Pneumoconioses are characterized as irreversible, progressive respiratory diseases. No effective therapy exists to prevent progression of these diseases. Whole-lung lavage (WLL) might limit the rate of disease progression through the removal of dust, inflammatory cells, and cytokines. We performed WLL on a 54-year-old underground miner employed as a motorman and roof bolter and a 55-year-old driller at a surface coal mine. Both demonstrated normal lung function and chest radiographs showing ILO profusion category 2 nodular interstitial changes. From Subject 1, we recovered 5.24 x 10(8) cells (90% macrophages) from the right lung and 3.45 x 10(8) cells (94% macrophages) from the left lung. WLL removed 1.82 g of mineral dust (non-coal) on the right and 1.64 g on the left. From Subject 2, we recovered 7.49 x 10(8) cells (46% macrophages) from the right and 9.78 x 10(8) cells (69% macrophages) from the left lung. WLL removed 0.40 g of mineral dust on the right and 0.53 g on the left. Proinflammatory cytokines, growth factors, and cellular enzymes were also recovered. In cases of pneumoconiosis, WLL is capable of removing relatively large quantities of dust, cells, and soluble materials from the lungs. Only long-term follow-ups of individuals with progressive dust-induced disease who receive WLL therapy in the context of a clinical trial will provide information regarding the importance of removing mineral dust and inflammatory cells from the lung.
Although diesel exhaust particles (DEP) are known to produce pulmonary disorders, the xenobiotic metabolic pathways associated with DEP detoxification and bioactivation remain unclear. In this study, the effect of acute exposure of DEP on phase I and phase II enzymes of rat lung was investigated. Intratracheal administration of DEP produced an induction of cytochrome P-450 (CYP) 1A1 enzyme protein and activity at 1 d postexposure, with the enzyme level returning to control at 5 d postexposure. On the other hand, carbon black (CB), a particle control, did not show any induction of CYP1A1 protein or enzyme activity. However, both DEP and CB significantly decreased CYP2B1 protein and enzyme activity at 1 d postexposure. The decrease in CYP2B1 enzyme protein and activity by DEP or CB treatment was observed up to 7 d postexposure. DEP and CB treatments also significantly attenuated glutathione S-transferase (GST)-pi protein at 1 d postexposure. Both DEP and CB at 35 mg/kg significantly decreased the activities of GST and catalase at 1 and 7 d postexposure. DEP, but not CB, significantly induced quinone reductase (QR) activity at 7 d postexposure. This study suggests that DEP may induce CYP1A1 and QR enzymes via a chemical effect, while the carbonaceous core may be involved in the attenuation of CYP2B1, GST, and catalase proteins and enzyme activities.
A solvent partition technique for the microencapsulation of hydrocortisone-polylactic acid has been developed for the preparation of microcapsules of controlled particle size distribution and drug loading. The method involves continuous injection of a drug-polymer solution with a syringe infusion pump into flowing mineral oil where microcapsules are formed as the solvent of the drug-polymer is partitioned into the mineral oil. Using preselected syringe needle size and mechanical control of the mineral oil flow rate at the needle tip, microcapsules of consistent particle sizes and desired drug loadings were prepared. Microcapsules of different internal structures were also prepared by varying the solvent system for the drug-polymer preparation. Dissolution studies showed that at the same drug loading, the rate of the percentage drug release increased with decreasing particle size, and that at similar particle size distributions, the rate increased with increasing drug loading. These results indicate that both the particle size distribution, and the drug loading must be controlled in a microencapsulation process to produce microcapsules of controlled drug release rate.
An emulsion method was developed for the incorporation of water-soluble mitomycin C into polylactic acid biodegradable microcapsules. With an average particle size of about 95 microns, microcapsules with a desired loading of from 3.65 to 13.80 per cent were prepared. These microcapsules, which contained both crystalline and finely dispersed drug particles, showed a dose-dependent drug release pattern with microcapsules of higher drug loading having a faster release rate than those of lower drug loading. Effective sterilization of the microcapsules for parenteral use was achieved by 60Co gamma-ray irradiation, which did not affect the microcapsule structure, release rate or drug stability. Mitomycin C showed dose-dependent antiproliferative activity against the growth of the K562 human erythroleukaemia cells. The microencapsulated dosage form of mitomycin C was found to enhance the drug's activity through sustained drug release. In experiments where drug concentrations in the cell medium were reduced according to the drug's biological half-life, the microcapsule systems showed a distinct advantage over the non-capsulated dose for the kinetic inhibition of K562 cell growth.
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