, and their objective was either to identify potentially nephrotoxic chemicals (organic solvents, heavy metals) in the working or general environment or to establish dose-response/effect relationships from which safe exposure levels can be defined (e.g., for cadmium and mercury vapour). A few longitudinal studies were conducted to determine the persistence of renal disturbances and to get information on their predictive value (e.g., microproteinuria in cadmium workers). Nephrotoxicity tests, which have proved to be the most useful in these epidemiological studies, rely on the determination of specific urinary proteins which, according to their size, reflect the functional integrity of the proximal tubule (e.g., retinol-binding protein or beta 2-microglobulin) or the glomerulus (e.g., albumin, immunoglobulin G). An increased urinary excretion of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase has been reported in several studies (e.g., in lead-exposed workers), but the pathological significance of this finding remains to be clarified, particularly when it is not associated with changes in the urinary excretion of specific proteins. Further work is needed to assess the usefulness of tests introduced more recently such as the assay of renal antigens in urine and the use of red-blood-cell membrane negative charges as an index of the glomerular polyanion. With the exception of microproteinuria observed in chronic cadmium poisoning, no epidemiological data are available on the prognostic value of subclinical renal effects caused by nephrotoxic chemicals.

Biomarkers↗
PubMed1989

Detection of hand tremor in workers exposed to mercury vapor: a comparative study of three methods.

Hand tremor measurement was evaluated in a group of 54 male workers (mean age 38.5 years) exposed to mercury vapor (average duration of exposure 7.7 years) using an accelerometer test and two psychomotor tests (eye-hand coordination and hand steadiness). The results were compared with those obtained in a well-matched control group of 48 workers. The intensity of current mercury vapor exposure was rather moderate as reflected by the mean (geometric) levels of mercury in blood (2.4 micrograms/dl) and in urine (63 micrograms/g creatinine). The hand steadiness test and eye-hand coordination test revealed preclinical alterations in postural and intentional tremor, whereas the changes evidenced by the accelerometer test were not statistically significant. Furthermore the practical advantage of the psychomotor tests over the accelerometer test makes them most appropriate for the early detection of mercury-induced hand tremor. The present study also suggests that young adults (less than 21 years) may be more susceptible to the neurotoxic effect of mercury vapor.

Adult↗
PubMed1989

Predictors of methanol intoxication with unfavourable outcome.

In 10 adult patients acutely intoxicated with methanol, the base deficit and the total blood CO2 were highly correlated with blood formate level. No correlation was found between the same parameters and blood methanol level. Formate production is the main cause of acidosis in the early stages of methanol poisoning. The association of a latency period before treatment exceeding 10 hours and a blood formate level above 0.5 g/l (11.1 mmol/l) is predictive of severe methanol poisoning possibly leading to permanent sequelae.

Acidosis↗
PubMed1988

Role of thiols in the in-vitro methylation of inorganic arsenic by rat liver cytosol.

Rat liver cytosol inactivates inorganic arsenic (Asi) through methylation; S-adenosylmethionine is the methyl group donor and reduced glutathione (GSH) is required for full activity. The study of the combined effects of Asi, GSH and other thiols in vitro and the results of our previous in-vivo studies in humans and rats are consistent with a pathway involving the formation of a monomethylated metabolite which is either rapidly further methylated into a dimethylated derivative or is spontaneously oxidized into monomethylarsonic acid (MMA). The dimethylated metabolite gives rise to dimethylarsinic acid. The first methylation reaction is rate limiting, can be stimulated by GSH and is catalyzed by an enzyme different from that which transfers the second methyl group. The latter is sensitive to inhibition by inorganic arsenic. The stimulation of the first methylation reaction by GSH can only be evidenced at high Asi concentration because under these conditions, the second methylating enzyme can be sufficiently inhibited by Asi to allow some accumulation of MMA. The latter may also slow down the first methylation reaction. A large excess of thiol groups may prevent the methylation reactions probably by decreasing the amount of free trivalent arsenic.

Animals↗
PubMed1988

Plasminogen activator activity of cultured murine macrophages and effects of isopropylmethylphosphonofluoridate (sarin).

Casein-elicited mouse peritoneal macrophages cultured in the presence of phorbol 12-myristate 13-acetate (PMA) express u-PA. Induction is maximal after 4 hr of stimulation and u-PA activity is mainly recovered with the membrane fraction of the cellular lysate. This enzymatic activity is inhibited by isopropylmethylphosphonofluoridate after stimulation by PMA. The presence of the organophosphorus compound before stimulation does not affect the activity. The results of the present study on the kinetics of u-PA activity in cultured macrophages, its subcellular localization and the effect of an organophosphorus ester are consistent with the concept that the development of pericellular proteolysis proceeds through a series of stages, namely, (a) synthesis of pro-u-PA, (b) binding to membrane receptors, (c) activation to a double-chain u-PA, and (d) conversion of plasminogen into plasmin. The assay procedure developed here provides a sensitive tool to investigate the mechanism of interference of chemicals with several steps of induction of this enzymatic activity in macrophages.

Animals↗
PubMed1988

Latex immunoassay of serum alpha-fetoprotein using polyethylene glycol pretreatment.

A latex particle immunoassay has been developed for the determination of serum alpha-fetoprotein. The assay consists of incubating the serum sample for 30 min at 50 degrees C with latex particles coated with anti-alpha-fetoprotein immunoglobulin, then quantifying the remaining unagglutinated particles with an optical particle counter. The assay is fully automated with a sampling rate of 40/h. The interference from rheumatoid factor is eliminated by precipitation with polyethylene glycol (7% final concentration). The alpha-fetoprotein standard curve, prepared in a human serum matrix, extends from 0.5 to 32 micrograms/l. Because sera are diluted ten-fold, the limit of detection of the assay lies around 5 micrograms/l. Coefficients of variation ranged from 4 to 15% and the recovery of alpha-fetoprotein tested on eight normal sera and four sera containing rheumatoid factor averaged 102.2% (SD = 13.2). The correlation coefficient between latex immunoassay and radioimmunoassay, calculated from the assay of 138 samples was 0.98.

Humans↗
PubMed1988

Effect of renal insufficiency on the concentration of free retinol-binding protein in urine and serum.

The concentration of retinol-binding protein (RBP) in urine was determined in 20 healthy individuals and 119 patients with various renal diseases involving tubular or glomerular dysfunction. The sera from 4 healthy individuals and 33 patients were chromatographed on Sephadex G-75 to measure the concentration of free (i.e. not prealbumin-bound) RBP. In healthy individuals, the mean concentration of free RBP in serum was 5.8 mg/l and represented 14% of total RBP; the renal clearance and the fractional tubular uptake of free RBP averaged 0.032 ml/min and 99.97%, respectively. In patients, the concentration of free RBP and the percentage of free RBP in serum were on logarithmic scales inversely correlated with the endogenous creatinine clearance (r = -0.80 and -0.76) and increased in parallel with the serum creatinine (r = 0.67 and 0.66) and beta 2-microglobulin concentrations (beta 2-m, r = 0.76 and 0.89). The semi-logarithmic plot of urine versus serum concentration of free RBP suggests a renal threshold for the tubular reabsorption of this protein at a concentration of about 25 mg/l in serum. The existence of this threshold is confirmed by the relationship between urinary RBP and serum beta 2-m showing that urinary excretion of RBP is invariably high when the serum level of beta 2-m exceeds 5 mg/l. The latter value corresponds precisely to the renal threshold for the tubular reabsorption of beta 2-m. The corresponding value for free RBP derived from the relationship between both proteins is 24 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gel↗