Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study, consisted of two separate surveys, was initiated to clarify the development of clinical pictures of silicosis after termination of dust exposure. The first survey was a 40-year follow-up of radiographic pictures of the chest among 200 male whetstone cutters (Group I workers). The second survey was conducted in 75 male recipients (Group II workers) of disability compensation for silicosis due to whetstone dust exposure. The study on Group I workers made it clear that the proportion of those free of radiographic findings in the chest pictures decreased during a 40-year follow-up period from 84% in the 1st health examination in 1952-6 to 36% in the 3rd examination in 1995. The rate of progression of the disease from Category 1 to 3 (after ILO-guided classification) to higher categories in a 15-year period was as high as >50%. Longer service duration and higher category of chest radiography at the previous health examination were the influential factors in determining the rapid progression of silicosis. The latter observation was confirmed also through a similar analysis on Group II workers. Whetstone preparations contained SiO2 by about 50%. No industrial hygiene data were available for both groups of stone cutters, but the exposure of Group I workers was estimated to be about 1 mg/m3, or well in excess of the current occupational exposure limit.
 ...
PMID:A 40-year follow-up of whetstone cutters on silicosis. 1272 66

The cumulative exposure to crystalline silica (SiO2) implies a linear relation between duration of exposure and SiO2 concentration, not always suitable to working situations of the last decades. A more correct definition of dose-response curve has currently to consider also different characteristics of SiO2, specifically: possible short-term increases in environmental SiO2 concentration, different mineralogical and surface properties of natural silica polymorphs, age of SiO2 particles, presence of contaminants on the surface of silica particles or even in the respirable fraction of total dust, respirable dust concentration in which SiO2 is diluted and other conditions, also affecting the host, able to slow alveolar clearance and lengthen permanence time of particles in the lung. Many models of definition of cumulative exposure so conceived have been proposed. However, to define the occupational risk threshold to contract silicosis and other silica-related diseases a number of models of cumulative exposure, i.e. biologically effective dose of SiO2, are likely to be delineated that take into account only factors specifically present in different occupational situations.
 ...
PMID:[Dose-response curve in the study of the effects of exposure to crystalline silica]. 1458 70

Work in Department of Energy (DOE) facilities has exposed workers to multiple toxic agents leading to acute and chronic diseases. Many exposures were common to numerous work sites. Exposure to crystalline silica was primarily restricted to a few facilities. I present the case of a 63-year-old male who worked in DOE facilities for 30 years as a weapons testing technician. In addition to silica, other workplace exposures included beryllium, various solvents and heavy metals, depleted uranium, and ionizing radiation. In 1989 a painful macular skin lesion was biopsied and diagnosed as leukocytoclastic vasculitis. By 1992 he developed gross hematuria and dyspnea. Blood laboratory results revealed a serum creatinine concentration of 2.1 mg/dL, ethrythrocyte sedimentation rate of 61 mm/hr, negative cANCA (antineutrophil cytoplasmic antibody cytoplasmic pattern), positive pANCA (ANCA perinuclear pattern), and antiglomerular basement membrane negative. Renal biopsy showed proliferative (crescentric) and necrotizing glomerulonephritis. The patient's diagnoses included microscopic polyangiitis, systemic necrotizing vasculitis, leukocytoclastic vasculitis, and glomerulonephritis. Environmental triggers are thought to play a role in the development of an idiopathic expression of systemic autoimmune disease. Crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma, systemic lupus erythematosus, rapidly progressive glomerulonephritis and some of the small vessel vasculitides. DOE workers are currently able to apply for compensation under the federal Energy Employees Occupational Illness Compensation Program (EEOICP). However, the only diseases covered by EEOICP are cancers related to radiation exposure, chronic beryllium disease, and chronic silicosis.
 ...
PMID:Silica exposure and systemic vasculitis. 1464 69

Quartz incubated in an aqueous solution of ascorbic acid is partially dissolved and the potential to generate hydroxyl radicals from hydrogen peroxide is enhanced. In order to investigate whether the surface activation triggered by the treatment with ascorbic acid would also involve an enhancement in cell toxicity, a murine macrophage cell line (RAW 264.7) was exposed to untreated and ascorbic acid-treated quartz. Ascorbic acid pretreated quartz was more toxic than untreated quartz and all cells died within 24 hours after exposure. Tetrandrine (a Chinese drug employed to retard or reverse fibrotic lesions of silicosis in humans) partially reduced cell toxicity generated by ascorbic acid pretreated quartz.
 ...
PMID:Crystalline silica incubated in ascorbic acid acquires a higher cytotoxic potential. 1465 13

Silicosis is a preventable occupational lung disease caused by inhaling dust containing crystalline silica; no effective treatment for silicosis is available. Deaths from inhalation of silica-containing dust can occur after a few months' exposure (1). Crystalline silica exposure and silicosis have been associated with work in mining, quarrying, tunneling, sandblasting, masonry, foundry work, glass manufacture, ceramic and pottery production, cement and concrete production, and work with certain materials in dental laboratories. To describe patterns of silicosis mortality in the United States, CDC analyzed data from the National Institute for Occupational Safety and Health (NIOSH) National Occupational Respiratory Mortality System (NORMS) for 1968-2002. This report summarizes the results of that analysis, which indicated a decline in silicosis mortality during 1968-2002 and suggested that progress has been made in reducing the incidence of silicosis in the United States. However, silicosis deaths and new cases still occur, even in young workers. Because no effective treatment for silicosis is available, effective control of exposure to crystalline silica in the workplace is crucial.
 ...
PMID:Silicosis mortality, prevention, and control--United States, 1968-2002. 1585 59

We compare the adsorption behavior of high density lipoproteins (HDL) and low density lipoproteins (LDL) on "fibrogenic" and "nonfibrogenic" mineral dusts. The adsorption tests with bovine lipoprotein concentrate and human serum produced the following results: 1) All seven examined fibrogenic dusts (SiO2 DQ12, SiO2 F600, silica, graphite, TiC, kaolin, talc) adsorbed significantly more high density lipoproteins (HDL), than the five examined nonfibrogenic (inert) dusts (TiO2, SnO2, Al2O3, Fe2O3, Fe3O4). This different behavior was particularly conspicuous in the presence of competing adsorbates (serum proteins). 2) In contrast, the adsorption of LDL did not correlate with the fibrogenicity of the mineral dusts. 3) The known silicosis-protective substance polyvinylpyridine-N-oxide inhibits the HDL adsorption of alpha-quartz. These results indicate that the adsorption of HDL could have a causal relationship with the triggering of a fibrotic reaction. The adsorption on the surface of fibrogenic dust particles provides an exceptional opportunity for the intake of HDL by macrophages. During the phagocytosis of the inhaled dust particles, the HDL adsorbed on the surface of the particles could be taken up by macrophages regardless of the receptor. There the HDL particles and/or compounds associated with them, such as lecithin-cholesterol-acyltransferase, could stimulate the macrophages to release fibrogenic mediators by some yet unknown mechanism.
 ...
PMID:Adsorption of lipoproteins onto mineral dust surfaces: a possible factor in the pathogenesis of particle-induced pulmonary fibrosis? 1632 Jun 25

Crystalline silica, known as a causal substance of silicosis, has been carefully evaluated for its carcinogenicity and fibrogenicity. In this study, we instilled crystalline silica of two different size (S(1.8) :1.80 microm (S.D. 2.0), S(0.7) :0.74 microm (S.D. 1.5)) into the trachea of rats to evaluate the size effects of the particles on pulmonary inflammation. S(1.8) and S(0.7) samples were administered to rats by a single intratracheal instillation (2 mg/ 0.4 ml saline). At three days, 1 wk and 1, 3 and 6 months after the instillation, the blood, bronchoalveolar lavage fluid (BALF), and pulmonary tissues were analyzed. Six images per HE-stained section were digitally captured and examined by the point counting method (PCM). Polymorphonuclear leukocyte (PMN)-in-blood specimens and cytospin specimens from BALF were stained immunohistochemically with BrdU. At six months after the instillation, the effects on inflammatory cells in the pulmonary tissues and BALF tended to be more marked in the rats instilled with S(1.8) than those instilled with S(0.7). Particularly, clear differences were observed in the number of inflammatory cells in BALF. Even if the particles are of the same chemical composition, the results suggest that, their biological effects vary depending on their particle size. Therefore, when such particles are used in workplaces, strict control systems should be established according to the risks present by different sizes of particles.
 ...
PMID:Effect of particle size of intratracheally instilled crystalline silica on pulmonary inflammation. 1742 65

Crystalline silica exposure can result in pulmonary fibrosis, where the pulmonary macrophage is key as a result of its ability to react to silica particles. In the mouse silicosis model, there is initial Th1-type inflammation, characterized by TNF-alpha and IFN-gamma. Previous studies determined that Th2 mediators (i.e., IL-13) are vital to development of pulmonary fibrosis. The present study, using in vivo and in vitro techniques, compares silica exposures between Balb/c and Th2-deficient mice in an effort to determine the link between Th2 immunity and silicosis. In long-term experiments, a significant increase in fibrosis and activated interstitial macrophages was observed in Balb/c but not IL-4Ralpha(-/-) mice. Additionally, a significant increase in Ym1 mRNA levels, a promoter of Th2 immunity, was determined in the interstitial leukocyte population of silica-exposed Balb/c mice. To elucidate the effects of silica on macrophage function, bone marrow-derived macrophages (BMdM) were exposed to particles and assayed for T cell (TC) stimulation activity. As a control, Ym1 mRNA expression in Balb/c BMdM was determined using IL-4 stimulation. In the in vitro assay, a significant increase in TC activation, as defined by surface markers and cytokines, was observed in the cultures containing the silica-exposed macrophages in wild-type and IL-4Ralpha(-/-) mice, with one exception: IL-4Ralpha(-/-) BMdM were unable to induce an increase in IL-13. These results suggest that crystalline silica alters cellular functions of macrophages, including activation of TC, and that the increase in Th2 immunity associated with silicosis is via the IL-4Ralpha-Ym1 pathway.
 ...
PMID:The IL-4Ralpha pathway in macrophages and its potential role in silica-induced pulmonary fibrosis. 1805 81

Historical studies report that cellular injury and silicosis are related to cytosolic free calcium (Ca2+). Moreover, reactive oxygen species (ROS) have been linked to cellular injury. However, the detail mechanism of the increase in [Ca2+]i and the relationship between [Ca2+]i and ROS production remains unknown. Quartz particle has been found to increase [Ca2+]i and activate the generation of ROS. Our hypothesis is that [Ca2+]i increase induced by quartz particle is from extracellular Ca2+ through the Ca2+ channel, and [Ca2+]i increase is believed to activate ROS production. In order to examine this hypothesis, we treated rat alveolar macrophages with quartz (SiO2) particles and used laser scanning confocal microscopy to measure [Ca2+]i and the fluorescence intensity of ROS. Time- and dose-dependent increases in [Ca2+]I and ROS in macrophages as well as cell viability were observed. Through chelating extracellular Ca2+ with ethylene glycol tetraacetic acid and releasing intracellular Ca2+ with thapsigargin, we found that 72.7% of the [Ca2+]i increase was due to the influx of Ca2+ from the extracellular environment, via Ca2+ channels in the plasma membrane. By adding mannitol to scavenge hydroxyl radicals (OH(.)), and removing surface iron from the quartz particles to reduce OH(.) generation, we observed a reduced level of ROS generation, whereas the increase in [Ca2+]i was unaffected. When using EGTA to reduce [Ca2+]i, we observed a decrease in ROS production. This study suggests that the [Ca2+]i influx was independent of OH(.) production, and the [Ca2+]i increase resulted in ROS production. These results further indicate that there is a strong relationship between cytosolic free Ca2+ content and cellular injury as well as silica exposure.
 ...
PMID:Intracellular influx of calcium induced by quartz particles in alveolar macrophages. 1983

"Vitreous silica" is a particular form of amorphous silica, much neglected in experimental studies on silica toxicity. In spite of the incorrect term "quartz glass", often employed, this material is fully amorphous. When reduced in powdered form by grinding, the particulate appears most close to workplace quartz dust but, opposite to quartz, is not crystalline. As silicosis and lung cancer are also found among workers exposed to "quartz glass", the question arises of whether crystallinity is the prerequisite feature that makes a silica dust toxic. We compare here the behavior of comminuted quartz, vitreous silica, and monodispersed silica spheres, as it concerns surface reactivity and cellular responses involved in the accepted mechanisms of silica toxicity. Care was taken to choose samples of extreme purity, to avoid any effect due to trace contaminants. Quartz and vitreous silica, opposite to silica spheres, show irregular particles with sharp edges, stable surface radicals, and sustained release of HO(*) radicals via a Fenton-like mechanism. The evolution of the heat of adsorption of water as a function of coverage shows with quartz and vitreous silica a similar pattern of strong hydrophilic sites, nearly absent on the other silica specimen. When tested on a macrophage cell line (MH-S), vitreous silica and pure quartz, but not the monodispersed silica spheres, showed a remarkable potency in cytotoxicity, nitric oxide synthase activation and release of nitrite, and tumor necrosis factor-alpha production, suggesting a common behavior in inducing an oxidative stress. All of the above features appear to indicate that crystallinity might not be a necessary prerequisite to make a silica particle toxic.
 ...
PMID:Does vitreous silica contradict the toxicity of the crystalline silica paradigm? 2008 95


<< Previous 1 2 3 4 5 6 7 Next >>