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[Graft polymerization onto poly(methylvinylsiloxane)-bonded silica gel by gamma-ray irradiation].

Poly(methylvinylsiloxane)-bonded silica gel was synthesized by condensation reaction between silica gel and the hydrolysis product of methylvinyldichlorosilane. Graft polymerization of styrene or indene onto poly(methylvinylsiloxane)-bonded silica gel was carried out by gamma-ray irradiation and compared with that onto silica gel. Homopolymer was found to be formed through a radical mechanism concurrently with an ionic mechanism in the graft polymerization. Probably genuine graft polymers are formed in the graft polymerization onto poly(methylvinylsiloxane)-bonded silica gel, while the product formed in the graft polymerization onto silica gel may be apparent graft polymers.

Gamma Rays↗

Development of quantitative exposure data for a pooled exposure-response analysis of 10 silica cohorts.

BACKGROUND: Comprehensive quantitative silica exposure estimates over time, measured in the same units across a number of cohorts, would make possible a pooled exposure-response analysis for lung cancer. Such an analysis would help clarify the continuing controversy regarding whether silica causes lung cancer. METHODS: Existing quantitative exposure data for 10 silica-exposed cohorts were retrieved from the original investigators. Occupation- and time-specific exposure estimates were either adopted/adapted or developed for each cohort, and converted to milligram per cubic meter (mg/m(3)) respirable crystalline silica. RESULTS: Quantitative exposure assignments were typically based on a large number (thousands) of raw measurements, or otherwise consisted of exposure estimates by experts (for two cohorts). Median exposure level of the cohorts ranged between 0.04 and 0.59 mg/m(3) respirable crystalline silica. Exposure estimates were partially validated via their successful prediction of silicosis in these cohorts. CONCLUSIONS: Existing data were successfully adopted or modified to create comparable quantitative exposure estimates over time for 10 silica-exposed cohorts, permitting a pooled exposure-response analysis. The difficulties encountered in deriving common exposure estimates across cohorts are discussed.

Cohort Studies↗

One agent, many diseases: exposure-response data and comparative risks of different outcomes following silica exposure.

BACKGROUND: Evidence in recent years indicates that silica causes lung cancer, and probably renal disease, in addition to its well-known relationship to silicosis. There is also suggestive evidence that silica can cause arthritis and other auto-immune diseases. Silica has, therefore, joined a handful of other toxic exposures such as tobacco smoke, dioxin, and asbestos which cause multiple serious diseases. METHODS: The available exposure-response data for silica and silicosis, lung cancer, and renal disease are reviewed. We compare the corresponding excess risks (or absolute risks in the case of silicosis) of death or disease incidence by age 75 for these three diseases, subsequent to a lifetime (45 years) of exposure to silica at current US standard (0.1 mg/m(3) respirable crystalline silica). RESULTS: The absolute risk of silicosis, as defined by small opacities greater than or equal to ILO classification 1/1 on an X-ray, ranges from 47% to 77% in three cohort studies with adequate follow-up after employment. The absolute risk of death from silicosis is estimated at 1.9% (0.8%-2.9%), based on a pooled analysis of six cohort studies. The excess risk of lung cancer death, assuming US male background rates, is 1.7% (0.2%-3.6%), based on a pooled analysis of ten cohort studies. The excess risk of end-stage renal disease (assuming male background rates) is 5.1% (2.2%-7.3%), based on a single cohort. The excess risk of death from renal disease is estimated to be 1.8% (0.8%-9.7%), based on a pooled analysis of three cohorts. CONCLUSIONS: Keeping in mind that the usual OSHA acceptable excess risk of serious disease or death for workers is 0.1%, it is clear that the current standard is far from sufficiently protective of workers' health. Perhaps surprisingly, kidney disease emerges as perhaps a higher risk than either mortality from silicosis or lung cancer, although the data are based on fewer studies.

Adult↗

Metal and non-metal miners' exposure to crystalline silica, 1998-2002.

BACKGROUND: Crystalline silica is well known to cause silicosis and other diseases. Exposure is common in the mining industry and consequently, the US Mine Safety and Health Administration (MSHA) evaluates miners exposure to silica to determine compliance with its exposure limit. METHODS: MSHA exposure measurements were obtained for the 5-year period from 1998 to 2002 and average exposure was calculated classified by occupation and by mine. Evaluation criteria were whether average values exceeded MSHA's permissible exposure limit or the limit recommended by the National Institute for Occupational Safety and Health (NIOSH), whether there was a risk of exposure to freshly fractured silica, and whether there was a risk of a high rate of exposure to silica. RESULTS: Miners in certain jobs are exposed to silica above permissible and recommended exposure limits. Some miners may also be exposed at a high rate or to freshly fractured silica. CONCLUSIONS: Known dust control methods should be implemented and regular medical surveillance should be provided.

Air Pollutants, Occupational↗

Exposure to silica and risk of ANCA-associated vasculitis.

BACKGROUND: Exposure to silica dust is considered to be one of etiological factors of antineutrophil cytoplasmic antibodies (ANCA) -associated vasculitis (AAV). METHODS: Subjects exposed to silica dust in Central Bohemia and followed in the Department of Occupational Medicine, Charles University, were selected for study. A group of 86 men exposed to SiO2 for at least 5 years were examined. The association between occupational exposure to silica dust and ANCA positivity is analyzed. RESULTS: The subjects had a mean age of 66.7 years, and mean exposure to silica of 22.3 years. ANCA were detected significantly more frequently in patients group (17.1%; P-ANCA 18x, C-ANCA 3x) than in controls (n = 28, mean age 64.2 years, P-ANCA 1x, i.e., 3.6%). ANCA positivity was found less frequently (7.1%) in the group with history of SiO2 exposure without signs of pronounced silicosis, than in the group with simple (30.3%) or complicated silicosis (36.0%). Odds ratio for ANCA positivity and relative risk estimate in patients with silicosis were highly significant. Among possible predictor factors for ANCA positivity, silicosis and tuberculosis were relevant. No typical AAV was present among the patients. CONCLUSION: Long-term silica exposure may be one of the exogenous factors contributing to ANCA production, however, silica exposure alone, without typical silicosis, was not associated with ANCA positivity.

Adult↗

An approach to the characterization of silica exposure in U.S. industry.

Quantitative evaluation of worker exposure to silica in nine Standard Industrial Classification (SIC) codes was conducted, using data derived from OSHA compliance inspections, in order to assess the silica exposure problem in the U.S. The nine SICs studied were those in which OSHA inspections were concentrated. They include: construction; chemical manufacture; stone, glass, and clay manufacturing; primary metal industries; metal fabrication; machinery; transportation; and miscellaneous manufacturing industries. High exposures to silica were documented in each industry, with the number of test samples over the permissible exposure limit ranging from 14% (aluminum foundries) to 73% (pottery). An estimation is made that 24,889 workers employed in ferrous and nonferrous foundries are at risk of silica-related pulmonary effects. The data developed in this analysis also indicate the need to investigate certain industries that had high exposures but few inspections. The limitations of the data base for estimating the scope of the silica problem, including lack of data on mining and milling, are discussed. We conclude that exposure to silica represents a continuing and significant problem in a number of U.S. industries.

Air Pollutants, Occupational↗

Estimating historical exposure to silica among mine and pottery workers in the People's Republic of China.

A quantitative retrospective exposure assessment method was developed for use in a nested case-control study of lung cancer among mine and pottery workers exposed to silica dust in the People's Republic of China. Exposure assessment was carried out in 20 mines (10 tungsten, 6 iron/copper, and 4 tin) and nine pottery factories. A job title dictionary was developed and used in both the collection of historical exposure information and work histories of 1,668 (316 cases and 1,352 controls) study subjects. Several data abstraction forms were developed to collect historical and current exposure information and employees' work histories, starting in 1950. A retrospective exposure matrix was developed on the basis of facility/job title/calendar year combinations using available historical exposure information and current exposure profiles. Information on the amount of respirable, thoracic, and free silica content in total dust was used in estimating exposure to silica. Starting in 1950, 6,805 historical estimates had been carried out for 14 calendar-year periods. We estimated the average total dust concentration to be 9 mg/M3, with a range from 28 mg/M3 in earlier years to 3 mg/M3 in recent years. Several exposure indices [such as cumulative dust, average dust, cumulative respirable (< 5 mu in particle size) and thoracic (< 10 mu in particle size) silica dust, average respirable and thoracic silica dust, exposure-weighted duration, and the highest/longest exposure] were calculated for individuals by merging work history and historical exposure matrix for each study subject. We developed these various measures of exposure to allow investigators to compare and contrast different indices of historical exposure to silica.

Case-Control Studies↗

Occupational silica and solvent exposures and risk of systemic lupus erythematosus in urban women.

OBJECTIVE: To assess the risk of systemic lupus erythematosus (SLE) associated with occupational exposure to silica dust and organic solvents in an urban population. METHODS: Women with SLE were identified through both community screening and hospital databases in 4 predominantly African American neighborhoods in Boston. Female control patients were volunteers from the same communities and were screened for the absence of connective tissue disease. Demographic factors, smoking history, and a detailed occupational history, including exposures to specific chemicals, were obtained by in-person interviews. The exposure assessment was based on independent evaluation of the occupational history by 2 reviewers who were blinded to each subject's disease status. The risks associated with exposure to silica and solvents were analyzed using multivariate conditional logistic regression models, adjusted for potential confounders. RESULTS: Ninety-five patients and 191 age- and race-matched controls were included in this analysis. Exposure to silica for longer than 1 year was associated with SLE (odds ratio [OR] 4.3, 95% confidence interval [95% CI] 1.7-11.2). An exposure-response effect was seen for longer duration of exposures to silica (P for trend = 0.01). The association between occupational exposure to organic solvents and SLE was not statistically significant (OR 1.04, 95% CI 0.34-3.2). CONCLUSION: Silica exposure from a variety of industrial occupations in urban areas is associated with an increased risk of SLE. A longer duration of exposure to silica dust is associated with greater risks. This study provides further impetus for additional research into the influence of modifiable exposures on the pathogenesis of SLE.

Adult↗

The Si-tag for immobilizing proteins on a silica surface.

Targeting functional proteins to specific sites on a silicon device is essential for the development of new biosensors and supramolecular assemblies. Using intracellular lysates of several bacterial strains, we found that ribosomal protein L2 binds tightly to silicon particles, which have surfaces that are oxidized to silica. A fusion of E. coli L2 and green fluorescence protein adsorbed to the silica particles with a K(d) of 0.7 nM at pH 7.5 and also adsorbed to glass slides. This fusion protein was retained on the glass slide even after washing for 24 h with a buffer containing 1 M NaCl. We mapped the silica-binding domains of E. coli L2 to amino acids 1-60 and 203-273. These two regions seemed to cooperatively mediate the strong silica-binding characteristics of L2. A fusion of L2 and firefly luciferase also adsorbed on the glass slide. This L2 silica-binding tag, which we call the "Si-tag," can be used for one-step targeting of functional proteins on silica surfaces.

Bacterial Proteins↗

Silica pattern formation in diatoms: species-specific polyamine biosynthesis.

Diatoms are eukaryotic, unicellular algae that are well known for the intricate architecture of their silica-based cell walls. Species identification is mainly based on variations of their hierarchically organized silica structures. Particularly striking silica frameworks are found among diatoms that belong to the genus Coscinodiscus. Recent work indicates an important role for long-chain polyamines in guiding silica precipitation as well as in silica-pattern formation. Here we demonstrate that polyamines, even if isolated from closely related diatom species, exhibit substantial structural differences. Structural variations include the overall chain length, the degree of methylation, positions of secondary amino functionalities, and, unexpectedly, site-specific incorporation of a quaternary ammonium functionality. These findings support a specific role for polyamines in creating silica nanostructures.

Biogenic Polyamines↗

Silica-based monoliths for capillary electrochromatography: methods of fabrication and their applications in analytical separations.

This review article is intended to provide the reader with the recent advances made in the fabrication of silica-based monolithic capillary columns for use in capillary electrochromatography (CEC). The silica-based monoliths can be produced by three different approaches, namely (i) fusion of silica particles by thermal sintering, (ii) cross-linking/entrapping silica particles in a packed bed using the sol-gel process, and (iii) polymerization of silicon alkoxide precursors using the sol-gel process. Thus far, approach (iii) is the most widely used for fabricating silica monoliths. After providing a thorough description of each of the three approaches used for the production of silica-based monolithic capillary columns, the analytical separations performed by CEC on each kind of monolith are discussed.

Chromatography, Micellar Electrokinetic Capillary↗

Room-temperature preparation and characterization of poly (ethylene glycol)-coated silica nanoparticles for biomedical applications.

Monodisperse, spherical, polyethylene glycol (PEG)-coated silica nanoparticles have been prepared at room temperature and characterized for the purpose of biomedical applications. The particles were synthesized by the hydrolysis of tetramethyl orthosilicate (TMOS) in alcohol media under catalysis by ammonia, and their size can range from about 50-350 nm in diameter. We studied the particle size and size distribution using a scanning electron microscope (SEM) and an asymmetric field-flow fractionation (AFFF) multiangle static light-scattering instrument. The chemical and/or physical binding of PEG to the silica nanoparticles was studied by infrared spectroscopy, and the weight percentage of PEG attached to the particles was quantified. The PEG-coated silica nanoparticles showed enhanced colloidal stability when redispersed into aqueous solutions from the dried state as a result of the steric stabilization function of the PEG polymer grafted on the surface of particles. A nonspecific protein-binding test was also carried out to show that the PEG coating can help reduce the protein adsorption onto the surface of the particles, relating to the biocompatibility of these PEG-coated particles. Also, the inclusion of magnetic nanoparticles into the silica particles was shown as an example of the possible applications of PEG-coated silica particles. These silica nanoparticles, as a matrix for encapsulation of certain reagents, have potential for applications to in vivo diagnosis, analysis, and measurements inside intact biologic systems.

Biocompatible Materials↗

Enhanced secretion of immunoreactive bombesin by alveolar macrophages exposed to silica.

Bombesin has recently been identified in alveolar macrophages (AM). Since this peptide has been shown to stimulate fibroblast growth in culture, we wished to determine whether AM exposed to the fibrogenic particle silica in vivo were capable of secreting more bombesin than AM recovered after instilling inert carbon particles to the lung. Rats received 10 mg of either carbon or silica by intratracheal injection and were killed at 3 days or 6 weeks. Both particles induced a rapid inflammatory response, and normal levels of immunoreactive bombesin were measured in lung lavage fluid and in freshly recovered macrophages from all rats. However, incubation of normal AM for 4 h in serum free medium produced a significant increase in bombesin levels measured in supernatants. Bombesin in supernatants of AM cultured after recovery from rats exposed to carbon was at the control value, while AM recovered after silica exposure in vivo secreted increased amounts of bombesin when cultured. Cells recovered 6 wk after instilling silica to the lung and cultured for 4 h secreted 50% more bombesin than control AM. At this time, hydroxyproline measured in the silica-injected lungs was also significantly higher than in controls or carbon-injected rats. These results indicate that AM recovered from lungs after exposure to silica secrete increased amounts of bombesin during the development of pulmonary fibrosis.

Animals↗

Macrophages from C3H/HeJ mice require an additional step to produce monokines: synergistic effects of silica and poly(I:C) in the release of interleukin 1.

Resident macrophages from C3H/HeJ mice, in contrast with those of other strains of mice such as BDF1 mice, did not release a 35 kD m.w. factor having macrophage replacing activity (FRM) or interleukin 1 (IL-1) when, respectively, cultured alone or in the presence of silica. C3H/HeJ macrophages were nevertheless capable of producing an intracellular IL-1-like activity. In addition, after a two-step activation process, macrophages from BDF1 mice spontaneously released IL-1, whereas silica was required to induce the release of IL-1 from similarly treated C3H/HeJ macrophages. Such in vivo primed and in vitro stimulated macrophages failed to release FRM. In contrast, poly(I:C) was able to induce the release of FRM by C3H/HeJ macrophages but not that of IL-1; moreover, the addition of silica to poly(I:C)-stimulated cells led to an IL-1 release similar to that obtained with normal mice treated with silica alone. Since poly(I:C) is able to elicit the production of interferons (IFN), the involvement of IFNs was investigated in poly(I:C) activity. Neither IFN-alpha/beta nor IFN-gamma, when used alone or in the presence of silica, could induce the release of IL-1 by C3H/HeJ macrophages. In addition, antibodies to IFN-alpha/beta and IFN-gamma were unable to affect the poly(I:C) and silica induced release of IL-1. Thus, the signal provided by poly(I:C) does not appear to be mediated by IFN(s).

Animals↗

Silica-exposed macrophages release a growth-promoting activity for type II pneumocytes.

This study addresses the hypothesis that silica-activated alveolar macrophages could release soluble factors stimulating type II cell proliferation. Macrophages from control sheep were exposed or not in vitro to silica, aluminum-treated silica (Si-Al), or titanium dioxide (TiO2). In addition, macrophages from a model of chromic silica-exposed sheep were studied. Supernatants from unstimulated macrophages were found to double basal type II cell DNA synthesis. Alveolar macrophage-conditioned media (AMCM) collected from cells exposed in vitro to silica induced an additional growth-promoting activity for type II cells. Supernatants from Si-Al- or TiO2 dust-exposed alveolar macrophages had the same effects as unstimulated AMCM. In addition, AMCM from in vivo silicotic sheep cells also contained elevated levels of type II cell mitogenic activity. These results suggest that in vitro as in vivo, silica-activated macrophages produce a type II cell growth factor(s) for type II epithelial cells.

Animals↗

Silica induces apoptosis in macrophages and the release of interleukin-1 alpha and interleukin-1 beta.

Resident adherent peritoneal cells selectively released high amounts of interleukin-1 (IL-1) activity when treated with silica. The use of anti-IL-1 antisera showed that both IL-1 alpha and IL-1 beta were present in supernatants of silica-treated macrophages. In contrast, intracellular IL-1 activity was totally neutralized by anti-IL-1 alpha antibodies and was easily converted into the mature IL-1 alpha form by autolysis in cytoplasmic extracts. Anion exchange chromatography clearly separated the two IL-1 species present in supernatants of silica-stimulated macrophages. Natural IL-1 beta was further characterized by chromatofocalization; it had an apparent isoelectric point, pI, in the range 8.3-8.6. In agreement with previous findings showing that IL-1 beta was released only by apoptotic cells, we have found that silica-treated macrophages underwent apoptosis. This was demonstrated by the characteristic laddering electrophoretic pattern of DNA extracted from silica-treated cells and by the morphology of macrophage nuclei stained with the DNA-specific dye DAPI. In addition, quantification of apoptotic cells was performed by a flow cytometric analysis based on the reduction of cellular DNA content exhibited by apoptotic cells. Treatment of macrophages with silica, therefore, results in an active process that promotes the processing and liberation of IL-1 beta.

Animals↗

Short communication performance of octadecylsilylated monolithic silica capillary columns of 530 microm inner diameter in HPLC.

Monolithic silica capillary columns were successfully prepared in a fused silica capillary of 530 microm inner diameter and evaluated in HPLC after octadecylsilylation (ODS). Their efficiency and permeability were compared with those of columns pakked with 5-microm and 3-microm ODS-silica particles. The monolithic silica columns having different domain sizes (combined size of through-pore and skeleton) showed 2.5-4.0-times higher permeability (K= 5.2-8.4 x 10(-14) m2) than capillary columns packed with 3-mm particles, while giving similar column efficiency. The monolithic silica capillary columns gave a plate height of about 11-13 microm, or 11 200-13 400 theoretical plates/150 mm column length, in 80% methanol at a linear mobile phase velocity of 1.0 mm/s. The monolithic column having a smaller domain size showed higher column efficiency and higher pressure drop, although the monolithic column with a larger domain size showed better overall column performance, or smaller separation impedance (E value). The larger-diameter (530 microm id) monolithic silica capillary column afforded a good peak shape in gradient elution of proteins at a flow rate of up to 100 microL/min and an injection volume of up to 10 microL.

Journal Article↗

Nuclear factor-kappa b activation in silica-induced interleukin 8 production by human bronchial epithelial cells.

Recent studies indicate that interleukin 8 (IL-8) plays an important role in interstitial lung diseases including silica-induced lung inflammation. To investigate the regulation of IL-8 expression and production in human bronchial epithelial cells, we examined the effects of silica on NF-kappaB activation. Human bronchial epithelial cell line BET-1A was cultured with hormonally defined Ham's F12 medium. The administration of silica induced IL-8 production in BET-1A dose-dependently and time-dependently. Northern blot analysis demonstrated that silica upregulated IL-8 expression in BET-1A. Moreover, electrophoretic mobility shift assays revealed that NF-kappaB activation occurred in the presence of silica, which was inhibited by antioxidants such as N-acetylcysteine (NAC). These data suggest that reactive oxygen species may be involved in the activation of NF-kappaB induced by silica.

Analysis of Variance↗