Seasonal distribution and modeling of diesel particulate matter in the Southeast US.

The fine and ultra fine size of diesel particulate mater (DPM) are of great health concern and significantly contribute to the overall cancer risk. In addition, diesel particles may contribute a warming effect on the planet's climate. The composition of these particles is composed principally of elemental carbon (EC) with adsorbed organic compounds, sulfate, nitrate, ammonia, metals, and other trace elements. The purpose of this study was to depict the seasonality and modeling of particulate matter in the Southeastern US produced by the diesel fueled sources (DFSs). The modeling results came from four one-month cases including March, June, September, and December to represent different seasons in 2003 by linking Models-3/CMAQ and SMOKE. The 1999 National Emissions Inventory Version 3 (NEI99) was used in this analysis for point, area, and non-road sources, whereas the National Mobile Inventory Model (NMIM) was used to create the on-road emissions. Three urban areas, Atlanta, Birmingham, and Nashville were selected to analyze the DPM emissions and concentrations. Even though the model performance was not very strong, it could be considered satisfactory to conduct seasonal distribution analysis for DPM. Important hourly DPM seasonality was observed in each city, of which higher values occurred at the morning traffic rush hours. The EC contributions of primary DPM were similar for all three sites (approximately 74%). The results showed that there is no significant daily seasonality of DPM contribution to PM(2.5) for any of these three cities in 2003. The annual DPM contribution to total PM(2.5) for Atlanta, Nashville, and Birmingham were 3.7%, 2.5%, and 2.2%, respectively.

Tobacco abuse and its treatment. Turning old and new issues into opportunities for the occupational health nurse.

1. Tobacco use is linked to excessive rates of cardiovascular disease, lung disease, and many fatal neoplasms. In the United States it is the number one cause of illness and premature death. Cigarettes and other combusted forms of tobacco generate environmental tobacco smoke, a major contributor to asthma attacks, heart attacks, and lung cancer among nonsmokers. 2. Cigarettes are the most prevalent and abused form of tobacco, but other forms, such as cigars and smokeless tobacco, also contain nicotine and may cause dependency in high risk groups that consume these products. 3. The addictiveness of tobacco products, especially cigarettes, is particularly detrimental to vulnerable groups such as youth, women, blue collar workers, and other high risk and economically disadvantaged populations. 4. Effective treatment programs (e.g., individual and group counseling, close monitoring, drug treatment) are available to treat nicotine dependency, but many health care providers have been reluctant to educate their patients and clients about these programs. 5. Workplace tobacco use treatment programs, along with policies to restrict tobacco use, have special merit for employers concerned with worker health and safety, productivity, and profitability. Even the more successful tobacco treatment programs perform better when combined with additional efforts to reduce worker health risks and promote well being.

Prolonged, intravenous paraquat infusion in the rat. I. Failure of coinfused putrescine to attenuate pulmonary paraquat uptake, paraquat-induced biochemical changes, or lung injury.

Paraquat (PQ) was administered to rats for 7 days by iv infusion from osmotic minipump at dosage rates of 250 and 500 nmol PQ/hr. The efficacy of putrescine in attenuating pulmonary PQ accumulation in vivo and the resulting PQ-induced biochemical changes and lung injury were assessed in these animals by coinfusion of putrescine at rates of 2500 or 5000 nmol/hr. Dose-dependent, steady-state blood levels of both PQ and putrescine were achieved by 18 hr and maintained throughout the infusion period. Lung PQ content at 7 days was dose-dependent and up to 18-fold greater than corresponding blood levels. No evidence of toxicity was observed in low-dose PQ animals while weight loss and overt toxicity was observed in high-dose PQ rats between Days 4 and 5. Histopathological examination of high-dose PQ rat lungs revealed qualitative changes typical of PQ toxicity. Significant (p less than 0.05) increases in lung glutathione and activities of glucose-6-phosphate dehydrogenase and GSSG reductase resulted from both PQ doses, reflecting PQ-induced oxidant stress and increased demand on lung NADPH. A net decrease in lung NADPH (p less than 0.05) was directly measured in high-dose PQ rats and may have contributed to the PQ-induced lung injury. Although putrescine is an effective inhibitor of pulmonary PQ uptake in vitro, the blood putrescine levels achieved in this study did not appear to inhibit this process in vivo. This was evidenced by putrescine's failure to decrease 7-day lung PQ content, PQ-induced biochemical changes, or lung injury.

Prolonged, intravenous paraquat infusion in the rat. II. Paraquat-induced alterations in lung polyamine metabolism.

The effects of paraquat (PQ) on lung putrescine, spermidine, and spermine levels, and ornithine decarboxylase (ODC) activity were assessed in rats after 7 days of iv infusion of the herbicide via osmotic minipump. Paraquat administration at a rate of 250 nmol/hr [673 +/- 40 nmol/kg/hr (n = 15)] had no effect on these parameters. In contrast, significant (p less than 0.05) elevations in lung putrescine (407% of control), spermidine (202% of control), and ODC activity (174% of control were measured in lungs of rats given 500 nmol PQ/hr [1.31 +/- 0.53 mumol/kg/hr (n = 14)]. Since evidence of lung damage was, likewise, observed only in the high-dose PQ rats, these changes in polyamine metabolism could have been a nonspecific response to PQ-induced lung injury rather than a direct biochemical effect of PQ. The results suggest that stimulation of polyamine biosynthesis may play an important role in PQ-induced lung injury. This role may involve regulation of repair mechanisms or, conversely, the polyamines may actually mediate PQ-induced fibrotic changes in the lung.

Immune responsiveness of monkeys exposed chronically to cigarette smoke.

Eleven adult male stumptailed monkeys (Macaca arctoides) were chronically exposed to either a low dose (human equivalent of 1 pack/day) or a high dose (human equivalent of 3 packs/day) of high-tar, high-nicotine University of Kentucky reference cigarette smoke for 4-8 years. Several parameters of their immunological response were compared to six nonsmoked control animals. The results from these experiments suggest that cigarette smoking does not significantly affect the response of spleen cells to the mitogens phytohemagglutinin or lipopolysaccharide. However, spleen cells from animals subjected to the heavy dose of cigarette smoke demonstrated a significant reduction in their natural killer cell-mediated lytic activity and a decreased response to concanavalin A. These results suggest that cigarette smoking may have a differential effect on lymphocyte subpopulations, and that the effects on the immune response are related to the dose of cigarette smoke.

Glutathione status of isolated rabbit lungs. Effects of nitrofurantoin and paraquat perfusion with normoxic and hyperoxic ventilation.

Thirty-minute perfusion of isolated rabbit lungs with a Krebs-Ringer bicarbonate buffer containing 420 microM paraquat (PQ) or nitrofurantoin (NF) resulted in increases in lung oxidized glutathione (GSSG) content of 589 and 2656%, respectively, over control levels. The degree of glutathione efflux was also increased with both agents, i.e. 77 and 238% above control leakage for PQ and NF respectively. The pulmonary toxicity of both compounds is known to be heightened by conditions of hyperoxia(O2). Ventilation of lungs with 95% O2-5% CO2 did not, in itself, significantly alter glutathione efflux, GSH or GSSG levels. However, ventilation with 95% O2-5% CO2 increased lung GSSG levels in PQ-perfused lungs 225% over PQ-air-perfused lungs, a combined effect not observed with NF-O2, wherein mean GSSG levels were only 72% of that observed with NF-air. Glutathione efflux in PQ-O2-treated lungs declined somewhat (20%) compared to that observed with PQ-air, but a significant increase in the amount of glutathione efflux was seen with NF-O2-treated lungs, i.e. 120 and 310%, respectively, over that attributable to NF or O2 alone. Although the biochemical mechanisms of toxicity of these compounds are thought to be very similar, the disparate degree of GSH oxidation observed with equimolar levels of PQ and NF may indicate differences in reactivity towards glutathione and other lung sulfhydryl pools. The stimulation of the oxidative effects of PQ and NF on lung GSH due to hyperoxic ventilation may be related to the reported O2 enhancement of their toxicity.

Plasma and liver carnitine (free and esterified) levels and their interrelationships in moderately hypercholesterolemic monkeys (Macaca arctoides).

The level of carnitine and its esters was measured in plasma and liver in 20 male stump-tailed monkeys (Macaca arctoides) that were fed a moderately hypercholesterolemic diet. Plasma total carnitine was 60 +/- 3 nmol/mL (30% esterified) and liver total carnitine was 254 +/- 15 nmol/g wet weight (16% esterified) or 1.28 +/- 0.07 nmol/mg noncollagen protein. The plasma concentration of total carnitine was positively correlated with the total carnitine concentration of the livers (r = 0.71, p less than 0.001). Additionally, there was a positive correlation between plasma esterified carnitine and liver esterified carnitine (r = 0.92, p less than 0.001) as well as between plasma esterified carnitine and plasma beta-hydroxybutyrate (r = 0.92, p less than 0.001), which together suggest that plasma esterified carnitine in the monkeys was largely of hepatic origin. There was no significant correlation between plasma carnitine (total, free, or esterified) and body mass, plasma triglycerides, or plasma cholesterol.

Failure of chronic cigarette smoke exposure to alter plasma lipoproteins of stumptailed macaques (Macaca arctoides).

Twenty-one 8-14 kg adult male stumptailed macaques, Macaca arctoides, were fed a standard laboratory diet and divided into 3 groups. The high-dose group and low-dose group were exposed to cigarette smoke at the human equivalent of 3 packs and 1 pack per day, respectively, 7 days per week, for 3-5 years. Eight animals served as cage an sham controls. Peak blood carboxyhemoglobin (COHb) levels measured immediately after smoking showed levels of 0.5+/- 0.1%, 3.6+/-1.0%, and 5.7+/-2.8% for sham controls, low, and high dose smokers, respectively. Hemoglobin and hematocrit values were 2-7% higher (N.S. to P less than 0.05) for smoking groups, presumably as a consequence of chronically elevated COHb levels. No significant differences were seen in total plasma cholesterol and lipoprotein cholesterol concentration measured at four intervals over period of one year. We conclude from these data that, while fed a low fat diet, chronic cigarette smoke inhalation fails to alter plasma lipoprotein levels in this animal model.

Effects of nitrofurantoin on the glutathione redox status and related enzymes in the isolated, perfused rabbit lung.

Nitrofurantoin (NF) is a urinary antimicrobial drug which causes pulmonary injury. We measured levels of total lung glutathione (TLG), a tripeptide central to cellular antioxidant defenses and xenobiotic detoxification, and enzyme activities related to maintenance and utilization of reduced glutathione (GSH) in isolated, New Zealand white rabbit lungs perfused with a Kreb's-Ringer's bicarbonate medium containing NF (420 microM). After 30 minutes there was no net difference in the level of TLG [GSH + GSSG(oxidized) + effluent GSH-GSSG] or total nonprotein sulfhydryls in NF-perfused or control lungs. However, there was a decrease in the GSH:GSSG redox ratio to 2% of control (P less than .0005) and an 87% increase in GSH-GSSG efflux (P less than .005). This increased oxidation of GSH indicates that toxicity of NF is likely oxidative in nature, possibly via redox cycling of NF in the presence of oxygen to generate activated oxygen species. Activities of glucose-6-phosphate and 6-phosphogluconate dehydrogenases, GSH reductase, and GSH S-transferase were not significantly different due to NF perfusion. GSH peroxidase activity decreased 34% (P less than .025) in NF-perfused lungs. Because all TLG, as well as total nonprotein thiol was accounted for in NF-perfused lungs, it would appear that no GSH-NF metabolite conjugation occurred. GSH metabolic conjugation in the perfused lung is easily detected when tissue-alkylating drugs or their metabolites are present.

Ozone interaction with rodent lung. III. Oxidation of reduced glutathione and formation of mixed disulfides between protein and nonprotein sulfhydryls.

Nonprotein sulfhydryls (NPSH), a major source of cellular reducing substances, were examined in lung tissue after short-term exposure of rats to O3. While the NPSH level was unaffected by low-level exposures (e.g., 0.8 ppm for up to 24 h or 1.5 ppm for up to 8 h), it was significantly lowered by higher exposure regimens (e.g., 25 per cent after 2 ppm for 8 h and 49 per cent after 4 ppm for 6 h). After exposure to 4 ppm O3 for 6 h the level of reduced glutathione (GSH), which accounted for approximately 90 per cent of NPSH in the lung, decreased 40 per cent but without a rise in the level of oxidized gluathione (GSSG). Treatment of lung homogenate with borohydride led to recovery of NPSH in exposed lungs to control values, suggesting that NPSH or GSH oxidation during in vivo O3 exposure resulted in formation of mixed disulfides with other sulfhydryl (SH) groups of lung tissue. Extracts of borohydride-treated particulate and supernatant fractions of lung homogenate were analyzed for NPSH by paper chromatography. From this analysis GSH appeared to be the only NPSH bound to lung tissue proteins via mixed disulfide linkage. The formation of mixed disulfides appeared to be a transient phenomenon. Immediately after a 4-h exposure to 3 ppm O3 the level of mixed disulfides was small (15 per cent of the total NPSH) but attained a peak (equivalent to 0.6 mumol NPSH/lung) after a recovery for 24 h. However, the level diminished considerably within 48 h of recovery.