Faculty Bibliography

Inhaled acidic sulfate aerosols affect various aspects of lung function, presumably by delivery of hydrogen ion (H+) to target sites. Recent evidence suggests that the relationship between response and H+ content of the exposure atmosphere may depend upon the specific sulfate species with which the H+ is associated. This study examined comparatively the effects of exposure to the two main ambient acidic sulfates, sulfuric acid (H2SO4) and ammonium bisulfate (NH4HSO4), using the phagocytic activity of alveolar macrophages as the endpoint. Rabbits were exposed to 250-2000 micrograms/m3 H2SO4 (as SO4(-2)) and 500-4000 micrograms/m3 NH4HSO4 (as SO4(-2)) for 1 hr/day for 5 days; bronchopulmonary lavage was then performed for recovery of free lung cells. Phagocytosis, measured by uptake of opsonized latex spheres in vitro, was altered by exposure to H2SO4 at concentrations greater than or equal to 500 micrograms/m3 and to NH4HSO4 at greater than or equal to 2000 micrograms/m3. Assessment of results in terms of the calculated hydrogen ion concentration in the exposure atmosphere showed that identical levels of H+ produced different degrees of response depending upon whether exposure was to H2SO4 or NH4HSO4. On the other hand, macrophages incubated in acidic environments in vitro responded similarly regardless of whether H2SO4 or NH4HSO4 was used to adjust the pH. Possible reasons for the difference in response observed in vivo and in vitro are discussed. Speciation of ambient acidic sulfate aerosols may be needed in atmospheric monitoring so as to assess the presence of H+ posing the greatest biologic hazard following inhalation exposure

Guinea pigs were exposed to ultrafine coal fly ash produced in a laboratory furnace. The average mass median aerodynamic diameter and the average mass concentration of Illinois no. 6 fly ash produced in all exposure conditions were 0.21 microns and 5.8 mg/m3, respectively. In guinea pigs exposed to Illinois no. 6 fly ash, total lung capacity (TLC), vital capacity (VC), and diffusing capacity for carbon monoxide (DLco) were significantly reduced below the control values immediately, 2 h, and 8 h postexposure. The diffusing capacity was still 10% below the control 96 h after exposure. The total sulfate in the Illinois no. 6 fly ash as determined using ion chromatography is 1105 +/- 120 micrograms/m3. Animals exposed to the Montana lignite fly ash at comparable concentration and particle size did not show alteration in diffusing capacity. The data suggest that part of the sulfate present in the fly ash of Illinois no. 6 could be in the form of sulfuric acid and is responsible for the adverse effects observed in the exposed animals. The sulfuric acid in the fly ash of Montana lignite is neutralized by its high alkali content and produces no change in lung functions

Based on a review of anatomical and physiological findings, we suggest that the hippocampus may be viewed as a positive feedback device (autoassociator), which is capable of modifying the activity of the neocortical neurons. We examine the three-dimensional organization of evoked and spontaneous physiological patterns of the hippocampus and suggest rules how these patterns emerge during different behaviors from a hard-wired structural network. The high spatial coherence of theta activity is due to an external pacemaker, while the high synchrony of population bursts underlying hippocampal sharp waves is explained by the similar probability of recruitment of neurons by the burst-initiator cells along the whole extent of the hippocampus. We suggest that the burst-initiator cells are a group of CA3 neurons whose excitability is increased by a transient potentiation action of the neocortical activity during theta-concurrent exploratory behaviors. We hypothesize that sharp wave-concurrent population bursts result in a highly synchronous hippocampal output, converging preferentially on those entorhinal neurons which were instrumental in the creation of the burst-initiator neurons. The feedback action of population activity thus provides a selective mechanism for potentiation of connections between information-carrying neurons in the hippocampus and entorhinal cortex. The state-dependent operations of the anatomical hardware also point to the importance and advantage of studying the physiological activity of the intact brain

Guinea pigs were exposed to ultrafine aerosols (less than 0.1 micron) of zinc oxide with a surface layer of sulfuric acid. These acid-coated aerosols are typical of primary emissions from smelters and coal combustors. Repeated daily 3-hr exposures for 5 days produce decrements in lung volumes and pulmonary diffusing capacity and elevations of lung weight/body weight ratio, protein, and number of neutrophils in pulmonary lavage fluid at concentrations of 20 micrograms/m3. A single 1-hr exposure to 20 micrograms/m3 causes increased bronchial reactivity. Higher concentrations of conventionally generated sulfuric acid mist are required to produce responses of similar magnitude

Ultrafine metal oxides and SO2 react during coal combustion or smelting operations to form primary emissions coated with an acidic SOx layer. Ongoing work in this laboratory has examined the effects of sulfur oxides on pulmonary functions of guinea pigs. We have previously reported that 20 micrograms/m3 acidic sulfur oxide as a surface layer on ultrafine ZnO particles decreases lung volumes, decreases carbon monoxide diffusing capacity, and causes lung inflammation in guinea pigs after 4 daily 3-h exposures. It also produces bronchial hypersensitivity following a single 1-h exposure. The importance of this surface layer is demonstrated by our observation that 200 micrograms/m3 of sulfuric acid droplets of equivalent size are needed to produce the same degree of hypersensitivity. This study characterized the concentration-dependent effects of in vivo exposures to sulfur oxides on arachidonic acid metabolism in the guinea pig lung, and investigated the time course and the relation between eicosanoid composition and pulmonary functions. We focused specifically on four cyclooxygenase metabolites of arachidonic acid, that is, prostaglandins (PG) E1, F2 alpha, 6-keto prostaglandin F1 alpha, and thromboxane (Tx) B2, and two groups of sulfidopeptide leukotrienes (C4, D4, E4, and F4). Guinea pigs were exposed to ultrafine ZnO aerosol (count median diameter = 0.05 microns, sigma g = 1.80) with a layer of acidic sulfur oxide on the surface of the particles. Lung lavage was collected after exposures, and the levels of arachidonic acid metabolites were determined using radioimmunoassay (RIA). Concentration-dependent promotion of PGF2 alpha and concentration-dependent suppression of LtB4 were observed. The increased PGF2 alpha was associated with depressed vital capacity and diffusing capacity of the lungs measured in guinea pigs exposed to the same atmosphere described in a previous study. There is no causal relationship between the levels of other arachidonic acid metabolites and the pulmonary functional changes after exposures to these aerosols

Exposure of guinea pigs 3 hr/day for 5 consecutive days to freshly formed ultrafine zinc oxide (ZnO) (count median diameter: 0.05 micron; geometric standard deviation: 2.0) at a concentration of 7 mg/m3 produced a gradual decrease in total lung capacity and vital capacity over the course of the exposure period. The carbon monoxide (CO) diffusing capacity (DLCO) was not affected until the fourth day, when it dropped abruptly to 30% below control levels. Wet-lung weight/body weight ratios and wet-lung/dry-lung weight ratios increased, indicating the presence of edema. Exposures to 2.7 mg/m3 ZnO, using the same 3 hr/day, 5 day time frame, did not alter any parameters measured. In 2 experiments a single high peak of ZnO (25-34 mg/m3) occurred. In one experiment exposure was stopped, but pulmonary function measurements were made as scheduled; in the other case, exposures to ZnO were continued. In both, lung volumes were decreased abruptly and to a greater extent than when peaks were absent. Continued exposure caused greater decrements in total lung capacity (TLC) and vital capacity (VC) as well as decrements in functional residual capacity (FRC) and residual volume (RV) than were observed when exposure was stopped. Peak exposures reduced DLCO to 45%-60% below control. These values rose to 25%-30% below control with or without continued exposure. Airway resistance increased and compliance decreased following peak exposures. When exposure was stopped, these changes were reversible; with continued exposure they still were different from control levels on the fifth day.(ABSTRACT TRUNCATED AT 250 WORDS)

Effluent gases from high temperature systems such as fossil fuel combustion and pyrometallurgical processes contain inorganic material which has the potential to interact with sulfur dioxide (SO2) on the surface of particles to form an irritant aerosol. The submicron fraction of this inorganic material is especially important as the fine particles may penetrate deep into the lung and cause serious health effects. A laboratory furnace was designed to produce a submicrometer copper oxide aerosol to stimulate emissions from copper smelters and other pyrometallurgical operations. The ultimate aim of this research is to investigate the interaction of SO2 and the copper oxide aerosol at different temperatures and humidities in order to determine the reaction products and their potential health effects upon inhalation. The initial work, as presented in this paper, was to reproducibly generate a submicrometer copper oxide aerosol and to characterize it in terms of size, morphology and composition. Two experimental regimes were set up. One admitted filtered air, without water vapor, into the furnace, and the other admitted filtered air and water vapor. The size and morphology of the aerosols were determined using an electrical aerosol analyzer and transmission electron microscopy. The particles appear as chain aggregates with a count median diameter of 0.026 micron when no water vapor was added and 0.031 micron when water vapor was added into the furnace. Composition of the aerosol was determined using x-ray photoelectron spectroscopy. The aerosol, with or without water in the furnace, consists of a mixture of copper(I) oxide and copper(II) hydroxide

Guinea pigs were exposed head only for 1 hr to submicrometer sodium sulfite aerosols (mass median aerodynamic diameter = 0.36 micron, sigma g = 2.96) at 474, 669, and 972 micrograms SO3(2-)/m3. Respiratory mechanics were measured in unanaesthetized animals before, during, and after exposure. Dose-related increases in resistance and decreases in compliance were observed. At 972 micrograms SO3(2-)/m3, the sodium sulfite aerosol caused a 50% increase in resistance and a 19% decrease in compliance. These changes were still present 1 hr after the end of exposure. The results were used to assess the irritant potency of sodium sulfite aerosol. Another group of guinea pigs was exposed whole body for 1 hr to the same aerosol at 0, 204, 395, and 1152 micrograms SO3(2-)/m3. Immediately after the exposures, lung volume, diffusion capacity for carbon monoxide (DLCO), and wet lung weight were evaluated in anesthetized, tracheotomized animals. As compared to controls, total lung capacity, vital capacity, functional residual capacity, residual volume, and DLCO were all decreased with increasing concentrations of sodium sulfite. Dose-related increases in wet lung weights were also observed. These results were compared with the irritant responses of animals exposed to zinc oxide and sulfur dioxide mixed under different conditions of temperature and humidity