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

Silica-induced lung injury and the development of silicosis is one of the major occupational diseases. Accumulation and deposition of respirable dust containing silica mineral particles in the lung produces chronic lung disease characterized by granulomatous and fibrotic lesions. Knowledge of precise mechanisms, which induce this process is still limited, hence problems faced in the treatment of silicosis, especially the casual one. This article describes various trials of casual silicosis treatment with tetrandrine (Tet), isolated from the root of Stephania tetrandra, tumor necrosis factor (TNF) antagonists, polyvinyl-pyridine-N-oxide (PVNO), aluminum compounds, corticosteroids or bronchoalveolar lavage (BAL). The existing methods are not sufficient, which warrants further investigations. At present, prevention of the disease and treatment of its complications are most important.
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PMID:[Trials of casual treatment of silicosis]. 1712 34

Silica particle-associated inflammation is implicated in the genesis of several pulmonary diseases, including silicosis and lung cancer. In this study we investigated the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in silica-stimulated induction of TNF-alpha and IL-1beta and how PC-PLC activity is regulated by silica in a rat alveolar macrophage model. We demonstrated that inhibition of PC-PLC, which was achieved with tricychodecan-9-yl-xanthate (D609), blocked the silica-stimulated induction of TNF-alpha and IL-1beta in alveolar macrophage, suggesting that PC-PLC is involved in the silica-associated inflammatory response. PC-PLC activity was increased significantly by silica exposure, and this could be inhibited by MnTBAP, which catalyzes both the dismutation of O2.- to O2 and H2O2 and the dismutation of H2O2 to O2 and H2O, revealing that PC-PLC activity is regulated in a redox-dependent manner. This is further confirmed by the finding that PC-PLC activity was increased by exogenous H2O2. The intracellular calcium chelator BAPTA blocked the H2O2-increased PC-PLC activity, while the calcium ionophore, A23187, enhanced PC-PLC activity. The data indicate that PC-PLC plays critical roles in the silica-associated inflammatory response and that PC-PLC is regulated through redox- and calcium-dependent manners in alveolar macrophages.
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PMID:Silica induces macrophage cytokines through phosphatidylcholine-specific phospholipase C with hydrogen peroxide. 1715 58

Arginase induction was reported in several inflammatory lung diseases, suggesting that this may be a common feature underlying the pathophysiology of such diseases. As little is known regarding arginase expression in silicosis, the induction and cellular localization of arginase were elucidated in lungs of Sprague-Dawley rats 24 h following exposure to varying doses of silica by intratracheal instillation. Arginase expression was evaluated by activity assay, quantification of arginase I and arginase II mRNA levels using real-time polymerase chain reaction (PCR), and immunohistochemistry. Analyses of cells and fluid obtained by bronchoalveolar lavage (BAL) showed that markers of pulmonary inflammation, tissue damage, activation of alveolar macrophages (AM) and NO production were significantly increased by all silica doses. Arginase activity was increased also in AMs isolated from BAL fluid of silica-treated rats. Silica produced two- and three-fold increases in arginase activity of whole lung at doses of 1 and 5 mg/100 g body weight, respectively. Levels of arginase I mRNA, but not of arginase II mRNA, were similarly elevated. In control lungs, arginase I immunoreactivity was observed only in AMs sparsely dispersed throughout the lung; no inducible nitric oxide synthase (iNOS) immunoreactivity was detected. In silica-treated lungs, arginase I and iNOS were co-expressed in most AMs that were abundantly clustered at inflammatory foci. The rapid induction of arginase I expression in inflammatory lung cells, similar to induction of arginase in other inflammatory lung diseases, implicates elevated arginase activity as a factor in the development of lung damage following exposure to silica.
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PMID:Cell- and isoform-specific increases in arginase expression in acute silica-induced pulmonary inflammation. 1736 72

Evidence suggests that short-term animal exposures to synthetic amorphous silicas (SAS) and crystalline silica can provide comparable prediction of toxicity to those of 90-day studies, therefore providing the opportunity to screen these types of substances using short-term rather than 90-day studies. To investigate this hypothesis, the inhalation toxicity of three SAS, precipitated silica Zeosil 45, silica gel Syloid 74, and pyrogenic silica Cab-O-Sil M5 was studied in Wistar rats. Rats were exposed nose-only to concentrations of 1, 5 or 25mg/m(3) of one of the SAS 6h a day for five consecutive days. Positive controls were exposed to 25mg/m(3) crystalline silica (quartz dust), negative controls to clean air. Animals were necropsied the day after the last exposure or 1 or 3 months later. All exposures were tolerated without serious clinical effects, changes in body weight or food intake. Differences in the effects associated with exposure to the three types of SAS were limited and almost exclusively confined to the 1-day post-exposure time point. Silicon levels in tracheobronchial lymph nodes were below the detection limit in all groups at all time points. Silicon was found in the lungs of all high concentration SAS groups 1-day post-exposure, and was cleared 3 months later. Exposure to all three SAS at 25mg/m(3) induced elevations in biomarkers of cytotoxicity in bronchoalveolar lavage fluid (BALf), increases in lung and tracheobronchial lymph node weight and histopathological lung changes 1-day post-exposure. Exposure to all three SAS at 5mg/m(3) induced histopathological changes and changes in BALf only. With all three SAS these effects were transient and, with the exception of slight histopathological lung changes at the higher exposure levels, were reversible during the 3-month recovery period. No adverse changes were observed in animals exposed to any of the SAS at 1mg/m(3). In contrast, with quartz-exposed animals the presence of silicon in the lungs was persistent and toxicological effects differed from those seen with SAS both with regard to the type and severity as well as in the time-response profile. In quartz-exposed animals silicon in the tracheobronchial lymph nodes was below the detection limit but silicon was found in the lungs at comparable levels 0-, 1- and 3-months post-exposure. One-day post-exposure to quartz, elevations in biomarkers of cytotoxicity in BALf, increases in lung and tracheobronchial lymph node weight and histopathological lung changes were minimal. These effects were present at 1-month post-exposure and progressively more severe at 3-months post-exposure. Overall, the results of the current study are similar to those of other published studies that had a 90-day exposure period and both types of studies indicate that the lack of lung clearance is a key factor in the development of silicosis.
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PMID:Five-day inhalation toxicity study of three types of synthetic amorphous silicas in Wistar rats and post-exposure evaluations for up to 3 months. 1752 41

Inhalation of silica, without evidence of silicosis, is believed to predispose individuals to bacterial infections and impair respiratory immune functions. Silica may alter the sensitivity of antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs), to other types of infection; however, the exact nature of these exchanges remains uncertain. The purpose of the present study is to characterize the effect of silica exposure on innate pulmonary defense mechanisms following Toll-like receptor (TLR) ligand-induced activation using DCs as a model APC and determine whether these signals act in synergy or opposition to one another. Using C57Bl/6 mice, pattern recognition receptor expression on DCs was examined in vitro and in vivo using flow cytometry, and the activation state of pulmonary and granulocyte-macrophage colony-stimulating factor-derived DCs was assessed in response to silica in combination with TLR ligands (lipopolysaccharide, cytosine-phosphate-guanine, or polyinosinic:polycytidylic acid) using flow cytometry and measurement of cytokine production. In this study, silica attenuated TLR ligand-dependent DC activation with regards to accessory molecule expression as well as nitric oxide and inflammatory cytokine production. Furthermore, silica's ability to modulate TLR ligand-dependent DC activation did not appear to be dependent on the class A scavenger receptors. Taken together, silica's ability to alter susceptibility to infection may be due to impaired inflammatory responses and reduced antibacterial activity.
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PMID:Silica suppresses Toll-like receptor ligand-induced dendritic cell activation. 1818 Mar 31

Silicosis has progressive, but unpredictable development. There are no markers routinely available to measure the activity and prognosis of silicosis. 8-isoprostane, a marker of oxidative stress and leukotrienes B4, C4, D4, and E4 were measured in exhaled breath condensate in patients with silicosis. Sixty subjects were examined, with mean age 66.7+/-2.0 yr and mean exposure to silica 23.6+/-2.5 yr. The control group had 25 subjects, with mean age 64.7+/-4.8 yr. Exhaled breath was collected using the EcoScreen (Jaeger, Germany); 8-isoprostane and leukotrienes were analyzed by high-performance liquid chromatography/mass spectrometry. Several lung functions parameters were impaired in silicotics in comparisons with the controls; ESR, alpha1-antitrypsin and proteinuria were higher in the silicotics. Antineutrophilic cytoplasmic antibodies were more frequent in the silicotics (39%) than in the controls (4%), (p=0.0017). The mean level of 8-isoprostane in the patients with silicosis was 73.6+/-9.9 vs. 43+/-10 pg/ml (p=0.0001) in the controls. Silica exposure category (high, medium, none) was positively associated with the level of 8-isoprostane. In the patients with complicated silicosis, a high level of 8-isoprostane was found more frequently (p=0.0194). Leukotriene D4 was also increased in the silicotics (21.1+/-2.7 pg/ml) vs. the controls (14.7+/-2.7 pg/ml), (p=0.001). No significant effect of smoking or alcohol consumption on the markers examined was seen. This is the first study using exhaled breath condensate analysis in patients with silicosis.
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PMID:8-isoprostane and leukotrienes in exhaled breath condensate in Czech subjects with silicosis. 1821 71

The small dimension and particle shape of silica in gypsum used to prepare moulds for lost wax casting might be responsible for the high prevalence of silicosis in gold jewellery. To test this hypothesis, human pulmonary epithelial cell (BEAS-2B) cultures were exposed to two samples of silica with different crystal micro-morphologies: Silica Powder (Silica P) which is used in casting gold jewellery, and no powder Silica (Silica F). Extracellular matrix (ECM) production was evaluated using radio-labelled precursors and quantified by RT-PCR analysis. Expression of basic fibroblast growth factor (FGF2) and its receptor (FGFR2) was also evaluated. The results demonstrated Silica P particles had a very fine lamellar crystalline structure while Silica F was characterized by larger rounded crystals. Silica P stimulated collagen production significantly more than Silica F and downregulated laminin and metalloprotease expression. Both silica samples down-regulated FGF2 but only Silica F enhanced FGF2 receptor expression. In conclusion each Silica sample promoted a profibrotic lung microenvironment in a different manner and also elicited different FGF2 signalling pathways. The data confirm that different micromorphology of Silica particles affects the fibrogenic potential and the molecular mechanisms of dust pathogenicity.
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PMID:Comparative in vitro studies on the fibrogenic effects of two samples of silica on epithelial bronchial cells. 1826 Dec 61

Silica dust particles in the form of quartz (but not kaolin) have been hypothesized to promote pulmonary diseases such as silicosis. The hypothesis is that quartz and kaolin have a comparable membranolytic potential on a specific surface area basis, and they have a comparable cytotoxic potential for lavaged pulmonary macrophages. Suppression of the cytotoxic activity occurs when these dust particles are treated with dipalmitoylphosphatidylcholine (DPPC), a common phospholipid component of the lung pulmonary surfactant. However, the enzyme phospholipase A2 is known to digest the phospholipid component more readily in the presence of quartz than kaolin. Since surface silanol (Si-OH) and aluminol (Al-OH) groups may interact differently with the phospholipid, an understanding of the selective removal of phospholipid by PLA2 may explain in vivo differences in cytotoxicity between quartz and kaolin. To develop some insight into this phenomenon, the interaction between a phospholipid and silica particles was examined by performing ab initio DFT calculations on clusters constructed with small (one or two silica tetrahedral units) representative parts of the silicate surface and the phospholipid head group. The clusters consisted of a phospholipid head group or functional groups from the head group complexed with Si(OSiH 3) 3OH, Al(OSiH 3) 3OH (-) or Al(OSiH 3) 3OH 2. Fully optimized geometries of the complexes were used to determine binding energies, -OH vibrational frequency shifts, and NMR chemical shieldings. Results indicate that interaction of the protonated aluminol group (Al-OH 2 (+)) with the phosphate portion of the head group is strongest, while interaction of the -OH 2 (+) group with the trimethyl-choline moiety of the head group is weakest. The presence of the choline moiety increased the magnitude of the -OH vibrational frequency shifts, and the shifts were significantly larger in complexes with protonated aluminol groups relative to silanol complexes. Analysis of ChelpG atomic charges shows that a net transfer of charge occurs from the silica unit to the head group within the complexes.
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PMID:Interaction of the phospholipid head group with representative quartz and aluminosilicate structures: an ab initio study. 1847 31

Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration > or = 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.
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PMID:Tuberculosis and silicosis: epidemiology, diagnosis and chemoprophylaxis. 1909 4

The objective of this study was to investigate potential role of taurine and niacin supplementation, and their combination, in an in vitro model of silica-induced, macrophage-mediated pulmonary fibroblast proliferation. Human monocytic cell line (THP-1 cell) was primed to differentiation into macrophages by phorbol myristate acetate (PMA). PMA-primed THP-1 cells were subjected to silicon dioxide exposure. Other PMA-primed THP-1 cells incubated with taurine and niacin concentration gradients, respectively, and then were treated with silicon dioxide for 6 hours. Collected THP-1 supernatants preconditioned with taurine and niacin gradients were added to human pulmonary WI-38 cells to evaluate proliferative activity. Transforming growth factor (TGF)-beta1 mRNA in macrophages and protein level in supernatant were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Taurine- and niacin-preconditioned macrophages were more resistant to silica-induced TGF-beta1 up-regulation than macrophages without precondition. Furthermore, medium conditioned with supernatant from silica-exposed macrophages following taurine and niacin pretreatment could facilitate inhibition of pulmonary fibroblast proliferation. Moreover, the above effects could be accentuated by the combination of taurine and niacin. Down-regulation of TGF-beta 1 expression in macrophages by taurine and niacin could attenuate silica-induced pulmonary fibroblasts proliferation in vitro, which may be of therapeutic potential for early stage silicosis.
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PMID:Attenuation of silica-induced pulmonary fibroblasts proliferation by taurine and niacin in vitro. 1933 3


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