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Biomedical subjects

R Bégin

Publications and source records attributed to R Bégin.

At least 55 records · Page 3Linked to original sources
PubMed1992

Pulmonary clearance of fibrous and angular SiC particulates in the sheep model of pneumoconiosis.

Both angular and fibrous SiC (carborundum) particulates can be emitted by SiC production operations. Carborundum pneumoconiosis is now recognized as an occupational lung disease with specific pathological features. These were previously reproduced in the sheep model of pneumoconiosis with fibrous SiC but not with angular SiC. To further document this question, the pulmonary retention in the sheep of the two morphological types was studied. Animals were injected in the tracheal lobe with equal mass (100 mg) of particulates prepared from SiC materials taken in the field. Particles were measured by analytical transmission electron microscopy in samples of bronchoalveolar lavage fluids (BAL) obtained at months 2, 4, 6 and 8 after the injection. They were also measured in samples of lung parenchyma obtained at month 8. Measurements in BAL and in lung samples both indicated a much lower retention for fibrous than for angular SiC. The retention rate in lung parenchyma at month 8 was 30 times lower for fibrous SiC. The half-life of decrease of concentrations was 3.4 times shorter for fibrous SiC. Other data in the literature support the notion that fine fibres are cleared more effectively than coarser angular particles.

Animals↗
PubMed1991

Silicon carbide pneumoconiosis: a radiographic assessment.

Interstitial lung disease and airflow limitation have been reported in silicon carbide workers but it is uncertain whether these recent observations reflect past working conditions alone (30 years ago) or both past and present conditions even if the latter have improved. To investigate this, we analyzed pairs of chest radiographs obtained in 1977 and 1984 in 128 silicon carbide plant workers. Three indices, related to density of small opacities, profusion of opacities, and presence of pleural plaques, were obtained. Student t-tests on results obtained in each time period showed the mean density (1.02 in 1977 and 0.56 in 1984) and profusion (4.27 in 1977 and 2.13 in 1984) indices to be significantly different. However, the pleural plaque index was not different in 1984 (0.34) as compared with 1977 (0.32). There was no deterioration of the radiographic image even in groups with density ratios equal or greater than 1/1. We concluded that the actual environmental working conditions did not influence the integrity of the lung radiographic image in these workers within a time span of 6 or 7 years.

Adolescent↗
PubMed1991

Glutathione and inflammatory disorders of the lung.

Glutathione (GSH) is an essential tripeptide present in most eukaryotic cells. Because of its sulfhydryl group, GSH is a versatile molecule capable of protecting cells against oxidants and toxic xenobiotics. However, it also plays key roles in multiple metabolic pathways, such as the synthesis of certain leukotrienes, proteins, and DNA precursors as well as the activation of enzymes, the regulation of immune responses and others. Not only is GSH synthesized by cells for local use but it also participates in an elaborate intercellular exchange process regulated by the gamma-glutamyl cycle. Extracellular GSH in plasma and in alveolar epithelial lining fluid is thus subject to variations according to the degree of expression of gamma-glutamyl cycle enzymes and the rate of consumption of GSH by electrophilic molecules. Bronchoalveolar lavage has allowed us to observe many of these variations of GSH within the extracellular environment of the normal and diseased human lung. Studies of lung GSH have lead to a better understanding of pathogenic processes and have stimulated investigations of novel therapeutic approaches in lung inflammatory disorders.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Computed tomography scan in the early detection of silicosis.

We evaluated the ability of both the conventional and high resolution computed tomography (CCT and HRCT, respectively) scans of the thorax to detect early silicosis in subjects exposed to silica dust in the mines and foundries of Québec for an average of 29 +/- 2 yr. The study was limited to subjects with chest radiograph (CR) of the International Labor Organization (ILO) Categories 0 or 1 as determined independently a priori. All subjects had a standard high-kilovoltage posteroanterior and lateral CR, a set of 10 to 15 1 cm collimation CCT scans, and a set of three to five 2 mm collimation HRCT scans in the upper, middle, and lower lung fields. For each CR and sets of CT scans, readings were done independently by four experienced readers. For small opacities of the lung parenchyma on CR, 32 of the 51 subjects were normal (Group A), six were indeterminate (Group B), and 13 were abnormal (Group C). By the combined readings of HRCT and CCT, 13 of the subjects (40%) in Group A were abnormal (p less than 0.001); four of the subjects in Group B were abnormal, and in Group C, one subject was normal, one indeterminate, and 11 (84%) abnormal. For confluence of small opacities, 48 of the 51 subjects were negative (Group 0), and three were positive (Group 1) on the CR. By the CT scan, 42 of the 48 subjects in Group 0 were negative, and the three subjects in Group 1 were positive; thus the CT scan added six positive cases with confluence of small opacities (six of 48, 12.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Enzyme activities of lung lavage in silicosis.

The cytotoxic effect of quartz on lung cells has been well documented by in vitro and animal studies, but the pertinence of these findings to humans has not yet been documented. We measured lactate dehydrogenase (LDH) activities in the lung lavage of 24 long-term workers in the Québec granite industry and 25 control subjects. We found significant increases in LDH activities in the workers' lung lavage, even in the absence of established silicosis (9 subjects). We looked at a similar observation in the sheep model of early silicosis, measured quartz content of lung lavage, and found significant correlation with LDH levels (R = 0.64, p less than 0.001). All of the quartz particles in human and sheep lung lavage were in the alveolar macrophages. To test further the relationship of macrophage damage (cytotoxicity of quartz) we measured the release of LDH by sheep alveolar macrophage in 24 h cell culture under control conditions, exposure to inert dust, titanium, minusil-5 quartz, or aluminum-treated quartz. The LDH release was at control levels during titanium exposure and showed a significantly dose-related increase during quartz exposure. The latter cytotoxic effect was largely attenuated by aluminum treatment of quartz. These in vitro data agreed with previous reports. This study presents evidence of a cytotoxic effect of quartz inhalation in humans. The effect is related to the intensity of quartz retention in the lung macrophages; it is not a nonspecific dust exposure effect and can be attenuated by surface modification of the quartz.

Adult↗
PubMed1990

Mass, number and size of lung fibres in the pathogenesis of asbestosis in sheep.

After long-term asbestos inhalation, the lung tissue burden is much less for chrysotile (CHRY) than for crocidolite (CRO) exposure. Nonetheless CHRY does not appear to be less fibrogenic. To study mechanisms responsible for the low retention of CHRY and the relationships with fibrogenesis, 15 sheep received a single intratracheal injection of either CHRY or CRO. Exposures in 100 ml saline consisted of 100 mg of 1-micron latex beads for the five control sheep, 100 mg UICC CRO fibres for the five CRO sheep and 100 mg UICC B CHRY fibres for the five CHRY sheep. Bronchoalveolar lavage (BAL) was carried out at months 2, 4, 6 and 8 after exposure and necropsy at month 8. BAL and tissue samples were analysed for fibres by transmission electron microscopy. At month 2, mass concentration in BAL was 108 +/- 30 ng/ml for CRO and 0.6 +/- 0.1 ng/ml for CHRY. BAL CRO decreased afterward but BAL CHRY did not. The mass concentration in the lung at month 8 was 40.6 +/- 8.7 ng/mg dry tissue for CRO and 11.5 +/- 7.0 ng/mg for CHRY. BAL fibrogenic activity at month 8 assessed by macrophage fibronectin production was less than 0.2 ng/10(6) cells/24 h in control sheep, 5 +/- 2 in CRO sheep and 11 +/- 2 in CHRY sheep (P less than 0.05 CRO vs CHRY). Histologic score of tissue injury fibrosis was 0 in control sheep, 1.9 +/- 0.3 in CRO sheep and 2.8 +/- 0.1 in CHRY sheep (P less than 0.05). At necropsy, the number size distribution of fibres per microgram of tissue from the (CRO)/(CHRY) sheep was respectively: (127 +/- 54)/(15 +/- 14) for fibres less than 5 microns, (18 +/- 17)/(32 +/- 14) for fibres greater than 5 microns, (1.6 +/- 8)/(7 +/- 13) for fibres greater than 20 microns. This study documented that the low pulmonary retention of CHRY was largely related to the faster alveolar clearance rate of CHRY mass. Fibrogenicity of CHRY remained higher and appeared to be related at least in part to the preferential retention of long and very long CHRY fibres.

Animals↗
PubMed1990

Chrysotile asbestos exposures can produce an alveolitis with limited fibrosing activity in a subset of high fibre retainer sheep.

Inhalation of fibrogenic mineral dust may enhance fibronectin (Fn) production by alveolar macrophages and increase fibroblast growth activity (FGA) in lung lavage fluid. To investigate the relationship of these changes to fibre retention and the development of asbestosis, we exposed 15 sheep to 100 mg Canadian chrysotile fibres in 100 ml saline, and ten sheep to 100 ml saline only, at ten day intervals. The animals were studied at 3 month intervals. At month 18, ten sheep had abnormal chest radiograph (category greater than or equal to 1) (group B) and five had normal radiograph (category 0) (group A). Pulmonary function data indicated restrictive patterns of abnormalities in both groups, more severe in group B. Sheep in group A had bronchoalveolar lavage (BAL) cellularity and biochemistry comparable to controls; sheep in group B had significant increases in total BAL cells (x2), macrophages (x2), neutrophils (x4) and eosinophils (x3), increased BAL lactate dehydrogenase and Fn, but FGA and procollagen 3 comparable to controls. Fibre retention was significantly increased in all exposed sheep and 2.5 x higher in group B vs group A despite similar exposures (70 intratracheal, 100 mg chrysotile infusions). Enhanced fibre retention in group B preceded the appearance of disease. This study confirms our earlier observation linking individual susceptibility to development of alveolitis to individual dust burden and provides evidence that the excess of fibre retention can be observed before detectable disease. In addition, we report a chrysotile-induced early alveolitis with incompletely expressed fibrosing activity at the time of initial radiographic detection. The intensity of the alveolitis is related to the degree of fibre retention.

Animals↗
PubMed1989

Granulocyte elastase-mediated proteolysis of alpha 1-antitrypsin in cystic fibrosis bronchopulmonary secretions.

Airway secretions of patients with cystic fibrosis (CF) contain large amounts of alpha 1-antitrypsin (alpha 1-AT), yet elastase activity is also often detectable, suggesting that airway alpha 1-AT may not be functional in some CF patients. It is unknown whether in CF sputum alpha 1-AT is inactivated by oxidants, neutrophil metalloproteinases, bacterial elastase, or neutrophil elastase. To investigate the mechanism(s) by which alpha 1-AT may be inactivated in CF airway secretions, sputum samples were obtained from nine patients during respiratory physiotherapy. alpha 1-AT was measured by radial immunodiffusion. Sputum-alpha 1-AT was purified by antibody affinity chromatography. Electrophoresis of alpha 1-AT from seven patients with acute infectious exacerbations revealed two distinct components: a minor band corresponding to an elastase/alpha 1-AT complex and a major band typical of proteolysed alpha 1-AT (Mr = 48 kD). Each patient had large amounts of sputum elastase activity. In contrast, two patients without free sputum elastase activity had intact sputum alpha 1-AT; however, alpha 1-AT was partially truncated by porcine pancreatic elastase suggesting that the alpha 1-AT may have been partially oxidized. Adding alpha 1-AT purified from normal serum to alpha 1-AT-depleted sputum containing elastase activity resulted in a small alpha 1-AT/elastase complex with most alpha 1-AT being truncated. The serine proteinase inhibitor phenylmethylsulfonyl fluoride but not the metalloproteinase inhibitor EDTA prevented alpha 1-AT proteolysis, thus granulocyte elastase can mediate alpha 1-AT degradation in CF. Apparently, the large granulocyte elastase burden in some acutely ill patients with cystic fibrosis can proteolytically inactivate alpha 1-AT.

Adolescent↗
PubMed1989

Effect of aluminum inhalation on alveolar phospholipid profiles in experimental silicosis.

In the sheep tracheal lobe model of silicosis, we have recently reported that total phospholipid, lecithin, and phosphatidylglycerol levels were elevated in lung lavage. To investigate further this observation, we obtained complete phospholipid profiles of lung lavage in 10 sheep exposed to saline only (Sa group), 10 sheep exposed to aluminum lactate inhalation only (Al group), 10 sheep exposed to 100 mg Minusil-5 in saline followed by monthly saline inhalation (Si group), and 10 sheep exposed to 100 mg Minusil-5 in saline followed by monthly aluminum lactate inhalation (Si-Al group). The following phospholipid components were measured: total phospholipids, phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine, disaturated phosphatidylcholine, sphingomyelin, and lyso-phosphatidylcholine. All values were comparable in the Sa group, Al group, and Si-Al group. In the Si group, there was a significant increase in total phospholipid to approximately 200% of the control values. The phospholipid profile of this group demonstrated an increase in all of the phospholipid components with some enrichment of the fraction of PG, PE, and PI. We concluded that lung exposure to silica dust significantly increases the concentration of phospholipids in the alveoli. This increase is of a large spectrum of alveolar phospholipids and is completely suppressed by aluminum lactate inhalation.

Administration, Inhalation↗
PubMed1989

Increased alveolar plasminogen activator in early asbestosis.

Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Carborundum pneumoconiosis. Fibers in the mineral activate macrophages to produce fibroblast growth factors and sustain the chronic inflammatory disease.

Carborundum is a synthetic abrasive manufactured through fusion of high grade silica sand and finely ground carbon in an electric furnace at 2,400 degrees C. It had been considered an inert dust until recently. Two recent epidemiologic studies in Quebec have documented an excess of interstitial lung disease in plant workers and some 30 workers have received workman compensation. Histopathologic lesions have been described in four of the workers. To further investigate the carborundum pneumoconiosis, nine groups of eight sheep were exposed once in the tracheal lobe to either 100 ml saline, 100 mg latex beads in 100 ml saline, 100 mg graphite in 100 ml saline, 100 mg carborundum particles in 100 ml saline, 100 mg ashed carborundum particles in 100 ml saline, 100 mg of quartz (Minusil-5) in 100 ml saline, 100 mg crocidolite fibers in 100 ml saline, 100 mg carborundum fibers in 100 ml saline, and 100 mg ashed carborundum fibers in 100 ml saline solutions. The animals had BAL at two-month intervals and autopsy at month 8. The BAL analyses of cellularity, cytotoxicity and fibrogenicity, in association to necropsy histopathology, documented that all particles except for quartz were inert. The two-carborundum fiber samples produced a similar sustained nodular fibrosing alveolitis and crocidolite asbestos fibers produced a peribronchiolar fibrosing alveolitis of comparable severity. Thus, the major bioactive dusts in the carborundum manufacturing process are quartz particles and the carborundum fibers generated in the process. The latter have fibrogenic activities comparable to asbestos fibers of similar size and are likely to contribute to the pathogenesis of the interstitial lung disease of carborundum workers.

Animals↗
PubMed1989

Quartz exposure, retention, and early silicosis in sheep.

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.

Animals↗
PubMed1989

Excessive accumulation of asbestos fibre in the bronchoalveolar space may be a marker of individual susceptibility to developing asbestosis: experimental evidence.

Earlier studies have shown that only 60% of sheep exposed to a given chrysotile exposure developed asbestosis. Analyses of lung lavage (BAL) fibre content early in the disease showed that, despite identical injected doses, the subset of sheep with interstitial lung disease had significantly more fibre retention. To determine if the fibre retention preceded or followed early disease, 15 were exposed at 10 day intervals to 100 mg chrysotile by intratracheal injection. Animals were studied at three month intervals by chest radiograph (CR) and BAL. At month 15, 10 sheep had definitely abnormal CR (group B) and five had normal CR (group A). Fibre analyses of BAL reproduced earlier finding of a higher level of fibre retention early in the disease, month 15: 92 +/- 2 f/microliter in group B v 35 +/- 19 in group A. Moreover, at month 3, when no disease was detectable, group B already had a significantly higher fibre retention level: 84 +/- 2 in group B v 52 +/- 3 in group A (p less than 0.05). These data clearly imply that high alveolar dust retention precedes the disease process and that alveolar dust clearance capacity may be a major determinant of asbestosis.

Animals↗
PubMed1989

Recent advances in the pathogenesis and clinical assessment of mineral dust pneumoconioses: asbestosis, silicosis and coal pneumoconiosis.

Recent investigations of the fundamental mechanisms of the mineral dust diseases have substantially increased our understanding of the pathogenesis of the pneumoconioses. In all the mineral dust pneumoconioses, the initial early lung lesion is a fibrosing macrophagic alveolitis. The additional contribution of other lung cell populations is currently under investigation and may identify specific processes for each of the pneumoconioses. Clinical investigations have also progressed with new tools such as Gallium-67 lung scanning, bronchoalveolar lavage analyses, and CT scanning of the thorax; their established values are reviewed in this paper, and areas where progress is needed are considered. The clinical progress in the mineral dust diseases is clearly linked to the basic understanding of the mechanisms of these diseases.

Asbestosis↗
PubMed1988

Lung exposure to mineral dusts enhances the capacity of lung inflammatory cells to release superoxide.

In vitro exposure of macrophages and neutrophils to inorganic dusts can enhance their oxidative metabolism, however the effects of inorganic dust inhalation on lung-inflammatory cell-oxidative metabolism remain unknown. To address this issue, we studied the superoxide anion release from lung inflammatory cells obtained by bronchoalveolar lavage from 19 sheep exposed repeatedly to UICC chrysotile B asbestos (100 mg) over an 18 month period and 10 sheep exposed to a single exposure of quartz (100 mg) over a 6 month period. Exposure to asbestos and quartz did not induce an increase in the spontaneous release of superoxide from inflammatory cells. However lung-inflammatory cells from sheep exposed to asbestos released much higher levels of superoxide in the presence of phorbol myristate acetate (PMA) than did cells of unexposed sheep. In quartz exposed animals, superoxide release with PMA stimulation remained significantly increased up to 2 months after a single quartz infusion. These results suggest that inorganic dust inhalation primes lung inflammatory cells in vivo and markedly enhances their capacity to release toxic oxygen radicals.

Animals↗