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Biomedical subjects

D Lison

Publications and source records attributed to D Lison.

At least 91 records · Page 5Linked to original sources
PubMed1993

Biochemical changes associated with muscle fibre necrosis after experimental organophosphate poisoning.

1. This study was initiated to ascertain the possibility of biochemically monitoring the rhabdomyonecrosis that occurs after organophosphate poisoning. The evolution of different parameters has been assessed in the rat 6, 16, 24 and 48 h following 0.67 x LD50 of soman. 2. Acetylcholinesterase (AChE) was inhibited to 60% of the control value in the diaphragm at 6 and 16 h and serum ChE levels inhibited to an average of 30% of the control value. At 24 h, total blood, brain and diaphragm AChE were inhibited by 40, 69 and 38%, respectively. 3. Rhabdomyonecrosis lesions occurred in the diaphragm after 24 h and were accompanied by a concurrent increase in urinary creatine excretion rate (300% of the control) and serum total creatine phosphokinase activity (280% of the control). Calcium-activated neutral protease and phosphorylase a activities were elevated in the muscle at the same time. 4. These biochemical markers will prove useful for investigating the possible relationships between the different neuromuscular syndromes occurring in the course of an OP poisoning and potential therapeutic or protective pharmacological measures.

Acetylcholinesterase↗
PubMed1992

Comparative study of the acute lung toxicity of pure cobalt powder and cobalt-tungsten carbide mixture in rat.

Alveolitis progressing to lung fibrosis has been reported in workers exposed to cobalt containing dust (e.g., tungsten carbide-cobalt mixture as produced by the hard metal industry) but rarely following exposure to pure cobalt dust (e.g., in cobalt-producing factories). We have previously demonstrated that tungsten carbide-cobalt mixture is more toxic toward rat alveolar macrophages in vitro than pure cobalt metal powder. The present study was undertaken to compare in female rats the acute pulmonary response (lung weight, lung histology, cellular and biochemical analyses of bronchoalveolar lavage fluid, and mortality) following the intratracheal instillation of pure cobalt (Co) particles (median particle size, d50:4 microns), pure tungsten carbide (WC) particles (d50:2 microns), tungsten carbide-cobalt (WC-Co) powder (d50:2 microns; cobalt 6.3%, tungsten 84%, carbon 5.4%) and crystalline silica (d50 less than 5 micron) used as pneumotoxic reference material. WC alone (15.67 mg/100 g body wt) behaves as an inert dust producing only a mild accumulation of macrophages in the alveolar duct walls. Co alone (1.0 mg/100 g) only causes a moderate inflammatory response. An identical amount of Co given as WC-Co mixture (16.67 mg/100 g; corresponding to 1.0 mg Co/100 g) produces a severe alveolitis and fatal pulmonary edema. Cellular and biochemical characteristics of bronchoalveolar lavage fluid collected 24 hr after the intratracheal instillation of WC (1.0 mg/100 g) or Co (0.06 mg/100 g) are not significantly different from those of control animals instilled with sterile saline. On the contrary, bronchoalveolar lavage fluid changes following administration of the WC-Co mixture (1.0 mg/100 g; corresponding to 0.06 mg Co/100 g) are very similar to those induced by crystalline silica (1.0 mg/100 g). The amount of cobalt excreted in urine is significantly higher when the animals are exposed to WC-Co powder as compared to an equivalent amount of pure cobalt particles, suggesting an increased bioavailability of cobalt metal when combined with tungsten carbide. This study demonstrates that the acute lung toxicity of tungsten carbide-cobalt mixture is much higher than that of each individual component and may explain why lung fibrosis is rarely if ever induced by exposure to pure cobalt dust.

Animals↗
PubMed1992

Study of the mechanism responsible for the elective toxicity of tungsten carbide-cobalt powder toward macrophages.

We have previously demonstrated that tungsten carbide-cobalt powder (WC-Co) is more toxic toward murine macrophages in vitro than pure cobalt metal particles and that the cellular uptake of cobalt is enhanced when the metal is present in the form of WC-Co mixture. The present study was undertaken to assess the possible mechanism(s) of this interaction. We found that solubilization of cobalt in the extracellular milieu was increased in the presence of WC. This phenomenon, however, is not the critical factor explaining the greater toxicity of the WC-Co mixture since increasing the amount of solubilized cobalt in the extracellular medium in the absence of WC did not result in increased toxicity. Moreover, the amount of cobalt solubilized from a toxic dose of WC-Co was insufficient to affect by itself macrophage viability. A toxic effect was only observed when the WC-Co mixture came directly in contact with the cells. The elective toxicity of WC-Co can also not be explained by stimulation of phagocytosis of cobalt metal particles due to the simultaneous presence of other particles (WC) in the extracellular fluid since stimulation of phagocytosis by latex beads or zymosan particles did not amplify the toxicity of cobalt metal particles. These results indicate that the toxicity of the WC-Co mixture does not simply result from an enhanced bioavailability of its cobalt component. This suggests that hard metal dust behaves as a specific toxic entity.

Animals↗
PubMed1991

Induction of macrophage plasminogen activator by asbestos is independent of PKC activation.

This study was undertaken to assess whether plasminogen activator (PA) induction in macrophages exposed to chrysotile fibers is mediated by protein kinase C (PKC) activation. In PKC depleted J774 cells, PA induction could be elicited by chrysotile whereas, as expected, the response to phorbol myristate acetate (PMA) was abolished. The effect of PMA and chrysotile on the distribution of PKC activity in the J774 cell line was also compared by measuring the enzyme catalytic activity and phorbol dibutyrate (PDBu) binding sites. No redistribution of PKC was observed after stimulation with PA inducing doses of chrysotile, whereas a clear translocation was observed with PMA. It is concluded that the mechanism of PA induction by chrysotile in this macrophage-like cell line is independent of PKC activation.

Animals↗
PubMed1991

Effect of sulfur mustard on murine lymphocytes.

The effect on spleen cells of a single in vivo treatment with sulfur mustard was analyzed in mice 1 week after intoxication. A marked decrease in the number of total spleen cells was observed in mice receiving high doses of sulfur mustard. Flow cytometric analysis indicated that B-lymphocytes were relatively more affected than T-lymphocytes by this toxic compound. However, the function of remaining B-cells, measured by thymidine incorporation and immunoglobulin secretion in the presence of lipopolysaccharide, was not significantly impaired. In addition, sulfur mustard did not depress T-lymphocyte function since their proliferation in response to concanavalin A or to an anti-CD3 antibody was not affected by the treatment. These results suggest that whereas some observations reported in patients can be found in a murine model, additional in vitro studies with human lymphocytes could more adequately provide further information on sulfur-mustard-induced alterations of the immune system.

Animals↗
PubMed1991

Biological responses of isolated macrophages to cobalt metal and tungsten carbide-cobalt powders.

A previous study from this laboratory, using morphological and biochemical (LDH release) parameters, has shown that tungsten carbide-cobalt dust exhibits a greater cytotoxicity toward isolated macrophages than cobalt metal powder alone. The present study extends this comparison by examining additional biological parameters. Glucose uptake and superoxide anion production by isolated macrophages were significantly more depressed by the tungsten carbide-cobalt mixture (WC-Co) than by cobalt alone (Co) while pure tungsten carbide (WC) had no effect or even stimulated the cells. For glucose-6-phosphate dehydrogenase and cell-associated plasminogen activator (PA) activities, no difference between Co and WC-Co dusts was observed. These observations add further evidence to our previous findings regarding the different biological reactivity of cobalt metal alone or mixed with tungsten carbide.

Animals↗
PubMed1991

Importance of accurate employment histories of patients admitted to units of internal medicine.

A study was undertaken to assess the importance of systematically recording occupational histories of patients admitted to an internal medicine unit of a university hospital. Detailed information on current and past employment was obtained with questionnaires and in personal interviews from 200 inpatients over a 12-month period. Twenty-one patients (10.5%) were considered to have a "primary illness" (condition causing hospital admission) probably (4.5%) or possibly (6%) related to their current or previous occupation. From the 786 primary and secondary illness and medical antecedents diagnosed for the 200 patients examined, 70 illnesses of 55 patients were considered probably or possibly related to current or previous occupation. This pilot study emphasizes the need for accurate occupational records for patients in an internal medicine ward. This task is best performed by an appropriately trained occupational physician.

Adult↗
PubMed1991

Histological and histochemical study of paraoxon myopathy in the rat.

Time and dose dependency of paraoxon-induced myopathy in rats was studied in relation to esterase inhibition and clinical symptoms. High-dose poisoning resulted in a major cholinergic crisis with concomitant acetylcholinesterase inhibition in the first few hours with rapid restoration thereafter. Dose-dependent segmental muscle fiber necrosis occurred in clusters around the end-plates and was more frequent in diaphragms as compared to gastrocnemius muscles. However, in low-dose poisoned rats without major cholinergic symptoms or end-plate cholinesterase inhibition, necrotic fibers were also present. This indicates that not only end-plate cholinesterase inhibition but also neural or neuronal factors might be responsible for acetylcholine overflow and muscle fiber degeneration.

Animals↗
PubMed1990

Plasminogen activator activity of normal and retinoic acid-treated post-implantation embryos.

Urokinase-type plasminogen activator (uPA) has been implicated in cellular migration accompanying different biological phenomena including organogenesis. An increase in uPA activity was observed in mouse post-implantation embryos during the early organogenesis period. Since we have previously shown that all-trans retinoic acid (RA) prevented the induction of uPA in mouse peritoneal macrophages, we have now assessed whether teratogenic doses of this agent could also interfere with uPA activity in mouse embryo in vitro and in vivo. Post-implantation embryos (8.5 days) were incubated for up to 24 hr with micromolar concentration of RA resulting in the occurrence of malformations. No significant difference in uPA activity was found between control and treated embryos. Likewise, uPA activity was not altered in embryos explanted on day 9.5 from dams treated 24 hr before with a teratogenic dose of RA. This study indicates that the teratogenic activity of RA is not caused by an inhibition of the induction of uPA in embryos.

Abnormalities, Drug-Induced↗
PubMed1990

In vitro cytotoxic effects of cobalt-containing dusts on mouse peritoneal and rat alveolar macrophages.

"Hard metal disease" is a chronic lung disease characterized by the presence of interstitial fibrosis; the role of cobalt in the development of this entity is still debated. Indeed, most cases have been observed in some workplaces (grinding) of the hard metal industry and in the diamond polishing industry whereas no similar cases have been reported from workers exposed to pure cobalt powders in cobalt refineries. This study was designed to assess the in vitro toxicity (LDH release, morphology) of different cobalt-containing dusts toward murine peritoneal and alveolar macrophages. The results clearly demonstrate that, both in terms of dust particle and cobalt concentrations, the reactivity of the tungsten carbide-cobalt mixture is quite different from that of cobalt metal powder. The ground tungsten carbide-cobalt mixture prepared by the hard metal industry is almost as toxic as crystalline silica whereas, when tested separately, tungsten carbide has no effect and pure cobalt metal powder slightly impairs cell viability. The uptake of cobalt by macrophages in the presence of tungsten carbide was found to be increased. These observations may have some practical implications in industrial hygiene; they suggest that the acceptable exposure level to cobalt metal should be different when handled alone or in association with other powders such as tungsten carbide.

Animals↗
PubMed1990

Comparison of the effects of auranofin, heavy metals and retinoids on protein kinase C in vitro and on a protein kinase C mediated response in macrophages.

The effect of auranofin (AF), retinoic acid (RA), and three heavy metals reacting with thiol groups (Hg, Cd, Pb) has been compared on a PKC mediated response of intact macrophages (i.e. plasminogen activator (PA) induction) and on purified PKC activity. AF, cadmium chloride, and lead nitrate directly inhibit PKC and hence prevent the induction of PA activity in macrophages stimulated with PMA. In vitro, and in absence of chelators, mercuric chloride is also a potent inhibitor of PKC. However, at the cellular level, the PKC mediated response (PA induction) was not inhibited by non-cytotoxic concentrations of mercury possibly due to interference of the metal with additional cellular mechanisms such as calcium mobilisation. Direct inhibition of PKC is probably not the mechanism by which retinoids block the activation of macrophages.

Animals↗
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

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↗
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

In vitro effect of mercury and vanadium on superoxide anion production and plasminogen activator activity of mouse peritoneal macrophages.

The in vitro effects of mercuric chloride and vanadate were examined on two functions of mouse peritoneal macrophages, i.e., the superoxide anion production and the plasminogen activator (PA) activity. Vanadate, at concentrations which do not affect the viability of the cells, does not seriously alter any of these functions. High concentrations of mercury depress the respiratory burst; this effect results from loss of the reducing properties of cellular NADPH. Low concentrations of mercury stimulate the effect of phorbol 12-myristate 13-acetate on PA activity. The mechanism of this stimulation does not involve the protein kinase C system. It is hypothesized that mercury could enhance the synthesis of PA, its translocation to the cell surface, or its binding to the membrane receptors.

Animals↗
PubMedDate not supplied

Usefulness of biomarkers of exposure to inorganic mercury, lead, or cadmium in controlling occupational and environmental risks of nephrotoxicity.

A successful prevention of renal diseases induced by occupational or environmental exposure to toxic metals such as mercury (Hg), lead (Pb), or cadmium (Cd) largely relies on the capability to detect nephrotoxic effects at a stage when they are still reversible or at least not yet compromising renal function. The knowledge of dose-effect/response relations has been useful to control nephrotoxic effects of these metals through a "biological monitoring of exposure approach". Chronic occupational exposure to inorganic mercury (mainly mercury vapor) may result in renal alterations affecting both tubules and glomeruli. Most of the structural or functional renal changes become significant when urinary mercury (HgU) exceeds 50 micrograms Hg/g creatinine. However, a marked reduction of the urinary excretion of prostaglandin E2 was found at a HgU of 35 micrograms Hg/g creatinine. As renal changes evidenced in moderately exposed workers were not related to the duration of Hg exposure, it is believed that those changes are reversible and mainly the consequence of recently absorbed mercury. Thus, monitoring HgU is useful for controlling the nephrotoxic risk of overexposure to inorganic mercury; HgU should not exceed 50 micrograms Hg/g creatinine in order to prevent cytotoxic and functional renal effects. Several studies on Pb workers with blood lead concentrations (PbB) usually below 70 micrograms Pb/dl have disclosed either no renal effects or subclinical changes of marginal or unknown health significance. Changes in urinary excretion+ of eicosanoids was not associated with deleterious consequences on either the glomerular filtration rate (GFR)--estimated from the creatinine clearance (C(Cr))--or renal hemodynamics if the workers' PbB was kept below 70 micrograms Pb/dL. The health significance of a slight renal hyperfiltration state in Pb workers is yet unknown. In terms of Pb body burden, a mean tibia Pb concentration of about 60 micrograms Pb/g bone mineral (that is 5 to 10 times the average "normal" concentration corresponding to a cumulative PbB index of 900 micrograms Pb/dL x year) did not affect the GFR in male workers. This conclusion may not necessarily be extrapolated to the general population, as recent studies have disclosed inverse associations between PbB and GFR at low-level environmental Pb exposure. A 10-fold increase in PbB (e.g., from 4 to 40 micrograms Pb/dL) was associated with a reduction of 10-13 mL/min in the C(Cr) and the odds ratio of having impaired renal function (viz. C(Cr) < 5th percentile: 52 and 43 mL/min in men and women, respectively) was 3.8 (CI 1.4-10.4; p = 0.01). However, the causal implication of Pb in this association remains to be clarified. The Cd concentration in urine (CdU) has been proposed as an indirect biological indicator for Cd accumulation in the kidney. Several biomarkers for detecting nephrotoxic effects of Cd at different renal sites were studied in relation to CdU. In occupationally exposed males, the CdU thresholds for significant alterations of renal markers ranged, according to the marker, from 2.4 to 11.5 micrograms Cd/g creatinine. A threshold of 10 micrograms Cd/g creatinine (corresponding to 200 micrograms Cd/g renal cortex: the critical Cd concentration in the kidney) is confirmed for the occurrence of low-molecular-mass proteinuria (functional effect) and subsequent loss of renal filtration reserve capacity. In workers, microproteinuria was found reversible when reduction or cessation of exposure occurred timely when tubular damage was still mild (beta(2)-microglobulinuria < 1500 micrograms/g creatinine) and CdU had never exceeded 20 micrograms Cd/g creatinine. As the predictive significance of other renal changes (biochemical or cytotoxic) is still unknown, it seems prudent to recommend that occupational exposure to Cd should not allow that CdU exceeds 5 micrograms Cd/g creatinine.(ABSTRACT TRUNCATED)

Belgium↗
PubMedDate not supplied

Prospective study on the reversibility of neurobehavioral effects in workers exposed to manganese dioxide.

In 1987, a cross-sectional study in a dry-alkaline battery plant in Belgium revealed subclinical neurobehavioral dysfunctions associated with inhalation exposure to manganese dioxide (MnO2) particulate. The overall geometric mean of the time-weighted average concentration of manganese (Mn) in "total" dust (MnT) amounted, at that time, to 1 mg Mn/m3 and the duration of exposure was 5.5 years on average. An 8-year longitudinal investigation was conducted in this cohort (n = 92) in order to find out whether early effects on eye-hand coordination (EHC), hand steadiness (HST), and simple visual reaction time (VRT) were reversible when the airborne manganese concentration at the workplace was abated. During the observation period from 1988 to 1995, MnT monitoring was implemented on a monthly basis producing more than 1300 personal air samples, EHC tests were given yearly to assess the precision of the hand-forearm movement (PN1), and HST and VRT tests were carried out yearly since 1991. By the end of the study, the cohort size had dropped to 34 subjects. The model of unbalanced repeated measurements with unstructured covariance matrix and a time-varying covariate (log MnT) was the most appropriate to analyze the data. Wald chi 2 statistic was used for testing time-trends. The reduction of MnT over time was significantly associated with an improvement of the PN1 values (total cohort: Wald chi 2 = 8.5, p = 0.004; beta log MnT = -6.098 +/- 2.096). Like in the total cohort, time-trends were also found in the three exposure subgroups which could be identified in the cohort (average MnT over 1987-1992 were about 400, 600, and 2000 micrograms Mn/m3 for the low, medium, and high exposure subgroups, respectively). Only in the low exposure subgroup the PN1 value normalized when MnT (provisional estimates) decreased from about 400 to 130 micrograms Mn/m3 by the end of the study. Solely the reduction in MnT explained these findings on PN1, while a "healthy-worker-effect" mechanism was unlikely to have operated. The prognosis for the medium and high exposure subgroups remains uncertain as the improvement of their EHC performance may have been affected by past MnO2 exposure to such an extent that the persistence of a partial loss of EHC ability is suggested. The time courses of the HST and VRT test results, however, indicated the absence of any improvement, suggesting irreversible impairment of hand stability (postural tremor) and simple visual reaction time. A separate examination in a group of 39 control subjects, re-tested 10 years after the first test in 1987, virtually precluded age as confounding factor in this prospective study. The findings of the longitudinal study are corroborated by the outcome of a separate follow-up study in a group of 24 ex-Mn employees, who showed in 1996 a significant improvement of eye-hand coordination after at least three years with no MnO2 exposure; as to HST and VRT, there was no significant change in the deficit of these two neurobehavioral markers.

Adult↗