silicon and Pulmonary-Fibrosis

Interstitial pneumonia (IP) is a collective term for diseases whose main lesion is fibrosis of the pulmonary interstitium, and the prognosis associated with acute exacerbation of these conditions is often poor. Therapeutic agents are limited to steroids, immunosuppressants, and antifibrotic drugs, which and have many side effects; therefore, the development of new therapeutic agents is required. Because oxidative stress contributes to lung fibrosis in IP, optimal antioxidants may be effective for the treatment of IP. Silicon (Si)-based agents, when administered orally, can continuously generate a large amount of antioxidant hydrogen in the intestinal tract. In this study, we investigated the effect of our Si-based agent on methotrexate-induced IP, using the IP mouse models. Pathological analysis revealed that interstitial hypertrophy was more significantly alleviated in the Si-based agent-treated group than in the untreated group (decreased by about 22%; P < 0.01). Moreover, additional morphological analysis demonstrated that infiltration of immune cells and fibrosis in the lungs were significantly inhibited by treatment with the Si-based agent. Furthermore, Si-based agent reduced oxidative stress associated with IP by increasing blood antioxidant activity. (increased by about 43%; P < 0.001). Taken together, these results suggest that Si-based agents can be effective therapeutic agents for IP.

Topics: Animals; Lung; Lung Diseases, Interstitial; Mice; Prognosis; Pulmonary Fibrosis; Silicon

Determine whether surface dust grab samples taken from a large military base in Iraq are toxic and respirable.. X-ray diffraction for mineral content, x-ray fluorescence for elemental content, in vivo mouse dust challenges for assessment of histological changes, bronchoalveolar lavage for cytokines, polarizing light microscopy for crystals in lung tissue, and Fluorescence Activated Cell Sorting for cell surface and intracellular markers were utilized.. Camp Victory, Iraq dust taken during wartime contains respirable particles 2.5 microns in size, constituting particulate matter air pollution. Dust particles are angular and have sharp edges. Trace metals (including titanium) calcium and silicon are present. Mice with airway instillation of dust have polarizable crystals in lung and septate inflammation. Regulatory T cells (CD4⁺CD25⁺FOXP3⁺) are decreased in thymus and spleen. Interleukin-2 (IL-2) is upregulated in bronchoalveolar lavage.. Respirable Iraq dust leads to lung inflammation in mice similar to that seen in patients with polarizable crystals, which seem to be titanium.

Topics: Animals; Birefringence; Bronchoalveolar Lavage Fluid; Calcium; Dust; Inhalation Exposure; Interleukin-2; Iraq; Lymphocyte Count; Male; Mice; Mice, Inbred C57BL; Military Facilities; Particulate Matter; Pneumonia; Pulmonary Fibrosis; Silicon; Spleen; T-Lymphocytes, Regulatory; Thymus Gland; Titanium; Up-Regulation

To further study the pathogenic mechanism of crocidolite, the imperceptible changes of crocidolite surface in rat were observed.. The animal model was established and the changes in the rat infected with dust were observed by use of microscopy, SEM, differential thermal analysis and IR spectroscopy.. In the course of interaction between organism protein and crocidolite, the protein symmetry decreased and structure loosened. The silicon of crocidolite was bonded with the alkyl, amido- of protein. New absorption bands of Si-O-C(N), Si-R clearly appeared. The organism cleared the dust by means of dissolution, enwrapping, winding or in the way of biochemical dissolution, and the fibre became shortened, broken, bifurcated, ends-rounded, and also it could dissolve, transfer and chemically react on surface.. The results showed that the surface radicals of asbestos fibre reacted with some albumen in tissue and hence formed new surface mediator. It is a new form of dissolution and reaction of fibre in vivo that fibres in alveoli transform to carbonate. The residual substances of crocidolite are mainly Si-O. Tissue membrane is the retardation cingulum of dust transference in vivo.

Topics: Animals; Asbestos, Crocidolite; Asbestosis; Dust; Microscopy, Electron, Scanning; Mineral Fibers; Pleural Diseases; Pulmonary Fibrosis; Rats; Silicon

To evaluate the possibility of quantifying alveolar dust burden in conditions of exposure to silica, four groups of subjects were submitted to bronchoalveolar lavage (BAL): 10 healthy control subjects and 39 patients affected by diffuse interstitial lung disease (DILD) never exposed to dust, 23 silicotic patients and 12 chronic bronchitis patients with a history of occupational exposure to silica dust. Five to ten million BAL recovered cells were analysed with an energy-dispersive X-ray microanalysis (EDXA) system to determine the silicon content, expressed in a semi-quantitative way as silicon to sulphur (Si/S) ratio. The results were independent of smoking habit. The Si/S median values (interquartile range in brackets) for the four groups were 0.53 (0.5-0.65), 0.60 (0.41-0.8), 1.23 (1.06-1.39), 1.31 (1.11-1.97), respectively. Silicotics and simply exposed individuals did not show a significant discrepancy, but they were both significantly different in comparison with normal and DILD patients without history of exposure (p less than 0.001). 14.3% false negative cases were found, and 4.1% false positive cases (none among normal subjects). We did not see any significant relationships between the amount of silicon and the duration of exposure or the degree of chest X-ray involvement. A study of cytocentrifuge slides from the same subjects by polarizing light microscopy revealed a lower sensitivity (34% false negative cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bronchitis; Bronchoalveolar Lavage Fluid; Electron Probe Microanalysis; Female; Humans; Male; Microscopy, Polarization; Middle Aged; Occupational Exposure; Pulmonary Fibrosis; Silicon; Silicosis; Smoking; Time Factors

The inflammatory and fibrogenic potential of three naturally occurring and two man-made industrial minerals were compared. Groups of five rats each received respectively a single intratracheal instillation of saline (control), UICC chrysotile B asbestos, short chrysotile 4T30, attapulgite, xonotlite (a calcium silicate), and Fiberfrax (an aluminum silicate) at doses of 1, 5, and 10 mg. One month after the treatment, assessment of lung morphology and bronchoalveolar lavage were performed on each animal. Under these conditions, UICC chrysotile B at all doses tested (1, 5, and 10 mg) induced fibrotic lesions in bronchiolar tissues while short chrysotile 4T30 (1, 5, and 10 mg) caused focal accumulation of inflammatory cells in the alveolar structures but no apparent fibrosis. Compared to these positive reactions with different fibrogenicity, xonotlite caused minimal inflammatory reactions detectable only at high dose (10 mg) and by bronchoalveolar analysis. By contrast, the rat lung reacted more significantly to attapulgite and Fiberfrax although the tissue reaction differed considerably for these two materials. While attapulgite, at doses up to 10 mg caused minimal reactions characterized by mononuclear cell infiltration mainly in the alveolar structures, Fiberfrax at 1 mg and higher caused significant granulomatous reactions and the appearance of early fibrosis. Overall the order of lung biological reactivity observed for the various silicates was xonotlite much less than attapulgite less than short chrysotile 4T30 less than Fiberfrax less than UICC chrysotile B. These observations indicate that Fiberfrax, attapulgite, and, to a lesser extent, xonotlite are biologically active within the time span studied and potentially deleterious for lung tissue.

Topics: Animals; Asbestos; Asbestos, Serpentine; Bronchoalveolar Lavage Fluid; Calcium Compounds; Dose-Response Relationship, Drug; Lung; Magnesium; Magnesium Compounds; Male; Pulmonary Fibrosis; Rats; Rats, Inbred Strains; Silicates; Silicic Acid; Silicon; Silicon Compounds; Silicon Dioxide; Specific Pathogen-Free Organisms; Time Factors

Histological examination on lung tissue obtained from 10 symptomatic welders was performed by two certified pathologists without the knowledge of the patients' clinical condition. In all cases, there was some degree of interstitial fibrosis; in five the degree of fibrosis was considered to be moderate to pronounced. The tissue was also analysed by energy dispersive x ray analysis and elemental contents were compared with age matched controls. There was a large amount of iron in the lungs of welders but the silicon content did not differ from the control subjects. No specific foreign element was detected. It is concluded that (1) interstitial pulmonary fibrosis is seen in some welders and (2) the cause of fibrosis does not appear to be coexisting silicosis.

Topics: Adult; Electron Probe Microanalysis; Humans; Iron; Lung; Male; Middle Aged; Pneumoconiosis; Pulmonary Fibrosis; Silicon; Welding

As the preliminary results of experimental studies on dust from the palygorskite group have led to some confusion a detailed description of the completed investigation is given for clarification. As in other experiments the biological effects have been shown to be associated with the physical characteristics of the fibres in these specimens. Samples of sepiolite and attapulgite from Spain and a single sample of palygorskite from the United Kingdom have been studied. Serious abnormalities were produced only by the palygorskite and one of the attapulgite dusts. The palygorskite is of no commercial interest and the attapulgite was from one small deposit and was used only in the preparation of drilling mud in the exploration of oil deposits.

Topics: Administration, Inhalation; Animals; Dust; Female; Magnesium; Magnesium Compounds; Magnesium Silicates; Male; Mesothelioma; Microscopy, Electron; Minerals; Pleural Neoplasms; Pulmonary Fibrosis; Rats; Rats, Inbred F344; Rats, Inbred Strains; Silicon; Silicon Compounds

Biopsies from 68 patients suffering from interstitial lung disease were examined with regard to minerals using Energy Dispersive X-Ray Analysis (EDXA). In 31 patients a higher portion of minerals or elements were found as pigments. The interpretation of these findings is difficult. If there is a professional exposition and a reaction of the lung parenchyma the findings could be of clinical value.

Topics: Aluminum; Biopsy; Electron Probe Microanalysis; Humans; Iron; Lung; Minerals; Pulmonary Fibrosis; Silicon

Current methods for determining the fibrogenicity of substances are based on relatively long term exposures of animals to the substance and the evaluation of morphological changes occurring in the lung. The use of inhalation chambers, which produce a more physiological environment, suffer from the need for particularly long exposure times (1-3 years). The present study describes a technique using scanning electron microscopy, energy dispersive analysis, and a digitiser pad with a computer to evaluate the fibrogenicity of silica in cases of known exposure. Scanning electron micrographs taken from silicotic lungs were evaluated for the degree of thickening (fibrosis) and the same areas were analysed for silicon content. Correlations between silicon content and septal thickening were shown to be significant (p less than 0.0001). The study also describes the concentrations of elements found in normal lungs. The technique for establishing correlation curves between elemental concentrations and septal thickening could be of value in determining the fibrogenicity of pure substances after short exposures in an environmental chamber.

Topics: Aluminum; Electron Probe Microanalysis; Elements; Humans; Lung; Magnesium; Microscopy, Electron, Scanning; Pulmonary Fibrosis; Reference Values; Silicon; Silicosis

Pulmonary specimens obtained from ten normal subjects and 53 patients with various pulmonary diseases were studied with energy-dispersive x-ray analysis. The amount of silicon in the pulmonary tissue was determined and expressed as a silicon/sulfur (Si/S) ratio. This Si/S ratio was below 0.2 in the ten normal subjects and in 14 patients who had various interstitial pulmonary diseases but had no previous history of exposure to silica or other dusts known to cause pulmonary fibrosis. The Si/S ratio was greater than 0.3 in 19 of 22 patients who had a history of exposure to silica dust and had clear-cut histologic evidence of silicosis. The Si/S ratio was less than 0.2 in 12 and between 0.2 and 0.3 in two of the 14 patients who had a history of exposure to silica dusts but no clinical or histologic evidence of silicosis. We conclude that the determination of the silicon content of tissue by energy-dispersive x-ray analysis is useful in separating the fibrosis due to silicosis from the other causes of pulmonary fibrosis.

Topics: Adult; Aged; Electron Probe Microanalysis; Humans; Lung; Male; Middle Aged; Pulmonary Fibrosis; Radiography; Silicon; Silicosis; Sulfur

The elemental content of alveolar septa in various pneumoconioses was examind for a possible relationship to interstitial fibrosis. Silicon content, as well as heavy metal content, were evaluated to deterrmine possible interrelationships between the various inorganic dusts. Silicon levels were determined on the basis of silicon-sulphur ratios to accommodate for differences in tissue mass. A study of the variation of silicon-sulphur ratios in silicotics and normal individuals showed no false positives by our diagnostic criteria. A study of 11 cases of siderosis revealed that silicon was not responsible for the fibrosis as previously believed. An analysis of the lungs of 25 non-silicotic fibroses revealed that silicon-sulphur ratios were within normal limits. This technique should be useful in quantitating high exposure to certain dusts and in studying the relationship of such dusts to fibrosis.

Topics: Electron Probe Microanalysis; Humans; Macrophages; Pneumoconiosis; Pulmonary Alveoli; Pulmonary Fibrosis; Silicon; Silicosis; Sulfur

Abnormal numbers of birefringent particles have been found in the lungs of seven patients (five vineyard workers, one farmer, and one rural resident) in association with a spectrum of early to late interstitial inflammation and fibrosis. Nodular granulomas of the type seen in silicosis were absent. Scanning electron microscopy and energy dispersive x-ray analysis of 177 individual particles (less than 5 micrometer.) in situ in the lungs of four of the patients showed mostly silicates (notably aluminum, silicon, and potassium), with 5 to 10 per cent silicon dioxide. An analysis of particles less than 5 micrometer. from both vineyard and non-vineyard soil showed lung and soil particles to have a similar composition. The presence of large amounts of silicates in the lung tissues, in association with chronic inflammation and fibrosis, implicates the silicates in the causation of the fibrosis. The silicate deposits may, in large part, be a marker, reflecting a mixture of toxic soil additives or pesticides found in commercial clay silicate products or in dusts from the soil itself. The findings do not exclude lung pathology of a similar nature in regions outside of the farm.

Topics: Aged; Agricultural Workers' Diseases; Birefringence; Female; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Pulmonary Fibrosis; Silicon; Silicosis; Soil; X-Rays

Topics: Dust; Elastic Tissue; Electron Probe Microanalysis; Histocytochemistry; Humans; Lung; Macrophages; Microscopy, Electron; Minerals; Pulmonary Alveoli; Pulmonary Fibrosis; Silicon

Topics: Animals; Molybdenum; Pulmonary Fibrosis; Rats; Silicon; Titanium; Tungsten