Daniel E. Banks

Assessment of the relationship between isocyanate exposure levels and occupational asthma.

As part of a previous study, we identified Ontario cases of isocyanate-induced occupational asthma (OA) and the companies at which they worked. The Ontario Ministry of Labour maintained a computerized database including isocyanate air sampling determinations conducted by the Ministry. Within this database, we compared levels of isocyanate concentrations measured at 20 case companies [with compensated isocyanate asthma (OA) claims] with 203 noncase companies, based on air samples collected during the same 4-year period during which the OA claims arose. The proportion of case companies that were ever recorded as having a measured ambient isocyanate concentration of > or = 0.005 ppm was greater than that for noncase companies, for TDI users (43% vs 22%), and for MDI users (40% vs 27%). This reached conventional significance when combined across companies and isocyanate types (50% vs 25%; P < 0.05). This provides some evidence that facilities having OA claims have higher isocyanate exposures than do those without claims.

Inhibitory action of tetrandrine on macrophage production of interleukin-1 (IL-1)-like activity and thymocyte proliferation.

Tetrandrine is a bisbenzylisoquinoline alkaloid which has been shown to exhibit antifibrotic activity against silicosis. Tetrandrine is characterized by its strong binding to alveolar macrophages and inhibition of particle-induced respiratory burst activity in these phagocytes. In contrast, tubocurine and tubocurarine are structurally similar to tetrandrine but exhibit little effect on fibrosis or activation of alveolar macrophages. The objective of the present study was to test the effect of tetrandrine on macrophage production of monokines in response to occupational dusts, and to determine tetrandrines effect on monokine-medicated cell growth using a mouse thymocyte proliferation assay and lipopolysaccharide (LPS) as a positive control. Stimulation of alveolar macrophages by respirable silica dust resulted in a release of monokines which caused a fourfold increase in thymocyte proliferation. Coal dust, on the other hand, had no effect on macrophage production of this cytokine. Tetrandrine was found to exhibit a dose-dependent inhibition of monokine release from both silica and LPS-stimulated alveolar macrophages. In experiments where thymocytes were directly treated with tetrandrine, a dose-dependent inhibition of thymocyte proliferation was noted with both interleukin-1-(IL-1) specific and nonspecific mitogenic (concanavalin A) actions. In contrast to the inhibitory potency of tetrandrine, tubocurarine was found to have no effect on either the production of monokines by LPS-stimulated alveolar macrophages or IL-1-mediated thymocyte proliferation. These results provide a correlation between the antifibrotic effect of tetrandrine and inhibition of macrophage activation.

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.

Multiple Emulsion-Mediated Enhancement of the Therapeutic Effect of Tetrandrine against Silicosis

Abstract Using a water-in-oil-in-water multiple emulsion system developed for pulmonary drug targeting, the effectiveness of tetrandrine as an antifibrotic agent and the therapeutic advantage of a tetrandrine emulsion over drug in solution for the treatment of silicosis were investigated in rats. Previously we have shown that the action of tetrandrine is attributed to its ability to inhibit the release of reactive oxygen metabolites and inflammatory cytokines by alveolar macrophages, and that targeted delivery of tetrandrine to alveolar macrophages using a multiple emulsion system minimizes drug toxicity, maintaines the drugs pharmacological activity, and enhances tetrandrine distribution in the lungs while reducing systemic drug distribution. The purpose of the present study is to provide in vivo evidence of emulsion-mediated enhancement of drug action in the lungs against silica-induced lung injury using a rat model. The antifibrotic action of tetrandrine was evaluated by examinations of lung histology...

Understanding circulatory shock. Is it hypovolemic, cardiogenic, or vasogenic?

Circulatory shock comprises a group of complex circulatory syndromes that result from a variety of conditions. It alters the function of most organ systems and has very high mortality. Identification of the type of shock (hypovolemic, cardiogenic, vasogenic, or a combination) and optimal treatment are aided by hemodynamic monitoring, including determination of preload, cardiac output, and systemic vascular resistance. Experimental studies and isolation of bioactive substances have improved understanding of the mechanisms involved in shock. Restoration of intravascular volume, cardiac contractility, and vascular tone and control of the underlying septic process when applicable are the basis of current therapy. Close monitoring and support of the affected organ systems in an intensive care environment facilitate recovery. Encouraging results with new treatments indicate improved chances for a satisfactory outcome in patients with circulatory shock.