Biomedical subjects

V Vallyathan

Publications and source records attributed to V Vallyathan.

At least 91 records · Page 5Linked to original sources

PubMed1993

Binding of the cationic dye, Janus green B, as a measure of the specific surface area of crystalline silica in aqueous suspension.

Twelve preparations of crystalline silica, with a wide range of particle sizes, were assayed by a new method, which measures surface adsorption of the cationic dye Janus green B to crystalline silica samples in a buffered aqueous suspension. The same samples were also assayed for total surface area by the Brunauer-Emmett-Teller (BET) method of surface adsorption of nitrogen gas. A strong linear correlation was found between the two methods of measurement (r = 0.977). Reproducible specific surface area measurements by the Janus green B adsorption method were made on 2-mg samples using ordinary visible wave-length spectrophotometric equipment, whereas the BET method necessitated sample sizes in excess of 100 mg and more specialized instrumentation. Five size-fractionated preparations from the same Min-U-Sil alpha-quartz sample showed an increase in BET surface area and Janus green B binding per unit weight with decreasing particle size. Among four standard alpha-quartz samples tested, Min-U-Sil 5 and F600 had the lowest specific surface areas, whereas DQ-12 and Chinese standard alpha-quartz had much higher surface areas. The synthetic silica preparations cristobalite and tridymite had intermediate surface areas. Binding by the cationic dye Janus green B is consistent with a surface charge mechanism and provides a useful new technique for the assessment of surface characteristics of crystalline silica samples. Its linear relationship to surface area suggests that the ratio of aqueous surface charge to surface area is constant for different crystalline silica preparations. Comparison of surface areas for different preparations of crystalline silica is important in understanding the relative activities of these preparations in studies on mechanisms of silicosis and silica-induced lung cancer.

Azo Compounds↗

PubMed1993

Exposure of rats to hyperoxia: alteration of lavagate parameters and macrophage function.

Exposure of rats to hyperoxia (100% oxygen for 64 h) resulted in striking alterations in the properties of samples obtained by bronchoalveolar lavage. The yield of neutrophils, lymphocytes, and red blood cells was increased, while the number of harvested alveolar macrophages decreased. The acellular lavage fluid level of protein was elevated, indicating lung damage. However, acellular phospholipid levels were unchanged. The ability of alveolar macrophages to produce reactive forms of oxygen in response to zymosan was significantly decreased by oxygen exposure. This impaired function was not fully explained by a decrease in viability of these phagocytes. In contrast, stimulant-induced chemiluminescence was elevated after hyperoxia. This rise was not due to a change in cellular antioxidant levels or to a discernible increase in arachidonic acid metabolites. However, it was associated with increased cellular lipid peroxidation.

Animals↗

PubMed1992

Contrasting respirable quartz and kaolin retention of lecithin surfactant and expression of membranolytic activity following phospholipase A2 digestion.

Respirable-sized quartz, a well-established fibrogenic mineral dust, is compared with kaolin in erythrocyte hemolysis assays after treatment with saline dispersion of dipalmitoyl phosphatidylcholine, a primary phospholipid component of pulmonary surfactant. Both dusts are rendered inactive after treatment, but the membranolytic activity is partly to fully restored after treatment with phospholipase A2, an enzyme normally associated with cellular plasma membranes and lysosomes. Phospholipid-coated dusts were incubated for periods of 2-72 h at a series of applied enzyme concentrations, and the adsorbed lipid species and hemolytic activity were quantitated at each time for both dusts. Surfactant was lost more readily from quartz than from kaolin, with consequent more rapid restoration of mineral surface hemolytic activity for quartz. Interactions of surfactant and mineral surface functional groups responsible for the mineral-specific rate differences, and implications for determining the mineral surface bioavailability of silica and silicate dusts, are discussed.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1992

Enhanced generation of free radicals from phagocytes induced by mineral dusts.

Several studies have suggested that pulmonary toxicity to asbestos and silica may be mediated through oxidant-induced cell injury. We have reported recently that surface radicals associated with freshly fractured silica may be an important factor in cell injury and induction of pulmonary disease. Although the generation of oxygenated radicals in dust-cell interactions has been demonstrated, there are no data correlating the toxicity of a dust with the level of oxygen radical generation by the dust during its interaction with phagocytic cells. In the present study, we have investigated the in vitro generation of oxygen free radicals from human neutrophils and rat alveolar macrophages stimulated with freshly fractured silica, aged silica, amosite, crocidolite, chrysotile, and nontoxic dust, barite. Electron spin resonance (ESR) with the aid of a spin trap phenyl-N-tert-butyl nitrone (PBN) was used to measure the oxygen radicals generated during phagocytosis of the dusts. The relative toxicity index and ESR peak heights, on an equal surface area basis and normalized to barite as one, showed a direct relationship. The normalized toxicity indices and peak heights were: silica, 3.5 versus 2; chrysotile, 4 versus 2; crocidolite, 11 versus 8; and amosite, 26 versus 13. Addition of hydroxyl radical scavengers such as catalase, dimethyl sulfoxide, 1,3 dimethyl-2-thiourea (DMTU), sodium benzoate, and mannitol prevented the radical generation. Carmustine, a glutathione reductase-glutathione peroxidase inhibitor, caused a 5-fold increase in the radical generation. These results indicate that a nontoxic dust such as barite generates toxic oxygen radicals at a minimal level that can be quenched by the normal cellular defense system. For toxic dusts such as silica, amosite, chrysotile, and crocidolite, the potential for oxygen radical generation is enhanced by their surface properties, physical dimensions, and the surface-based radical-generating redox sites. The enhanced radical generation may impair the cellular defense system, resulting in cell injury. Use of scavengers, chelators, and potentiating agents suggests the membrane-based oxidase system as the probable primary source of the radical-generating system. The data presented herein suggest the generation of oxygen free radicals as an important primary event in silica- as well as asbestos-induced cell injury.

Animals↗

PubMed1991

One-electron reduction of carcinogen chromate by microsomes, mitochondria, and Escherichia coli: identification of Cr(V) and .OH radical.

Earlier studies have shown that a long-lived Cr(V) species is produced during the reduction of chromate (Cr(VI] by microsomes/NADPH, mitochondria, and other cellular constituents and that this Cr(V) species plays a significant role in the mechanism of Cr(VI) toxicity. The present work indicates that this species is a Cr(V) complex involving the diol moieties of NADPH as the ligand. Additionally, ESR spin trapping investigations show that the hydroxyl (.OH) radical is also generated in the reduction process. Hydrogen peroxide (H2O2) enhances the .OH generation but suppresses the Cr(V)-NADPH complex formation. Catalase decreases the .OH radical generation and enhances the Cr(V)-NADPH formation. Measurements under anaerobic atmosphere show decreased .OH radical generation, indicating that during the cellular Cr(VI) reduction process molecular oxygen is reduced to H2O2, which reacts with the Cr(V)-NADPH complex to generate the .OH radical via a Fenton-like mechanism.

Animals↗

PubMed1991

Response of alveolar macrophages to in vitro exposure to freshly fractured versus aged silica dust: the ability of Prosil 28, an organosilane material, to coat silica and reduce its biological reactivity.

We have reported previously that crushing or grinding crystalline silica results in the generation of silica-based radicals on the particulate surface and that these radicals can generate hydroxyl radicals in aqueous solution. Data in the present study indicate that freshly ground silica is more cytotoxic and is a more potent activator of alveolar macrophages than comparably sized aged silica. That is, compared to aged silica, fresh silica is 4.2-fold more potent in decreasing the membrane integrity of macrophages; is 50% more potent in activating hydrogen peroxide secretion by macrophages; and is 4.6-fold more potent in stimulating cellular chemiluminescence. Prosil 28, an organosilane material, is an effective coating agent for fresh silica. It decreases the cytotoxicity of fresh silica by as much as 78% and decreases the ability of fresh silica to induce chemiluminescence from alveolar macrophages by 58%. The data suggest that surface radicals associated with freshly cleaved dust may be an important factor in the induction of pulmonary disease. Furthermore, treating dust with coating agents may substantially decrease toxicity.

Animals↗

PubMed1991

Bronchiolar inflammation and fibrosis associated with smoking. A morphologic cross-sectional population analysis.

The lungs of 42 smokers and 13 nonsmoking males of various ages who died suddenly and unexpectedly were examined grossly using Gough-Wentworth whole-lung sections and by microscopic planimetry to assess the severity and prevalence of emphysema. The bronchioles in representative histologic sections were evaluated for inflammation and epithelial metaplasia as well as for fibrosis and muscular hypertrophy. Postmortem interviews with next of kin established a history of cigarette smoking and excluded possible occupational exposures to toxic or particulate inhalants. Emphysematous changes were not prominent in members of the study group, but they tended to be more severe in smokers (p = 0.059) and increased in severity with age (p less than 0.001). Inflammatory changes (so-called smoker's bronchiolitis) were evident in smokers of all ages, although they were significantly less prominent in the lungs of older smokers. On the other hand, respiratory and membranous bronchiolar wall fibrosis was increasingly evident in older smokers (p less than 0.05). Muscular hypertrophy in the bronchiolar walls was significantly greater in smokers, but a change with age was not observed. These findings strongly suggest that bronchiolar fibrosis is associated with chronic cigarette use. These lesions occur independently of emphysema and may account for some of the subtle physiologic alterations observed in smokers.

Adolescent↗

PubMed1990

Role of free radicals in the mechanisms of hemolysis and lipid peroxidation by silica: comparative ESR and cytotoxicity studies.

Electron spin resonance (ESR) and cytotoxicity measurements were made on newly fractured silica to examine specifically the role of the fracture-induced, silicon-based radicals (Si. and SiO.) and silica-generated hydroxyl (.OH) radicals in the mechanism of the cell membrane damage by silica. The concentration of the Si. and SiO. radicals was controlled through decay processes, thermal annealing, and boiling, while that of the .OH radicals was varied by using catalase, superoxide dismutase, KMnO4, Na2SeO3, ascorbic acid, and metal ions, and monitored via ESR spectroscopy. The dust's cytotoxicity potential was evaluated by measuring the silica-induced hemolysis and also by determining lipid peroxidation (using linoleic acid). From the comparison of hemolysis and ESR results it is deduced that the radicals play little or no role in the silica-induced hemolysis. However, the lipid peroxidation data indicate that the radicals might be involved in the initiation of an oxidative chain reaction leading to the macrophage membrane damage through lipid peroxidation.

Animals↗

PubMed1990

ESR spin trapping and cytotoxicity investigations of freshly fractured quartz: mechanism of acute silicosis.

Electron spin resonance (ESR) measurements show that grinding of quartz particles in air produces silicon-based (Si. and SiO.) radicals which decay with aging in air. ESR spin trapping measurements provide evidence for the generation of hydroxyl and possibly superoxide radicals from a suspension of fresh quartz particles. The hydroxyl radical generation potential of the fresh quartz particles decreases on storing in ambient air and on the addition of catalase, superoxide dismutase, desferroxamine, or DMSO. Silica-induced lipid peroxidation also decreases on storing the fresh particles in ambient air. These findings suggest that oxygenated radicals play a role in the biochemical mechanism of pneumoconiosis in general and acute silicosis in particular.

Acute Disease↗

PubMed1990

Pulmonary arteriolar muscularization in coal workers' pneumoconiosis and its correlation with right ventricular hypertrophy.

The relationship between the thickness of the walls of small pulmonary arteries (the medial wall thickness as a percentage of external diameter, percentage of medial thickness) in coal miners and control subjects were studied using morphometric techniques and correlated with the degree of right ventricular hypertrophy, severity of coal workers' pneumoconiosis, emphysema, and other chronic lung diseases. Pulmonary arteries less than 100 microns in external diameter were identified and the external diameter, medial thickness, and intimal thickness were quantitatively measured in the lung tissues of 57 coal miners and 15 control subjects with and without other chronic lung diseases. Coal workers' pneumoconiosis, emphysema, and right ventricular hypertrophy were assessed uniformly in all cases. The arterial wall thickness correlated with right ventricular hypertrophy, progressive massive fibrosis, and other chronic lung diseases. Severity of emphysema also showed a weak correlation. Although the functional significance of these findings is not known, we conclude that the muscularization of pulmonary arterioles provides a structural basis for the development of right ventricular hypertrophy in coal miners.

Adult↗

PubMed1989

The chemical properties of silica particle surface in relation to silica-cell interactions.

Although silicosis has been studied extensively, the mechanism is still not fully understood. Experiments do provide evidence that the actions of unique properties of silica surface on the cell membrane are the starting point of silicotic processes. This paper summarizes literature on chemical properties of silica surface, and the effect of particle size on silica toxicity. This paper also discusses the ways in which silica dusts are thought to interact with the cell membrane, with emphasis on freshness, hydrogen bonding, and free-radical interactions.

Animals↗

PubMed1989

Detection of reactive free radicals in fresh coal mine dust and their implication for pulmonary injury.

Freshly ground and aged anthracite and bituminous coal samples were investigated by electron spin resonance (ESR) spectroscopy to detect the presence, concentration and reactivity of free radicals. Freshly ground anthracite coal produced greater concentration of free radicals than the bituminous coal, and the radical reactivity was also greater for the anthracite. The reactivity of the newly produced free radicals in the anthracite dust correlated with the dust's toxicity. Furthermore, similar coal-based free radicals were detected in the lung tissue of autopsied coal miners, suggestive of persistent reactivity by the embedded coal dust leading to the progressive disease process. Results of the studies on the severity of coal workers' pneumoconiosis (CWP) and free radical concentration in lung tissue support this hypothesis.

Coal↗

PubMed1988

ESR evidence for the hydroxyl radical formation in aqueous suspension of quartz particles and its possible significance to lipid peroxidation in silicosis.

Electron spin resonance (ESR) spectrum of the hydroxyl (.OH) radical spin adduct with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide has been obtained in suspensions of freshly ground quartz particles. The concentration of the spin adduct (and hence of the .OH radicals) increases with the amount of grinding. The dust's potential for the generation of the .OH radicals is maximum when fresh (i.e., immediately after grinding) and decreases to 50% in about a day on storage in air. Studies involving metal chelates indicate that the .OH radical formation involves mainly the silica surface and H2O rather than the Fenton reaction. The results suggest that hydroxyl radical reaction(s) could be important in the lipid peroxidation and fibrogenicity by quartz dust, particularly in acute silicosis.

Electron Spin Resonance Spectroscopy↗

PubMed1988

Pneumoconiosis in carbon electrode workers.

Pneumoconiosis was diagnosed in five workers involved in the manufacture of carbon electrodes. Possible etiologies are discussed. It is generally believed that pneumoconiosis ceased to be a problem in this industry after World War II; however, the reported cases all resulted from exposures after 1940. These findings question the efficacy of recent and current engineering controls and suggest the need for further study of this industry.

Carbon↗

PubMed1988

Generation of free radicals from freshly fractured silica dust. Potential role in acute silica-induced lung injury.

Data presented here indicate that freshly fractured silica exhibits surface characteristics and biologic reactivity distinct from aged silica, and on this basis we propose that these surface features may lead to enhanced manifestations of lung injury. Grinding of silica produces approximately 10(18) Si and Si-O (silicon-based) radicals per gram of dust on the particulate surface which are characterized by an electron spin resonance (ESR) spectrum centered around g = 2.0015. These silicon-based radicals react with aqueous media to produce OH radicals, which are demonstrable using a DMPO spin trap. The concentration of silicon-based radicals in silica decreases with aging in air and exhibits a half-life of approximately 30 h, whereas its ability to generate OH radicals in aqueous solution decreases with a half-life of approximately 20 h. However, on storage in aqueous media, the concentration of silicon-based radicals and the dust's ability to generate OH radicals decrease significantly within a few minutes. Freshly ground silica is also more biologically reactive than aged silica, because freshly crushed silica activates a greater respiratory burst in alveolar macrophages than aged silica, i.e., storage of ground dust in air decreases silica-induced superoxide anion secretion, hydrogen peroxide release, and NBT reduction by 25%, 68%, and 43%, respectively. Furthermore, compared to aged silica, freshly ground silica exhibits a greater cytotoxic effect on cellular membrane integrity, i.e., a 1.5-fold increase in LDH release from macrophages, a 36-fold increase in hemolytic activity, and a three-fold increase in the ability to induce lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1986

In vitro biologic responses to native and surface-modified asbestos.

A comparative study was made of in vitro biologic responses to native chrysotile, amosite, and crocidolite and corresponding asbestos fibers whose surfaces were modified by metal oxides. Interferon induction by influenza virus was depressed by approximately 50% by all native asbestos whereas corresponding surface modified asbestos minimally affected this nonspecific cellular defense mechanism. The release of the cytoplasmic enzyme, lactate dehydrogenase (LDH), and lysosomal enzymes, beta-N-acetylglucosaminidase (beta-NAG) and beta-glucuronidase (beta-Gluc), by rat alveolar macrophages after exposure to either native or surface-modified asbestos (which is indicative of membrane damage) was monitored. Although both native and surface-modified asbestos induced significant leakage of LDH, generally, lesser amounts of the enzyme were released as a result of exposure to the latter than to native asbestos. Whereas all forms of native asbestos caused significant release of beta-NAG and beta-Gluc, leakage of these enzymes from macrophages exposed to surface-modified asbestos was minimal. In contrast to native asbestos which induced irritation of cell membranes, as indicated by hemolysis of sheep erythrocytes, surface-modified asbestos exhibited minimal hemolytic activity. The findings indicate that surface modification of different asbestos by metal oxides generally lessened the adverse effect of the native mineral on the aforementioned biologic entities.

Animals↗

PubMed1986

Effect of diesel emissions and coal dust inhalation on heart and pulmonary arteries of rats.

Fischer 344 (SPF) rats were exposed by inhalation to respirable particulate levels of 2 mg/m3 diesel emissions, diesel emissions plus coal dust, coal dust, or air for 7 h/d, 5 d/wk for 24 mo. The effects of treatment on body and heart weights, right and left ventricular wall thickness, severity of cardiomyopathy, and changes in the small pulmonary arteries were evaluated after 24 mo of exposure. In all dust-exposed animals, light microscopic examination of the lungs revealed dust-laden macrophages in alveolar spaces and focal accumulations of dust-laden macrophages near the respiratory bronchioles associated with hyperplasia of type II cells. This response was more prominent in animals exposed to diesel emissions alone. Age-related myocardial fibrosis and inflammatory infiltrates were common in all four groups. No statistically significant differences were detected between the groups for heart weights, ventricular wall thickness, and pulmonary arterial wall thickness. However, animals exposed to diesel emissions did show a consistent trend toward increased pulmonary arterial wall thickness, for all size categories of artery, compared to controls.

Animals↗

PubMed1985

The role of analytical techniques in the diagnosis of asbestos-associated disease.

There is increasing concern over the adverse health effects resulting from asbestos exposure. The mineralogy of asbestos and the pathology of asbestos-associated diseases is briefly reviewed. Techniques for tissue sampling, histopathological diagnostic criteria and the role of light microscopy (LM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and X-ray diffractometry (XRD)--in the identification and quantitation of asbestos bodies and fibers in the lung tissue samples--are discussed. The value of a systematic quantitative approach is emphasized in order to differentiate the dose relationships and disease patterns.

Asbestos↗