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Biomedical subjects

B Nemery

Publications and source records attributed to B Nemery.

At least 109 records · Page 6Linked to original sources
PubMed1992

The role of thiol oxidation in Cobalt(II)-induced toxicity in hamster lung.

Exposure of lung tissue to Co(II) ions both in vivo and in vitro results in toxicity, a relatively early event of which is the oxidation of cellular glutathione. In this study we have attempted to delineate the relationship between this oxidation of glutathione and the subsequent development of cellular dysfunction. Simultaneous incubation with H2O2 potentiated Co(II)-induced increases in both levels of oxidized glutathione (GSSG) and the activity of the pentose phosphate pathway in hamster lung slices. This effect was initially synergistic and, thereafter, both parameters were maintained at significantly greater levels than with either treatment alone throughout the incubation period until the onset of detectable cellular dysfunction. When dysfunction occurred, however, it was not quantitatively increased by the co-treatment over that occurring with CoCl2 alone. Similarly, pretreatment of slices with the glutathione reductase inhibitor 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) potentiated the Co(II)-induced increase in levels of GSSG. However, this effect was again not associated with an enhancement of cell dysfunction. Since the Co(II)-induced cell damage appeared not to be related directly to the oxidation of glutathione, the quantitative significance of the latter was investigated by comparison with the known oxidant tert-butyl hydroperoxide (t-BOOH). At a concentration of 100 microM, t-BOOH caused an increase in the concentration of GSSG in BCNU-pretreated lung slices which was comparable to that after treatment with Co(II)/H2O2 or CO(II)/BCNU. None of these treatments resulted in a loss of protein thiols. Furthermore, in contrast to Co(II), t-BOOH/BCNU treatment did not result in impaired cell functions. However, at a t-BOOH concentration of 250 microM, t-BOOH/BCNU treatment caused a significantly greater increase in the level of GSSG than that caused by the previous treatments and was associated with both a loss of protein thiols and increased cell dysfunction. We have concluded from these data that under our experimental conditions, Co(II)-induced cell dysfunction is not a consequence of oxidation of cellular glutathione. The reason for this appears to be that the extent of glutathione oxidation by Co(II) even at a concentration which induces cell dysfunction is not of sufficient magnitude to result in the oxidation of protein thiol groups, an event which is likely to constitute the critical consequence of glutathione oxidation in the toxic process.

Animals↗
PubMed1992

Lung injury induced by paraquat, hyperoxia and cobalt chloride: effects of ambroxol.

The effects of the surfactant stimulating drug ambroxol were studied in rats given paraquat (PQ, 15 mg/kg, s.c.), intratracheal cobalt chloride (CoCl2, 2.5 or 1.25 mg Co/kg) or exposed for 2 days to oxygen (greater than 95% O2). Ambroxol (50 mg/kg, i.p., twice daily) was given as a pretreatment for 4 days, or up to 7 days following pneumotoxic administration. Besides body weight evolution and lethality, various pulmonary indices were measured 2 days (O2) or 3 days (PQ and CoCl2) and 7 days after pneumotoxic treatment: wet and dry lung weight, total cell count, distribution of inflammatory cells and lactate dehydrogenase in bronchoalveolar lavage fluid, and histological damage assessed by a semiquantitative injury score. Neither form of ambroxol treatment prevented the toxicity of any of the pneumotoxic agents. The use of a combination of different indices of lung damage showed that different pneumotoxic agents may cause quite distinctive patterns of injury.

Ambroxol↗
PubMed1992

Survey of cobalt exposure and respiratory health in diamond polishers.

This cross-sectional study was undertaken after the discovery of cobalt-related fibrosing alveolitis and bronchial asthma in diamond polishers occupationally exposed to cobalt. A total of 194 workers from 10 diamond polishing workshops and 59 workers from three other workshops from the diamond industry (control subjects) were studied; a questionnaire was administered and spirometry was performed. Cobalt exposure was assessed by environmental air sampling using both area and personal sampling and by measuring urinary cobalt concentration. When considered on a workshop basis, these environmental and biologic indices of exposure correlated well with each other. These measurements led to the definition of three cobalt exposure categories: a no exposure group, a low exposure group, and a high exposure group. The high exposure was, however, still below the present threshold limit value for cobalt (50 micrograms/m3). Spirometry showed that indices of ventilatory function (FVC and FEV1) were significantly (p less than 0.05) lower in the group with the highest exposure to cobalt. These differences were not due to differences in smoking habits. The results were confirmed when the data were analyzed by covariance analysis of lung function indices against smoking status, taking mean cobalt exposure in each workshop as a covariate, and when the data were analyzed by multiple regression analysis. This analysis showed that cobalt exposure correlated with decreased pulmonary function. Our results suggest that, during diamond polishing, exposure to cobalt at levels below the current threshold limit value is associated, on a group basis, with measurable effects on lung function parameters. The relationship between these cross-sectional epidemiologic findings and the occurrence of overt lung disease in diamond polishers remains to be established.

Air Pollutants, Occupational↗
PubMed1991

Effects of injury on [3H]putrescine uptake by types I and II cells in rat lung slices.

The capacity of different lung parenchymal cells to accumulate putrescine was investigated by incubating slices of rat lung in a medium containing the tritiated compound. Quantitative examination of autoradiographs, by electron microscopy, indicated that accumulation of putrescine occurred in both the Type I and Type II cells of the alveolar epithelium. Putrescine uptake was abolished by the addition of spermidine to the medium or by incubating at 0 degrees C. Lung samples from rats dosed with the pneumotoxin O,S,S-trimethyl phosphorodithioate (OSSMeO), which selectively damages Type I pneumocytes, showed a large reduction in the uptake of label by both Type I and Type II cells. This treatment also resulted in an increase in the labeling of alveolar macrophages. Control samples, from undosed rats, were incubated in medium containing tritiated 5-hydroxytryptamine; this compound did not accumulate in epithelial cells but it was concentrated in the endothelium of the alveolar capillaries and in the blood cells within these vessels. The demonstration of putrescine uptake by both Type I and Type II pneumocytes, together with its reduction by dosing with OSSMeO, has vindicated the use of this activity, in lung slices, as an index of damage to the alveolar epithelium.

Animals↗
PubMed1991

Effects of pneumotoxic trialkylphosphorothioates on the pentose phosphate pathway in rat lung slices.

The extent of glucose oxidation via the pentose phosphate pathway (PPP), a possible indicator of oxidative stress, was assessed in rat lung slices by measuring the production of 14CO2 on incubation with either [6-14C]glucose or [1-14C]glucose. Incubation in the presence of the pneumotoxins O,S,S-trimethyl phosphorodithioate (OSSMe, 10(-5) -10(-3) M), O,O,S-triethyl phosphorothioate (10(-4) -10(-2) M) or S,S,S-trimethyl phosphorotrithioate (10(-4) -10(-2) M) resulted in a significant, but small stimulation of PPP (max. 276%), compared to that found in the presence of the model oxidant, paraquat (1089%, 10(-5) M). Following in vivo treatment with an LD50 dose of OSSMe, PPP was unchanged (after 6 h) or decreased (after 24 h) compared to saline-treated rats. PPP was also decreased in slices which had been preincubated with OSSMe (10(-3) M) and then transferred to fresh medium. Following treatment with phorone (250 mg/kg i.p.) pulmonary levels of non-protein sulfhydryls were first reduced (20% of control at 3 h) and then increased (288% of control at 24 h), but at neither time was lung slice PPP activity affected, thus suggesting that in the rat lung PPP activity does not directly depend on pulmonary glutathione content.

Animals↗
PubMed1991

Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies.

Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration-dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process.

Animals↗
PubMed1990

Bronchoalveolar lavage findings in a patient with the organic dust toxic syndrome.

A previously healthy student developed the organic dust toxic syndrome after unloading a grain silo for one day. Bronchoalveolar lavage seven days later showed a total cell count six times normal with 70% lymphocytes. This suggests that the previously described acute neutrophil influx into the alveolar spaces in this syndrome is rapidly replaced by a lymphocyte dominated infiltration.

Acute Disease↗
PubMed1990

Rapidly fatal progression of cobalt lung in a diamond polisher.

Interstitial lung disease was diagnosed in a 52-yr-old male diamond polisher, who worked with polishing disks containing cobalt. After a further 7 months of probably high occupational exposure without any specific treatment, he had to quit work because of dyspnea. Despite treatment with systemic corticosteroids and continuous oxygen administration, he died 3 months later in respiratory distress. Postmortem examination of the lung tissue showed a typical giant-cell interstitial fibrosis, with active inflammatory cell infiltration superimposed on an established centrilobular fibrosis. The lung tissue contained 2.1 micrograms cobalt/g wet weight (more than 100-fold the normal concentration); cobalt particles, mainly localized in macrophages, were identified by transmission electron microscopy and energy-dispersive X-ray analysis. We speculate that the rapid deterioration and fatal outcome resulted from the continued exposure to cobalt, leading to a high pulmonary concentration of cobalt, and from the oxygen treatment because cobalt promotes the formation of hydroxyl free radicals.

Air Pollutants, Occupational↗
PubMed1990

Metal toxicity and the respiratory tract.

The type of lung disease caused by metal compounds depends on the nature of the offending agent, its physicochemical form, the dose, exposure conditions and host factors. The fumes or gaseous forms of several metals, e.g. cadmium (Cd), manganese (Mn), mercury (Hg), nickel carbonyl (Nl(CO)4, zinc chloride (ZnCl2), vanadium pentoxide (V2O5), may lead to acute chemical pneumonitis and pulmonary oedema or to acute tracheobronchitis. Metal fume fever, which may follow the inhalation of metal fumes e.g. zinc (Zn), copper (Cu) and many others, is a poorly understood influenza-like reaction, accompanied by an acute self-limiting neutrophil alveolitis. Chronic obstructive lung disease may result from occupational exposure to mineral dusts, including probably some metallic dusts, or from jobs involving the working of metal compounds, such as welding. Exposure to cadmium may lead to emphysema. Bronchial asthma may be caused by complex platinum salts, nickel, chromium or cobalt, presumably on the basis of allergic sensitization. The cause of asthma in aluminium workers is unknown. It is remarkable that asthma induced by nickel (Ni) or chromium (Cr) is apparently infrequent, considering their potency and frequent involvement as dermal sensitizers. Metallic dusts deposited in the lung may give rise to pulmonary fibrosis and functional impairment, depending on the fibrogenic potential of the agent and on poorly understood host factors. Inhalation of iron compounds causes siderosis, a pneumoconiosis with little or no fibrosis. Hard metal lung disease is a fibrosis characterized by desquamative and giant cell interstitial pneumonitis and is probably caused by cobalt, since a similar disease has been observed in workers exposed to cobalt in the absence of tungsten carbide. Chronic beryllium disease is a fibrosis with sarcoid-like epitheloid granulomas and is presumably due to a cell-mediated immune response to beryllium. Such a mechanism may be responsible for the pulmonary fibrosis occasionally found in subjects exposed to other metals e.g. aluminium (Al), titanium (Ti), rare earths. The proportion of lung cancer attributable to occupation is around 15%, with exposure to metals being frequently incriminated. Underground mining of e.g. uranium or iron is associated with a high incidence of lung cancer, as a result of exposure to radon. At least some forms of arsenic, chromium and nickel are well established lung carcinogens in humans. There is also evidence for increased lung cancer mortality in cadmium workers and in iron or steel workers.

Asthma↗
PubMed1988

Studies on the metabolism of the pneumotoxin O,S,S-trimethyl phosphorodithioate--I. Lung and liver microsomes.

The metabolism of O,S,S-trimethyl phosphorodithioate (OSSMe), a pneumotoxic impurity in some organophosphorus insecticides, was investigated in rat lung and liver microsomal preparations, using OSSMe labelled with 3H or 14C on one of its thiolo-methyl (CH3S-) groups. Production of O,S-dimethyl phosphorothioate (OSMeO-) and binding of radioactivity to protein were NADPH-dependent and were shown to be, at least partly, cytochrome P-450-dependent processes in both lung and liver microsomes. Incubation with reduced glutathione prevented the binding of radioactivity without affecting OSMeO- production. The Km for the conversion of OSSMe to OSMeO- was 15-fold lower in lung (0.30 +/- 0.07 mM) than in liver (4.63 +/- 2.42 mM) microsomes. These results show that cytochrome P-450-dependent mixed-function oxidase is implicated in at least part of the metabolic activation of OSSMe, and suggest that the pulmonary isozyme(s) are more active at metabolizing OSSMe than hepatic isozymes. It is speculated, on the basis of literature data on other sulphur-containing chemicals, that the metabolic activation of OSSMe involves oxidation of a thiolo-sulphur, with subsequent formation of CH3-S-S-protein disulphides.

Animals↗
PubMed1988

Studies on the metabolism of the pneumotoxin O,S,S-trimethyl phosphorodithioate--II. Lung and liver slices.

The metabolism of O,S,S-trimethyl phosphorodithioate (OSSMe), a pneumotoxic impurity in some organophosphorus insecticides, was investigated by incubating rat lung and liver slices with 1 mM OSSMe, labelled with 3H or 14C on one of its thiolo-methyl (CH3S-) groups. Protein bound radioactivity was higher in lung slices than in liver slices. In lung slices the predominant diester produced was O,S-dimethyl phosphorothioate (OSMeO-), whereas in liver slices it was S,S-dimethyl phosphorodithioate (SSMeO-). Other studies had shown binding of radioactivity and OSMeO- production to be cytochrome P-450-dependent processes in microsomes and SSMeO- production to result from the action of cytosolic glutathione-S-transferase on OSSMe. Preincubation of slices with 10(-5) M paraoxon did not influence the amount of protein-bound radioactivity, suggesting that binding of radioactivity did not simply result from protein phosphorylation. Pretreatments of the rats with O,O,O-trimethyl phosphorothioate [OOOMe(S) 0.5, 2.5 and 12.5 mg/kg p.o.], with p-xylene (1 g/kg, i.p.) or with bromophos (5.3 mg/kg, i.p.) which all protect against the lung toxicity of OSSMe probably by inhibiting pulmonary mixed-function oxidase, also led to significant decreases in both protein binding of radioactivity and OSMeO- production in lung slices, but not in liver slices. These results show that tissue slices are a convenient system for investigating xenobiotic metabolism in the lung and they suggest that the susceptibility of the lung to OSSMe probably results from a relatively high rate of activation, coupled with a relatively low rate of metabolism by non-toxic pathways and/or removal of reactive metabolites in some lung cells, possibly the alveolar type I cells.

Animals↗
PubMed1988

Byssinosis in a textile factory in Cameroon: a preliminary study.

To assess the risk of byssinosis in a cotton textile factory in Cameroon a preliminary study was conducted on a random sample of 125 men from production areas and 68 men from non-production areas. Symptoms were assessed by a questionnaire, which also included questions regarding sleep; peak expiratory flow rate (PEF) was measured with a miniature peak flow meter at the end of a working day and total dust concentrations were assessed by static and personal sampling with Casella dust samplers giving values of 6.4 +/- 2.6 mg/m3 (m +/- SD) in production areas and 1.7 +/- 0.7 mg/m3 in control areas. Exposed subjects had significantly more symptoms (particularly in smokers) and lower PEF values than controls (408 +/- 961/min v 468 +/- 701/min, p less than 0.001). Twenty three exposed subjects (18%) reported chest tightness on returning to work after the weekly break (compared with one control, p less than 0.01). Subjects with byssinosis had lower PEF values than those without chest tightness (356 +/- 501/min v 426 +/- 951/min, p less than 0.01), more chronic bronchitis (52% v 6%, p less than 0.001), they were more often smokers (61% v 31%, p less than 0.05), and came generally, though not exclusively, from the opening carding spinning department with the highest concentrations of total dust (8 +/- 2 mg/m3) and an estimated prevalence of byssinosis of 28%. There were no significant differences in sleep related symptoms between the exposed and controls, though the 23 subjects with byssinosis tended to report more snoring (48%), early morning headache (48%), and sleep improvement over the working week (44%) than all the other subjects (28%, 24%, and 24% respectively, p less than 0.1).

Adult↗
PubMed1987

Impairment of ventilatory function and pulmonary gas exchange in non-smoking coalminers.

Indices of ventilatory function and pulmonary gas exchange in 32 non-smoking coalminers (mean age 38.1) were compared with those of 34 non-smoking steelworkers of similar age. The coalminers had significantly lower forced expiratory volume in 1 s (FEV1) and maximum expiratory flow rates and significantly higher residual volume, but similar vital capacity and indices derived from the single-breath test. Pulmonary diffusing capacity for CO and indices of CO2 exchange were similar in both groups. Arterial partial pressure of O2 (PaO2) was significantly lower and alveolar-arterial O2 difference was significantly higher in coalminers than in controls, both at rest and during exercise. There was no relation between lung function and radiological signs of simple pneumoconiosis (10 coalminers had pneumoconiosis). The differences in FEV1 (0.42 l) and in PaO2 (10 mm Hg) between the two groups are the same or larger than those usually found between smokers and non-smokers. Exposure to coaldust may result in biologically significant alterations of lung function even in the absence of pneumoconiosis.

Adult↗
PubMed1987

Respiratory and non-respiratory lung function indices during the development and resolution of O,S,S-trimethyl phosphorodithioate-induced lung damage in the rat. A chemical model of adult respiratory distress syndrome.

Arterial blood gases and the pulmonary uptake of putrescine and 5-hydroxytryptamine (5-HT) were studied between 6 h and 18 days after the administration to rats of an oral LD50-dose of the pneumotoxin, O,S,S-trimethyl phophorodithioate (OSSMe), a potential impurity in several organophosphorus insecticides. Aortic blood was sampled under pentobarbitone anaesthesia for measurements of arterial pH, and partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). PaO2 was significantly decreased 4 days after OSSMe administration, i.e. at the time of maximum lethality and increases in wet lung weight. This was accompanied by a significant increase in PaCO2 and acidosis. These results are compatible with an impairment of gas exchange due to diffuse lung damage. For reasons that are unclear, PaCO2 was slightly increased 2, 6 and 12 days after dosing. The uptake of putrescine (1,4-diaminobutane) and of 5-HT was measured by incubating lung slices with several concentrations of [3H]-putrescine and [14C]-5-HT, so as to estimate the apparent kinetic parameters of uptake, Vmax and Km. The Vmax for putrescine-uptake was significantly decreased 1, 2, 4, 6 and 12 days after the administration of OSSMe. The Vmax for 5-HT-uptake was significantly increased 1 day and significantly decreased 4 days after OSSMe administration. The uptake of 5-HT is an endothelial function, and the decrease in 5-HT-uptake at 4 days may reflect injury to the pulmonary vascular endothelium at this time. The uptake of putrescine probably reflects the function of the pulmonary (mainly alveolar) epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Ultrastructural changes in the respiratory tract of rats following methyl isocyanate inhalation.

The static exposure of rats to 0.25 mg/l methyl isocyanate for 1 h resulted in damage to the epithelium of the proximal bronchioles and upper airways. Bronchiolar cells exhibited both nuclear and cytoplasmic damage; many epithelial cells, particularly in the bronchi and trachea, were killed and/or dislodged from the basement membrane. A "raft" of cell debris and fibrin lined most of the airways during the 1st week after exposure but repair to the underlying epithelium was well advanced within 2-3 days. The majority of airways were lined by a normal epithelium within 3 weeks of exposure, but isolated foci of hyperplasia and occluded airways probably accounted for continued respiratory impairment.

Animals↗