Biomedical subjects

D Lison

Publications and source records attributed to D Lison.

At least 91 records · Page 5Linked to original sources

PubMed1994

Biological monitoring of workers exposed to cobalt metal, salt, oxides, and hard metal dust.

OBJECTIVE: The aim was to examine the relation between environmental and biological (blood and urine) indices of exposure to different chemical forms of cobalt. METHODS: A cross sectional study was undertaken in workers exposed to cobalt metal, oxides, and salts in a refinery and to a mixture of cobalt and tungsten carbide in a hard metal producing plant. RESULTS AND CONCLUSION: Although biological monitoring of workers exposed to cobalt oxides showed higher blood and urine concentrations than in non-exposed subjects, these indices poorly reflected the recent exposure level. By contrast, when exposure was to soluble cobalt compounds (metal, salts, and hard metals), the measurement of urine or blood cobalt at the end of the workweek could be recommended for the assessment of recent exposure. An eight hour exposure to 20 or 50 micrograms/m3 of a soluble form of cobalt would lead to an average concentration in a postshift urine sample collected at the end of the workweek of 18.2 or 32.4 micrograms of cobalt/g creatinine, respectively.

Adult↗

PubMed1994

Unusual manifestations after malathion poisoning.

We report a case of organophosphate poisoning with a commercial preparation of malathion (deliberate ingestion of Malathane Garden Spray: malathion 15% in isopropyl alcohol) in which the initial cholinergic crisis was followed by cardiac, pulmonary, neurological and renal manifestations. They occurred when erythrocyte and plasma cholinesterases were reactivating. A chemical analysis of the pesticide preparation revealed, apart from malathion itself, the presence of isopropylmalathion and O,O,S-trimethylphosphorothioate. Although pure malathion is regarded as one of the safest organophosphate insecticides, this observation underlines the possibility of severe complications after exposure to a preparation which has been stored for a long period of time.

Aged↗

PubMed1994

Acute and subacute organophosphate poisoning in the rat.

The intermediate syndrome in organophosphate poisoning is clinically characterized by weakness in the territory of cranial nerves, weakness of respiratory, neck and proximal limb muscles, and depressed deep tendon reflexes. It occurs between the acute cholinergic crisis and the usual onset of organophosphate-induced delayed neurotoxicity. The weakness has been ascribed to muscle fiber necrosis. Fenthion has been the most common cause. This study assesses the occurrence of the necrotizing myopathy in rats in relation to the clinical course and the acetylcholinesterase (AChE) inhibition after poisoning with organophosphates representative for each of the major types of organophosphate-related neurotoxicity. Marked differences are noted in the duration of cholinergic symptoms and of AChE inhibition after either paraoxon and mipafox, or fenthion poisoning. The necrotizing myopathy begins shortly after the initial decline in AChE activity with all organophosphates studied. Maximal muscle involvement occurs within the first 2 days of the poisoning with all organophosphates studied. The myopathy is not aggravated by a further decline in AChE activity in fenthion poisoning. Our data argues against the monophasic necrotizing myopathy being the cause of the intermediate syndrome, and is suggestive of persistent AChE inhibition being involved.

Animals↗

PubMed1993

Evaluation of the role of reactive oxygen species in the interactive toxicity of carbide-cobalt mixtures on macrophages in culture.

The lung toxicity of a carbide-cobalt mixture is more important than that of each individual component; the mechanism of this interaction is not understood. The capacity of cobalt metal particles alone and mixed with different carbides to generate hydroxyl radicals was examined with the deoxyribose assay. In a chemical system, cobalt ions and cobalt metal particles (Co) were found to catalyse the degradation of deoxyribose in the presence of hydrogen peroxide. Carbides were able to directly oxidize deoxyribose, but their respective activities did not support such a mechanism to explain the carbide-cobalt interactive toxicity, since there was no direct relationship between deoxyribose degradation ability and cytotoxicity toward macrophages. Tungsten, niobium, titanium and chromium carbides (interactive carbides) were only weak oxidants and conversely molybdenum, vanadium and silicon carbides (non-interactive carbides) were the most potent ones. The ability of cobalt metal to produce hydroxyl radicals in the presence of hydrogen peroxide was not increased by tungsten carbide. The role of reactive radical formation in the toxicity of these particles was further assessed in a macrophage culture model. Catalase (4000 U/ml), superoxide dismutase (300 U/ml), sodium azide (1 mM), sodium benzoate, mannitol, taurine and methionine (all 20 mM) were all unable to protect against the cytotoxic effects of cobalt ions and cobalt metal alone or mixed with tungsten carbide. In conclusion, no evidence was found that production of reactive oxygen species contributes to the elective toxicity of carbide-cobalt mixtures.

Animals↗

PubMed1993

Plasminogen activator activity and fertilizing ability of human spermatozoa.

Mature spermatozoa contain a number of proteases that are supposed to contribute to their fertilizing ability. The present study was directed at plasminogen activator (PA), a protease that belongs to the group of serine proteases and converts the zymogen plasminogen to the active broad-spectrum protease plasmin. To investigate the possible role of PA in the fertilization process, we have measured sperm-bound PA activity in 63 patients included in an in-vitro fertilization (IVF) programme and assessed their relationship to standard semen parameters and the rate of fertilization. PA activity was correlated significantly with the sperm count, as well as with sperm motility and morphology. Using logistic regression analysis, specific PA (pmol pNA 10(-6) cells min-2) was found to significantly influence the probability of fertilization. Other significantly predictive factors were motility and the percentage of spermatozoa with normal morphology. The sperm concentration (10(6) cells ml-1) did not significantly affect the outcome of IVF. We suggest that sperm-bound PA is involved in the fertilization process and may represent a potential indicator of sperm fertilizing capacity.

Female↗

PubMed1993

Epidemiological survey of workers exposed to cobalt oxides, cobalt salts, and cobalt metal.

Several organs (lung, skin, thyroid, heart, bone marrow) are potential targets of cobalt (Co). Whereas there is no doubt that inhalation of Co alone may cause bronchial asthma, its role in the occurrence of hard metal disease is still controversial because most cases were reported in workers exposed not only to Co but also to other substances such as tungsten carbide, titanium carbide, iron, silica and diamond. To assess whether exposure to pure Co dust (metal, oxides, or salts) may lead to adverse health effects a cross sectional study was carried out among 82 workers in a Co refinery. The results were compared with those in a sex and age matched control group. The Co group had been exposed for 8.0 years on average (range 0.3-39.4). The geometric mean time weighted average exposure assessed with personal samplers (n = 82) was about 125 micrograms/m3 and 25% of the values were higher than 500 micrograms/m3. The concentrations of Co in blood and in urine after the shift were significantly correlated with those in air. Concentration of Co in urine increased during the workweek. A slight interference with thyroid metabolism (decreased T3, T4, and increased TSH), a slight reduction of some erythropoietic variables (red blood cells, haemoglobin, packed cell volume) and increased white cell count were found in the exposed workers. The exposed workers complained more often of dyspnoea and wheezing and had significantly more skin lesions (eczema, erythema) than control workers. Within the exposed group a dose-effect relation was found between the reduction of the forced expiratory volume in one second/vital capacity and the intensity of current exposure to Co assessed by the measurement of Co in air or in urine. The prevalence of dyspnoea was related to the dustiness of the workplace as reflected by statistically significant logistic regression between this symptom and the current levels of Co in air and in urine. No difference between lung volumes, ventilatory performances, carbon monoxide diffusing capacity, and serum myocardial creatine kinase and procollagen III peptide was found between the Co and control groups and no lung abnormalities were detected on the chest radiographs in both groups. The results suggest that exposure to high airborne concentrations of Co alone is not sufficient to cause pulmonary fibrosis. This finding is compatible with experimental studies indicating that interaction of other airborne pollutants with Co particles play a part in the pathogenesis of parenchymal lung lesions.

Adult↗

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↗