Chemical control of spin-lattice relaxation to discover a room temperature molecular qubit.

The second quantum revolution harnesses exquisite quantum control for a slate of diverse applications including sensing, communication, and computation. Of the many candidates for building quantum systems, molecules offer both tunability and specificity, but the principles to enable high temperature operation are not well established. Spin-lattice relaxation, represented by the time constant T 1, is the primary factor dictating the high temperature performance of quantum bits (qubits), and serves as the upper limit on qubit coherence times (T 2). For molecular qubits at elevated temperatures (>100 K), molecular vibrations facilitate rapid spin-lattice relaxation which limits T 2 to well below operational minimums for certain quantum technologies. Here we identify the effects of controlling orbital angular momentum through metal coordination geometry and ligand rigidity via π-conjugation on T 1 relaxation in three four-coordinate Cu2+ S = ½ qubit candidates: bis(N,N'-dimethyl-4-amino-3-penten-2-imine) copper(ii) (Me2Nac)2 (1), bis(acetylacetone)ethylenediamine copper(ii) Cu(acacen) (2), and tetramethyltetraazaannulene copper(ii) Cu(tmtaa) (3). We obtain significant T 1 improvement upon changing from tetrahedral to square planar geometries through changes in orbital angular momentum. T 1 is further improved with greater π-conjugation in the ligand framework. Our electronic structure calculations reveal that the reduced motion of low energy vibrations in the primary coordination sphere slows relaxation and increases T 1. These principles enable us to report a new molecular qubit candidate with room temperature T 2 = 0.43 µs, and establishes guidelines for designing novel qubit candidates operating above 100 K.

Diagnostic efficiency of the Iowa personality disorder screen items in a nonclinical sample.

The diagnostic efficiency of the 11-item Iowa Personality Disorder Screen (IPDS; Langbehn et al., 1999) was evaluated in a nonclinical sample of young adults, 35% of whom met DSM-III-R criteria for a personality disorder, in a retrospective analysis of SIDP-R data. Results indicated that two IPDS item sets (i.e., combinations of items) produced hit rates of more than 80% along with good sensitivity, specificity, positive predictive power, and negative predictive power. Combined with the findings of Langbehn et al. (1999), these results suggest that the IPDS may be useful as a screening measure for personality disorder in both clinical and nonclinical populations.

Alteration of pulmonary macrophage intracellular pH following inhalation exposure to sulfuric acid/ozone mixtures.

Recent studies have demonstrated that additive and synergistic effects on rabbit pulmonary macrophages (PM phi) function can occur after combined exposures to acid aerosols and ozone. This study investigated intracellular pH (pHi) homeostasis and H+ extrusion mechanisms of PM phi from rabbits exposed to sulfuric acid, ozone, and their mixtures. Animals were exposed for 3 h to 125 micrograms/m3 sulfuric acid, 0.1, 0.3, 0.6 ppm ozone, or combinations of acid with each concentration of ozone, and the pHi was determined by a fluorescent dye ratioing technique. Exposure to 125 micrograms/m3 acid reduced pHi and exposure to ozone resulted in a concentration-dependent reduction in pHi. Ozone generally tended to mitigate the effect of the acid aerosol on pHi. Other groups of rabbits were exposed to 50 micrograms/m3 sulfuric acid, 0.6 ppm ozone, or their mixture, for 3 h, and PM phi were again harvested. The pHi of PM phi following exposure to each of the pollutant atmospheres was not different from control. However, H+ extrusion with an imposed internal acid load was found to be significantly depressed following exposure to either sulfuric acid or ozone alone, while the mixture produced a significant interaction.

Alteration of pulmonary macrophage intracellular pH regulation by sulfuric acid aerosol exposures.

In vivo exposure to sulfuric acid aerosols produces profound effects on pulmonary macrophage (PM phi) phagocytic function and cytokine release and perturbs intracellular pH (pHi) homeostasis. Because pHi influences a multitude of cellular processes, we sought to investigate the mechanism by which acid aerosol exposure affects its regulation. Guinea pigs underwent a single or 5 repeated 3-hr exposures to sulfuric acid aerosol (969 and 974 micrograms/m3 for single and repeated exposures, respectively). PM phi harvested immediately after exposure were incubated in HCO3-free media and their pHi recovery from an intracellular acid load was examined. The overall pHi recovery was depressed after single and multiple exposures to sulfuric acid aerosol. delta pHi (the difference between initial pHi and the one measured at 150 sec) decreased by 15.6 and 23.3% (p < 0.05) for single and repeated exposures, respectively. Initial dpHi/dt (maximum pHi recovery rate) after cytoplasmic acidification diminished by 20.3 and 32.2%, which were not statistically significant (p = 0.08 for repeated exposure). To determine whether the activity of the H(+)-ATPase pump the Na(+)-H+ exchanger was specifically altered by the acid exposures, PM phi were first incubated in Na+ and HCO3-free media with NBD-Cl (7-chloro-4-nitrobenz-2-oxa-1,3-diazol, blocking H(+)-ATPase and leaving only the Na(+)-H+ exchanger in effect) and then challenged with 30 mM NaCl. The pHi recovery of PM phi after Na challenge was significantly reduced in acid aerosol exposed guinea pigs (p < 0.05) compared to controls (for delta pHi, 18.2% lower in single exposure and 22.7% in multiple exposure groups; for initial dpHi/dt, 26.9% lower in single exposure and 22.4% in multiple exposure groups). In contrast, the H(+)-ATPase pump was inconsistently affected as indicated by delta pHi and initial dpHi/dt measured in the presence of MIA (amiloride-5-N-methylisobutyl, inhibiting the Na(+)-H+ exchanger and leaving only the H(+)-ATPase pump in effect). These results suggest that in vivo exposure to sulfuric acid aerosols induces alterations in pHi regulation in guinea pig PM phi attributable to changes in Na(+)-H+ exchanger activity.

Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits.

Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3 hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of fine and ultrafine sulfuric acid aerosols in guinea pigs: alterations in alveolar macrophage function and intracellular pH.

Acidic sulfate is the most toxicologically important sulfur oxide which exists in the ambient air. To determine if particle size influences toxic effects of sulfuric acid, we investigated the effects of sulfuric acid aerosols of two different sizes on biochemical and cellular parameters of bronchoalveolar lavage fluid from exposed guinea pigs. Guinea pigs were exposed to fine (mass median diameter, 0.3 micron), and ultrafine (mass median diameter, 0.04 micron) sulfuric acid aerosols at 300 micrograms/m3 for 3 hr/day. The animals were euthanized immediately and 24 hr after 1 and 4 days of exposure and lungs were lavaged. Elevated beta-glucuronidase, lactate dehydrogenase activities, and total protein concentration as well as decreased cell viability were observed in the lavage after a single exposure to sulfuric acid aerosols of both sizes. These alterations were small, though statistically significant, and transient. No alteration in these parameters was observed after 4 days of exposure to acid aerosols. In contrast, sulfuric acid-induced alterations in alveolar macrophage function were more pronounced and longer lasting. Immediately after a single exposure to fine acid, there was a 2.7-fold increase in the spontaneous tumor necrosis factor (TNF) release over that in the control group while endotoxin-stimulated TNF release was increased by 2.2-fold. In addition, acid aerosols of both sizes increased the TNF release from macrophages after 4 days of exposure, although there was no clear temporal pattern of induction or recovery. Furthermore, immediately after 4 days of exposure to either fine or ultrafine acid, the amount of H2O2 that could be induced from baseline production by alveolar macrophages was 2.2-fold higher than that of the controls. The phagocytic function of macrophages was also altered by exposure to sulfuric acid aerosols. Twenty-four hours after single or multiple exposure, fine acid enhanced (as high as 78% above control) the in vitro phagocytic activity of alveolar macrophages while ultrafine acid depressed the phagocytic capacity (as much as 50% below that in the control). In addition to these biochemical parameters and cellular functions, we also measured the intracellular pH (pHi) of macrophages harvested after exposures to these acid aerosols using a pH-sensitive fluorescent dye. The resting pHi was depressed after a single exposure to both acid aerosols. The depression in pHi persisted 24 hr after ultrafine acid exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Airway hyperresponsiveness in guinea pigs exposed to acid-coated ultrafine particles.

Although several epidemiological studies have provided evidence that airborne sulfate particles can produce adverse health effects in susceptible individuals, there is only limited data demonstrating respiratory effects in human volunteers and experimental animals at near ambient concentrations. We have demonstrated previously that the mixing of metal oxide particles with SO2 under humid conditions produces acid-coated particles that are significantly more potent in causing pulmonary function changes than pure acid droplets. The present study examined the nonspecific airway responsiveness to acetylcholine in guinea pigs exposed to acid-coated zinc oxide particles. One and a half hours after a 1-h exposure to the aerosols or a control atmosphere, pulmonary resistance (RL) was measured in awake, spontaneously breathing animals before and during a challenge with increasing doses of iv acetylcholine (Ach). The provocative infusion rate of Ach that resulted in a 100% increase in RL (PR100) was significantly decreased (p less than .05) in animals exposed to sulfuric acid-coated metal oxide particles (approximately 30 micrograms/m3 sulfate) compared to control animals exposed to furnace gases (79.6 +/- 19.4 vs. 179.6 +/- 16.2 micrograms/kg/min, mean +/- SE, respectively). The PR100 of animals exposed to SO2 (109.1 +/- 45.4) or metal oxide particles (106.7 +/- 38.1) alone was not significantly different from that of furnace gas control animals, indicating that the acid coating on the metal oxide particles and not the particles themselves or the SO2 was responsible for the decrease in the PR100. Moreover, a 10-fold greater amount of total sulfate as a pure aqueous sulfuric acid aerosol was necessary to produce a decrease in PR100 (88.6 +/- 11.0 micrograms/kg/min) equivalent to that produced by coated particles. These results suggest that acute exposure to near-ambient concentrations of sulfuric acid under conditions that promote the formation of acid as a surface coating in respirable particles can induce a nonspecific airway hyperresponsiveness. In a similar manner, a dose-dependent significant decrease in PR100 was also produced in animals exposed to sodium sulfite droplets. Thus a single exposure to different forms of sulfur oxide aerosols can induce an alteration in the responsiveness of airway smooth muscle in the guinea pig.

Sulfuric acid-layered ultrafine particles potentiate ozone-induced airway injury.

Urban air pollution in the United States is composed of a complex mixture of particles and gases. Among the most prominent products of the atmospheric pollutants are sulfur oxides and ozone. In this report, we use two exposure protocols to examine the interaction between exposure to these two pollutants. In the first exposure regimen, guinea pigs were exposed to sulfuric acid (pure sulfuric acid mist or sulfuric acid layered on ZnO) for 1 h. Each exposure is followed 2 h later by another exposure to 0.15 ppm ozone for 1 h. Pulmonary function parameters were measured immediately after the ozone exposure. In guinea pigs that were exposed to 300 micrograms/m3 pure sulfuric acid mist, subsequent exposure to 0.15 ppm ozone did not produce additional change in pulmonary functions. In guinea pigs that were exposed to 84 micrograms/m3 sulfuric acid layered on ZnO, subsequent exposure to 0.15 ppm ozone produced more than additive alterations in vital capacity and diffusing capacity. In the second exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 8 and 9, animals received two additional daily 3-h exposures to 24 micrograms/m3 sulfuric acid layered on ZnO, and pulmonary functions were measured at the end of the daily exposure. Greater reductions in lung volumes and diffusing capacity were observed in animals on d 9 than would be observed in animals that received no additional exposure. In the third exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 9, animals were exposed to 0.15 ppm ozone for 1 h and pulmonary functions were measured at the end of the ozone exposure. Ozone exposure on d 9 induced reductions in lung volumes and diffusing capacity that were not observed in animals receiving exposures to either ozone or sulfuric acid layered ZnO alone. We conclude that single or multiple exposure to sulfuric acid-layered ZnO sensitizes guinea pigs to subsequent sulfuric acid or ozone exposure.

Pulmonary effects of sulfur oxides on the surface of copper oxide aerosol.

The authors have developed a system that generates copper oxide aerosol similar to the primary emissions from smelters. The surface of the ultrafine copper oxide aerosol is coated with a layer of sulfur oxides consisting of sulfate, S(VI), and sulfite, S(IV). Guinea pigs were exposed to this sulfur oxide layered copper oxide aerosol, and pulmonary mechanical functions were measured by using the Amdur-Mead method. The concentration of sulfur oxides on the aerosol was determined by using a flame photometric detector system. Although sulfuric acid was not found in this system, S(IV) at concentrations as low as 0.36 mumol/m3 delivered as a surface layer caused prolonged changes in pulmonary mechanical functions.

Pulmonary effects of ultrafine coal fly ash inhaled by guinea pigs.

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.

Health effects of air pollutants: sulfuric acid, the old and the new.

Data from exposure of experimental animals and human subjects to sulfuric acid presents a consistent picture of its toxicology. Effects on airway resistance in asthmatic subjects were well predicted by data obtained on guinea pigs. Sulfuric acid increases the irritant response to ozone in both rats and man. In donkeys, rabbits, and human subjects, sulfuric acid alters clearance of particles from the lung in a similar manner. These changes resemble those produced by cigarette smoke and could well lead to chronic bronchitis. Data obtained on guinea pigs indicate that very small amounts of sulfuric acid on the surface of ultrafine metal oxide aerosols produce functional, morphological, and biochemical pulmonary effects. Such particles are typical of those emitted from coal combustion and smelting operations. Sulfate is an unsatisfactory surrogate in existing epidemiology studies. Sulfuric acid measurement is a critical need in such studies.

Furnace-generated acid aerosols: speciation and pulmonary effects.

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.

Effects of sulfur oxides on eicosanoids.

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.

Changes in pulmonary lavage fluid of guinea pigs exposed to ultrafine zinc oxide with adsorbed sulfuric acid.

Ultrafine metal oxide particles (diameters less than 0.1 microns) and sulfur dioxide are important products of coal combustion. Interaction of these products in the effluent stream results in formation of ultrafine particles with adsorbed sulfur compounds, including sulfuric acid. The toxicity of ultrafine zinc oxide particles with adsorbed sulfuric acid was evaluated by comparing pulmonary lavage fluid from guinea pigs exposed for 1, 2, 3, 4, or 5 consecutive daily 3-h periods to ultrafine zinc oxide generated in the presence of sulfur dioxide (ZnO + SO2) to pulmonary lavage fluid from guinea pigs exposed to an equivalent concentration of ultrafine ZnO. Two groups of guinea pigs exposed either to SO2 or to particle-free furnace gas served as additional controls. Cells, protein, and activities of lactate dehydrogenase, acid phosphatase, and alkaline phosphatase were increased in lavage fluid obtained from guinea pigs exposed to ZnO + SO2 as compared to guinea pigs exposed to ZnO. These results demonstrate the potential importance of ultrafine metal oxides as carries of sulfuric acid derived from fossil fuel combustion.

Pulmonary function of guinea pigs exposed to freshly generated ultrafine zinc oxide with and without spike concentrations.

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)

Copper oxide aerosol: generation and characterization.

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.

Indomethacin and cromolyn sodium alter ozone-induced changes in lung function and plasma eicosanoid concentrations in guinea pigs.

Male Hartley guinea pigs were given either indomethacin (IN), cromolyn sodium (CS), or no drug (ND) and then exposed either to filtered air or to 1 ppm ozone (O3) for 1 hr. At 2 or 24 hr postexposure, ventilation, respiratory mechanics, lung volumes, carbon monoxide-diffusing capacity (DLCO), and alveolar volume (VA) were measured, and in separate groups of animals, plasma eicosanoids (EC) were measured. Both drugs blocked the increase in flow resistance noted at 2 hr after O3 and prevented O3-induced increases in the wet lung weight to body weight ratio seen at 2 and 24 hr in the ND group. In the ND animals O3 also decreased total lung capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and residual volume (RV). IN as well as CS blocked reductions in FRC and RV at both 2 and 24 hr after O3. TLC was reduced by both drug treatments in air- and O3-exposed animals. CS treatment also decreased VC in all groups. IN blocked reductions in VA after O3 but did not prevent decreases in DLCO. CS blocked reductions in both VA and DLCO after O3, but the drug decreased DLCO in air-exposed animals. The prostaglandins PGF2 alpha and 6-keto PGF1 alpha were largely unaffected by O3 exposure or drug treatment. Prostaglandin E1 (PGE1) was not affected by O3, but both drugs significantly increased PGE1 in all exposure groups. Effects on plasma thromboxane B2 (TxB2) were variable although in most groups TxB2 was lower than in the O3-exposed ND groups. Although our findings suggest that both drugs block some effects of O3 exposure on the lungs and on plasma EC concentrations, the degree to which EC contribute to O3-induced pulmonary effects is not clearly apparent.

Lung injury in guinea pigs caused by multiple exposures to ultrafine zinc oxide: changes in pulmonary lavage fluid.

Metal oxide particles with diameters of less than 0.1 micron (ultrafine particles) are important products of fossil fuel combustion. Pulmonary lavage fluid was obtained from guinea pigs given 1, 2, or 3 consecutive, daily, 3-h, nose-only exposures to 0, 2.3, 5.9, or 12.1 mg/m3 of freshly generated zinc oxide (ZnO) particles with a projected area diameter of 0.05 micron. Exposure to ZnO at 5.9 or 12.1 mg/m3 was associated with increased protein, neutrophils, and activities of angiotensin-converting enzyme, alkaline phosphatase, acid phosphatase and lactate dehydrogenase in lavage fluid, and with histologic evidence of pulmonary damage characterized by centriacinar inflammation. The severity of inflammation, graded by the number of inflammatory foci per square centimeter of lung, correlated with the amount of protein and the activity of angiotensin-converting enzyme and other enzymes in lavage fluid. These results indicate that analysis of pulmonary lavage fluid is a useful and sensitive method for quantitative evaluation of pulmonary damage caused by inhalation of low levels of ultrafine ZnO.

Functional changes in the lungs of guinea pigs exposed to sodium sulfite aerosols.

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.

Effect of ozone exposure on lung functions and plasma prostaglandin and thromboxane concentrations in guinea pigs.

Male Hartley guinea pigs were exposed either to filtered air or to 1 ppm ozone (O3) for 1 hr. At 2, 8, 24, or 48 hr after exposure we measured ventilation, respiratory mechanics, lung volumes, diffusing capacity for carbon monoxide (DLCO), and alveolar volume (VA) in anesthetized, tracheotomized animals. Respiratory frequency and tidal volume were unchanged in all groups. Pulmonary resistance was increased 2 hr after O3 but returned to control at 8 hr and thereafter. Prolonged reductions in lung volumes (total lung capacity, vital capacity, functional residual capacity, and residual volume) as well as in DLCO and VA occurred after O3, with maximum decreases at 8 and 24 hr postexposure. Increased ratios of wet lung weight to body weight were seen at 2, 8, and 24 hr. In separate groups of animals, also exposed either to filtered air or to 1 ppm O3, plasma eicosanoid (EC) concentrations were measured at 2, 8, 24, 48, or 72 hr after exposure. Significant increases in thromboxane B2 concentrations were seen at 2, 24, and 48 hr after exposure. Plasma concentrations of 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin E1 (PGE1) were increased at 24 hr and at 24, 48, and 72 hr, respectively. The nature of this long-term pulmonary response to a short-term exposure to O3 suggests alveolar involvement, including probable alveolar duct constriction and localized pulmonary edema. Although changes in plasma EC concentrations were observed concurrent with impaired lung functions, no simple causal relationship was apparent from these studies.