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Ecologic regression analysis and the study of the influence of air quality on mortality.

This presentation focuses entirely on the use and evaluation of regression analysis applied to ecologic data as a method to study the effects of ambient air pollution on mortality rates. Using extensive national data on mortality, air quality and socio-economic status regression analyses are used to study the influence of air quality on mortality. The analytic methods and data are selected in such a way that direct comparisons can be made with other ecologic regression studies of mortality and air quality. Analyses are performed by use of two types of geographic areas, age-specific mortality of both males and females and three pollutants (total suspended particulates, sulfur dioxide and nitrogen dioxide). The overall results indicate no persuasive evidence exists of a link between air quality and general mortality levels. Additionally, a lack of consistency between the present results and previous published work is noted. Overall, it is concluded that linear regression analysis applied to nationally collected ecologic data cannot be used to usefully infer a causal relationship between air quality and mortality which is in direct contradiction to other major published studies.

Air Pollutants↗

An association between fine particles and asthma emergency department visits for children in Seattle.

Asthma is the most common chronic illness of childhood and its prevalence is increasing, causing much concern for identification of risk factors such as air pollution. We previously conducted a study showing a relationship between asthma visits in all persons < 65 years of age to emergency departments (EDs) and air pollution in Seattle, Washington. In that study the most frequent zip codes of the visits were in the inner city. The Seattle-King County Department of Public Health (Seattle, WA) subsequently published a report which showed that the hospitalization rate for children in the inner city was over 600/100,000, whereas it was < 100/100,000 for children living in the suburbs. Therefore, we conducted the present study to evaluate whether asthma visits to hospital emergency departments in the inner city of Seattle were associated with outdoor air pollution levels. ED visits to six hospitals for asthma and daily air pollution data were obtained for 15 months during 1995 and 1996. The association between air pollution and childhood ED visits for asthma from the inner city area with high asthma hospitalization rates were compared with those from lower hospital utilization areas. Daily ED counts were regressed against fine particulate matter (PM), carbon monoxide (CO), sulfur dioxide, and nitrogen dioxide using a semiparametric Poisson regression model. Significant associations were found between ED visits for asthma in children and fine PM and CO. A change of 11 microg/m3 in fine PM was associated with a relative rate of 1.15 [95% confidence interval (CI), 1.08-1.23]. There was no stronger association between ED visits for asthma and air pollution in the higher hospital utilization area than in the lower utilization area. These findings were seen when estimated PM2.5 concentrations were below the newly adopted annual National Ambient Air Quality Standard of 15 microg/m3.

Adolescent↗

[Relationship between low birthweight and air pollution in the city of Sao Paulo, Brazil].

OBJECTIVE: Air pollution has been investigated as a potential determinant for low birthweight. The aim of the present study was to study the effect of air pollution on birthweight. METHODS: We analyzed all deliveries by mothers living in the municipality of Sao Paulo, Southeastern Brazil, between 1998 and 2000. We estimated the prevalence of low birthweight according to newborn, mother, and delivery characteristics. Only births occurring in the most central districts of the city were analyzed, totaling 311.735 events. For the evaluation of the effects of air pollution, we excluded preterm and multiple deliveries. Pollutants analyzed were ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), suspended particles (PM10), and carbon monoxide (CO). The effect of maternal exposure to air pollution on birthweight was evaluated using linear and logistic regression. RESULTS: A total of 4.6% of newborns weighed less than 2,500 g at birth. Maternal exposure to CO, PM10, and NO2 during the first trimester of pregnancy was significantly associated with decreased birthweight. CONCLUSIONS: Our results reinforce the notion that maternal exposure to air pollution during the first trimester of pregnancy may contribute to lesser weight gain in the fetus.

Adult↗

[Air pollutants and their monitoring].

Some basic concepts regarding air pollution are set out. Although, from a health care standpoint, our interest revolves around the impact which pollution has on human health, it being important to ascertain the main pollutants, the sources of emissions, the physiochemical properties thereof, the sampling and analysis methods which are used at the air pollution control stations, the limits set by the laws currently in impact and the World Health Organization recommendations with regard to the levels of immission. This study reviews these concepts with regard to the pollutants which have been analyzed in the Spanish Multicenter Study of Air Pollution and Mortality (EMECAM): particles, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3). For this purpose, the most recent publications on this subject have been used, including part of what is going to be the line around which all of the measures aimed at combating air pollution are going to be revolving in the very near future, that is, the new set of European Union Directives (some currently in the proposal stage) and the latest recommendations (not as yet published) of the World Health Organization. Lastly, a wide range of aspects are set out which involve Public Health in the field of air pollution, despite the monitoring and control thereof falling to the environmental affairs authorities in terms of government organization.

Air Pollutants↗

[The short-term effects of air pollution on mortality. The results of the EMECAM project in the city of Valencia, 1994-96. Estudio Multcéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad].

BACKGROUND: To determine the short-term impact of air pollution on mortality in the city of Valencia throughout the 1994-1996 period by employing the analysis method of the Spanish multicenter study with regard to the relationship between air pollution and the mortality (EMECAM Project). METHODS: The daily levels of black smoke, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3) were obtained from the Valencia air pollution monitoring network. The death rate indicators analyzed were the daily number of death due to all causes, except the external ones, the deaths of those over age 70, and the deaths resulting from respiratory and cardiovascular diseases. Following the methods of the EMECAM Project, autoregressive Poison regression models were built up, controlling the different confounding factors (seasonality, trend, calendar, weather variables and flu impact). RESULTS: For total mortality except the external ones, a significant impact of black smoke (RR 10 micrograms/m3: 1.013; CI95% 1.003 to 1.023) and for CO 24 la (RR 1 mg/m3: 1.024; CI95% 1.003 to 1.046) was found. For the mortality of those individuals over 70, the estimated impact was somewhat greater than for black smoke (RR 10 micrograms/m3: 1.017; CI95% 1.005-1.029), as well as for CO2 1 h (RR 10 micrograms/m3: 1.007; CI95% 1.001-1.013). No significant relationship was found with the mortality due to respiratory or cardiovascular diseases for the entire period. CONCLUSIONS: The current levels of pollution in the city of Valencia show a significant impact on daily mortality. These findings are consistent with the previous research and are coherent with those obtained on analyzing the relationship between air pollution and morbidity indicators.

Aged↗

Outdoor air pollution in urban areas and allergic respiratory diseases.

Respiratory allergic diseases (rhinitis, rhinosinusitis, bronchial asthma and its equivalents) appear to be increasing in most countries, and subjects living in urban and industrialized areas are more likely to experience respiratory allergic symptoms than those living in rural areas. This increase has been linked, among various factors, to air pollution, which is now an important public health hazard. Laboratory studies confirm the epidemiological evidence that inhalation of some pollutants, either individually or in combination, adversely affect lung function in asthmatics. The most abundant air pollutants in urban areas with high levels of vehicle traffic are respirable particulate matter, nitrogen dioxide and ozone. While nitrogen dioxide does not exert consistent effects on lung function, ozone, respirable particulate matter and allergens impair lung function and lead to increased airway responsiveness and bronchial obstruction in predisposed subjects. However, besides acting as irritants, airborne pollutants can modulate the allergenicity of antigens carried by airborne particles. By attaching to the surface of pollen grains and of plant-derived paucimicronic particles, pollutants can modify the morphology of these antigen-carrying agents and after their allergenic potential. In addition, by inducing airway inflammation, which increases airway epithelial permeability, pollutants overcome the mucosal barrier and so facilitate the allergen-induced inflammatory responses. Moreover, air pollutants such as diesel exhaust emissions are thought to modulate the immune response by increasing immunoglobulin E synthesis, thus facilitating allergic sensitization in atopic subjects and the subsequent development of clinical respiratory symptoms.

Air Pollution↗

[Short-term effects of exposure to urban air pollution on human health in Europe. The APHEA Projects (Air Pollution and Health: a European Approach].

During the '80s, evidence was collected that air pollutants concentrations close to, or lower than, air quality standards could negatively influence public health at short term, i.e. within a few days. The European Union financed, between 1993 and 1995, the study "Short term effects of Air Pollution on Health: a European Approach using epidemiological time-series data" (APHEA-1 project), involving more than 25 millions inhabitants in 15 cities, investigated between 1977 and 1991. In this paper, the main results, already published in various scientific journals, are reported. The health effects were studied as mortality for natural causes, cardiovascular and respiratory diseases, and as emergency hospital admissions for all respiratory diseases, bronchial asthma, and chronic obstructive pulmonary disease (COPD). The pollutants whose measures were available for the analysis are sulphur dioxide (SO2), nitrogen dioxide (NO2), particulate matter (PM) measured either as black smoke or total suspended particulate, and ozone (O3). The analysis was carried out by each participating group following a detailed protocol, defined during various workshops, through the construction of Poisson regression models, adjusted for autocorrelation and overdispersion, accounting for variables influencing the daily count of deaths, such as long time trends, season, temperature, day of the week. This paper reports the results of the meta-analysis, performed using the values of each city, as relative risk of dying or being admitted to hospital associated with increases of 50 micrograms/m3 in the 24 hours average concentrations of each pollutant. The daily number of natural deaths was associated with increases in the levels of PM, SO2, O3, and NO2. Cardiovascular and respiratory deaths were associated with increases of the levels of PM, SO2, and O3; cardiovascular deaths were associated also with increases of NO2 concentrations. Emergency hospital admissions for the whole group of respiratory disorders are less consistently associated with PM, SO2, and NO2, whereas there is evidence of association with O3. COPD admissions are related to the air pollutant levels, especially those of O3. Lastly, NO2 levels may play a role in exhacerbating asthma, and SO2 levels can have an effect on asthma in children. A second study is currently going on, involving over 40 millions residents in 34 cities. The aims of this project are: to evaluate the dose-response relationship, to investigate on synergy among pollutants, on the "harvesting" phenomenon, on the geographical differences inside Europe and with the U.S. through the collaboration with a similar American study now in progress. The existence of an association between daily variations in the levels of urban air pollution and adverse health effects was confirmed in Europe. This association is weak, but it involves the whole resident population, so it is a major cause of concern from the public health point of view.

Adolescent↗

Daily mortality and fine and ultrafine particles in Erfurt, Germany part I: role of particle number and particle mass.

Increases in morbidity and mortality have been observed consistently and coherently in association with ambient air pollution. A number of studies on short-term effects have identified ambient particles as a major pollutant in urban air. This study, conducted in Erfurt, Germany, investigated the association of mortality not only with ambient particles but also with gaseous pollutants and indicators of sources. Part I of this study concentrates on particles. Data were collected prospectively over a 3.5-year period from September 1995 to December 1998. Death certificates were obtained from the local authorities and aggregated to daily time series of total counts and counts for subgroups. In addition to standard data for particle mass with diameters < or = 2.5 microm (PM2.5)* or < or = 10 microm (PM10) from impactors, a mobile aerosol spectrometer (MAS) was used to obtain size-specific number and mass concentration data in six size classes between 0.01 microm and 2.5 microm. Particles smaller than 0.1 microm were labeled ultrafine particles (three size classes), and particles between 0.1 and 2.5 microm were termed fine particles (three size classes). Concentrations of the gases sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) were also measured. The daily average total number concentration was 18,000 particles/cm3 with 88% of particles below 0.1 pm and 58% below 0.03 microm in diameter. The average mass concentration (PM2.5) was 26 microg/m3; of this, 75% of particles were between 0.1 and 0.5 microm in diameter. Other average concentrations were 38 microg/m3 for PM10, 17 microg/m3 for SO2, 36 microg/m3 for NO2, and 600 microg/m3 for CO. Ambient air pollution demonstrated a strong seasonality with maximum concentrations in winter. Across the study period, fine particle mass decreased, whereas ultrafine particle number was unchanged. The proportion of ultrafine particles below 0.03 microm diameter increased compared with the proportion of other particles. During the study, concentrations of SO2 and CO also decreased, whereas the concentration of NO2 remained unchanged. The data were analyzed using Poisson regression techniques with generalized additive modeling (GAM) to allow nonparametric adjustment for the confounders. Both the best single-day lag and the overall association of multiple days fitted by a polynomial distributed lag model were used to assess the lag structure between air pollution and death. Mortality increased in association with level of ambient air pollution after adjustment for season, influenza epidemics, day of week, and weather. In the sensitivity analyses, the results proved stable against changes of the confounder model. We saw comparable associations for ultrafine and fine particles in a distributed lag model where the contribution of the previous 4 to 5 days was considered. Furthermore, the data suggest a somewhat more delayed association of ultrafine particles than of fine particles if single-day lags are considered. The associations tended to be stronger in winter than in summer and at ages below 70 years compared to ages above 70 years. Analysis of the prevalent diseases mentioned on death certificates revealed that the overall association for respiratory diseases was slightly stronger than for cardiovascular diseases. In two-pollutant models, associations of ultrafine and fine particles seemed to be largely independent of each other, and the risk was enhanced if both were considered at the same time. Furthermore, when the associations were summed for the six size classes between 0.01 and 2.5 microm, the overall association was clearly stronger than the associations of the individual size classes alone. Associations were observed for SO2, NO2, and CO with mortality despite low concentrations of these gases. These associations disappeared in two-pollutant models for NO2 and CO, but they remained stable for SO2. The persistence of the SO2 effect was interpreted as artifact, however, because the SO2 concentration was much below levels at which effects are usually expected. Furthermore, the results for SO2 were inconsistent with those from earlier studies conducted in Erfurt. We conclude that both fine particles (represented by particle mass) and ultrafine particles (represented by particle number) showed independent effects on mortality at ambient concentrations. Comparable associations for gaseous pollutants were interpreted as artifacts of collinearity with particles from the same sources.

Adolescent↗

[Atmosphere air pollution and health of Kaunas children].

Many studies support the impact of long-term exposure to air pollution on respiratory and allergic symptoms and illnesses. The aim of the study was to assess the prevalence of respiratory and allergic symptoms and illnesses in children living in 4 districts of Kaunas, to estimate the indices of respiratory function and to assess the relationship between mentioned indices and air pollutants such as dust, sulfur dioxide and nitrogen dioxide. A cross-sectional survey included 840 Kaunas children (34 subjects in Senamiestis, 288 in Zaliakalnis, 128 in Petrasiūnai and 390 in Silainiai) aged 6-7 years, whose parents filled out the questionnaire and children performed respiratory function test. Response rate varied from 58.6 percent to 69.2 percents depending on district. Questionnaire of International Study of Asthma and Allergy in Childhood (ISAAC) was used. The parameters of respiratory function (FVC, FEV1, FEV1/FVC, MEF25, MEF50, MEF75, PEF) were measured with Pony Graphics 3.5. The data showed that prevalence of respiratory and allergic symptoms and illnesses in children living in 4 districts of Kaunas did not differ significantly. In most of the cases it was similar to that found in Riga and Tallinn. There is a significant relationship between MEF25, MEF50, MEF75, PEF and sex as well as gas for cooking.

Age Factors↗

Trend of air pollution and its effect on human health in Hiroshima Prefecture--a retrospective study in the cities of Otake, Kure, Mihara, Takehara, Fukuyama and Kaita Town, 1977-1992.

The evaluation of adverse health effects resulting from exposure to relatively low levels of ambient air pollution is currently a major concern. By using methodology that directly addressed the time series nature of data, this study investigated the association between ambient air pollution and respiratory symptoms and eye, nose, throat irritation symptoms. Health effects were determined by using the air quality data from ambient monitoring stations located within the Hiroshima Prefecture area. The air pollution data chosen for this study were the mean of annual average concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), suspended particulate matter (SPM) and photochemical oxidants (Ox). The health data were extracted from the Hiroshima Community Health Study conducted in the cities of Otake, Kure, Takehara, Mihara, Fukuyama and Kaita Town during 1977-1992. The Community Health Study data were obtained by using a Japanese translation of the British Medical Research Council (BMRC) Questionnaire. The analysis was limited to the investigation of the health symptoms reported by subjects and the mean annual average concentrations of ambient air pollution in each study area. The results indicated a significant association between SO2 levels and lacrimacy symptoms (p < 0.05), runny nose (p < 0.05) and cough symptoms (p < 0.05). This study also found a significant association between O(x) and phlegm symptoms reported by the subjects (p < 0.01). In contrast, the results found that there was a negative correlation between NO2 levels and phlegm symptoms reported by subjects. In conclusion, moderate annual changes in SO2 and O(x) levels induce a significant increase of health symptoms in the local community.

Adult↗

Pulmonary endocrine cell hyperplasia and papilloma in rats induced by intratracheal injections of extract from particulate air pollutants.

We investigated the effect of intratracheal injections of an extract of suspended particulate matter (SPM) obtained from the urban ambient air of Tokyo, upon the development of proliferative lesions of pulmonary endocrine cells (PECs) in the rat. We also examined the modification effects of nitrogen dioxide, sulfur dioxide, or both of them on the PEC lesions. Male F344 rats were divided into six experimental groups of 5 animals each. Twenty animals were treated with intratracheal instillations of SPM admixed with carbon once a week for 4 weeks with or without additional gaseous exposure (6 ppm nitrogen dioxide or 4 ppm sulfur dioxide) 16 hrs a day for 11 months. Five animals were given intratracheal injections of carbon suspended in saline and the other five were untreated. The subcardiac lobes of the right lung were fixed with 4% paraformaldehyde, and embedded in paraffin. PEC hyperplasias and papillomas were counted in 200 serial sections, 4 microns thick. The average incidences of PEC hyperplasia in the untreated animals and in those treated with carbon were 194 and 200/cm3, respectively. The average incidences of PEC hyperplasia in the animals exposed to SPM tar only, SPM tar plus nitrogen dioxide and sulfur dioxide, SPM tar with nitrogen dioxide and SPM tar with sulfur dioxide were 376, 378, 372 and 349/cm3, respectively. These were significantly higher than the levels of the control animals, and additional gaseous stimuli had no effect on the incidence of PEC hyperplasia. Besides PEC hyperplasia, a few PEC papillomas were found in the animals treated with SPM tar, regardless of gaseous exposure, but in the control animals no papilloma was evident. Thus, compounds in airborne particulates are considered to be responsible for the development of PEC hyperplasias and papillomas.

APUD Cells↗

Airborne environmental pollutant concentration and hospital epistaxis presentation: a 5-year review.

To investigate the hypothesized relationship between various daily atmospheric pollutant concentrations and hospital epistaxis presentation. A retrospective analysis of all presentations of non-traumatic epistaxis to our institution was performed, and the results were cross-referenced with London air quality data supplied by the National Air Quality Data Archive at the National Environmental Technology Centre (NETCEN) at the multi-centre tertiary referral ENT Department. An analysis of epistaxis presentation to St George's Hospital during the 5-year period January 1997-2002 was made from the patient administration system and accident and emergency records. The study includes 1373 emergency patients after traumatic and iatrogenic epistaxis were excluded. Factors measured were atmospheric ozone (O(3)), carbon monoxide (CO), sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)) and particulate matter less than 10 mum in diameter (PM(10)). Hospital epistaxis presentation and atmospheric pollutant concentration were documented for each day of the 5-year period, weekly change in both parameters was recorded and statistical analysis was performed. The statistical methods used are linear correlation using Pearson's coefficient. Increased hospital epistaxis presentation was strongly associated with increased concentration of airborne particulate matter (r = 0.289, P < 0.001; significant if P < 0.05) and less strongly associated with increased concentrations of atmospheric O(3) (r = 0.150, P = 0.019; significant if P < 0.05). There was no association between epistaxis attendance and atmospheric concentrations of CO, NO(2) and SO(2) in this study. The concentrations of local airborne particulate matter and atmospheric O(3) in the days preceding hospital attendance for epistaxis are relevant when considering the associations of the episode. This further increases understanding of the pathophysiology of spontaneous epistaxis.

Air↗

Air pollution, temperature, and regional differences in lung cancer mortality in Japan.

In this study, the authors investigated regional differences in lung cancer mortality in Japan, and, based on data acquired between 1970 and 1990 for 47 Japanese prefectures, estimated the relationship between regional lung cancer mortality and air pollution and/or temperature. Investigators used data for nitrogen dioxide, sulfur dioxide, motor vehicle density, tobacco expenditure, and temperature as independent variables for age-adjusted lung cancer death rates. The age-adjusted lung cancer death rates were higher in the southern geographical block of Japan (i.e., approximately 1.2-fold in males and 1.1-fold in females) and in the northern block (approximately 1.2-fold in males) than in the central block. The regional differences in the age-adjusted lung cancer death rates were explained by nitrogen dioxide and temperature. Temperature caused a greater effect (regression coefficients) of nitrogen dioxide on the age-adjusted lung cancer death rates than did nitrogen dioxide alone in the southern block (i.e., approximately 1.3-fold in males and 1.2-fold in females). These results provide the first evidence of a possible synergistic interaction between air pollution and high temperature on lung cancer mortality.

Air Pollution↗

Ambient air pollution and asthma exacerbations in children: an eight-city analysis.

The authors investigated the relation between ambient concentrations of five of the Environmental Protection Agency's criteria pollutants and asthma exacerbations (daily symptoms and use of rescue inhalers) among 990 children in eight North American cities during the 22-month prerandomization phase (November 1993-September 1995) of the Childhood Asthma Management Program. Short-term effects of carbon monoxide, nitrogen dioxide, particulate matter less than 10 mum in aerodynamic diameter (PM10), sulfur dioxide, and warm-season ozone were examined in both one-pollutant and two-pollutant models, using lags of up to 2 days. Lags in carbon monoxide and nitrogen dioxide were positively associated with both measures of asthma exacerbation, and the 3-day moving sum of sulfur dioxide levels was marginally related to asthma symptoms. PM10 and ozone were unrelated to exacerbations. The strongest effects tended to be seen with 2-day lags, where a 1-parts-per-million change in carbon monoxide and a 20-parts-per-billion change in nitrogen dioxide were associated with symptom odds ratios of 1.08 (95% confidence interval (CI): 1.02, 1.15) and 1.09 (95% CI: 1.03, 1.15), respectively, and with rate ratios for rescue inhaler use of 1.06 (95% CI: 1.01, 1.10) and 1.05 (95% CI: 1.01, 1.09), respectively. The authors believe that the observed carbon monoxide and nitrogen dioxide associations can probably be attributed to mobile-source emissions, though more research is required.

Air Pollutants↗

Nitric oxide supplied from a 10% source provides inhaled therapy without lowering inspired oxygen fraction.

The authors designed a low-deadspace system to deliver inhaled nitric oxide from a high-concentration (10%) source. Nitric oxide, nitrogen dioxide, and O2 concentrations were compared under simulated inhaled nitric oxide therapy (in vitro) from low (0.08%, 800 ppm) and high (10%, 100,000 ppm) sources of nitric oxide in nitrogen. O2 concentrations remained above 99% and nitrogen dioxide below 3 ppm for nitric oxide delivered at dosages up to 180 ppm from the 10% source. An acute toxicity trial (in vivo) was also performed in nine rabbits mechanically ventilated with 100% O2 for four hours. Six rabbits received 80 ppm nitric oxide from a 10% source and three control rabbits received only O2. Nitric oxide, nitrogen dioxide, and O2 concentrations were monitored in the ventilator circuit. Methemoglobin, arterial blood gases, arterial blood pressure, and heart rate were sampled every hour. At the 80-ppm nitric oxide dose, an average of 1.1 +/- 0.2 ppm of nitrogen dioxide was produced within the ventilator circuit. Arterial methemoglobin in rabbits that received nitric oxide rose by 0.5% from baseline, compared with a 0.2% rise for controls (p = 0.001). The authors conclude that inhaled nitric oxide therapy can be provided from a high-concentration source. Because this system does not reduce inspired O2 fraction, it may be more appropriate than low-source-concentration nitric oxide delivery systems for testing the efficacy of inhaled nitric oxide as an adjunct to optimal conventional medical therapy.

Animals↗

Bactericidal activity of peroxynitrite.

Peroxynitrite is a strong oxidant formed by macrophages and potentially by other cells that produce nitric oxide and superoxide. Peroxynitrite was highly bactericidal, killing Escherichia coli in direct proportion to its concentration with an LD50 of 250 microM at 37 degrees C in potassium phosphate, pH 7.4. The apparent bactericidal activity of a given concentration peroxynitrite at acidic pH was less than that at neutral and alkaline pH. However, after taking the rapid pH-dependent decomposition of peroxynitrite into account, the rate of the killing was not significantly different at pH 5 compared to pH 7.4. Metal chelators did not decrease peroxynitrite-mediated killing, indicating that exogenous transition metals were not required for toxicity. The hydroxyl radical scavengers mannitol, ethanol, and benzoate did not significantly affect toxicity while dimethyl sulfoxide enhanced peroxynitrite-mediated killing. Dimethyl sulfoxide is a more efficient hydroxyl radical scavenger than the other three scavengers and increased the formation of nitrogen dioxide from peroxynitrite. In the presence of 100 mM dimethyl sulfoxide, 60.0 +/- 0.3 microM nitrogen dioxide was formed from 250 microM peroxynitrite as compared to 2.0 +/- 0.1 microM in buffer alone. Thus, formation of nitrogen dioxide may have enhanced the toxicity of peroxynitrite decomposing in the presence of dimethyl sulfoxide.

Anti-Bacterial Agents↗

Nitration and photonitration of naphthalene in aqueous systems.

The nitration of naphthalene was studied in aqueous solution to gain insight into the processes leading to the nitration of aromatic compounds in atmospheric hydrometeors. Reactants used were nitric acid, nitrogen dioxide and peroxynitrous acid in the dark, nitrate, and nitrite/nitrous acid under illumination. Naphthalene nitration can lead to two possible isomers, 1- and 2-nitronaphthalene. The former nitrocompound preferentially forms upon electrophilic processes and in the presence of nitrogen dioxide. Electrophilic nitration of naphthalene takes place in the presence of concentrated nitric acid, but nitration with nitric acid and oxidants (charge-transfer nitration) occurs under much milder conditions than with nitric acid alone. Charge-transfer nitration may have some environmental significance in particular cases, e.g. in acidic aerosols in the presence of HNO3 and oxidants. Nitrogen dioxide is thought to have a role in PAH nitration in the Antarctic particulate matter. In previous papers we have found that nitration induced by peroxynitrous acid, HOONO, can follow two pathways, the former electrophilic (leading for instance to the formation of nitrophenols from phenol) and the latter probably involving HOONO itself (accounting for the formation of nitrobenzene from benzene). In the case of naphthalene and HOONO the electrophilic pathway mainly leads to 1-nitronaphthalene, while the other one preferentially yields 2-nitronaphthalene. The nitration of naphthalene in the presence of nitrite/nitrous acid under irradiation leads to both nitroisomers in similar ratios, and the process is not inhibited by hydroxyl scavengers. This excludes nitrogen dioxide as reactive species for nitration and marks a difference with phenol photonitration and a similarity with the behavior of benzene under comparable conditions. Nitrite photochemistry (and nitrite-induced photonitration as well) is expected to be relevant in fog and cloudwater in polluted areas. An important difference with the gas-phase nitration is that the radicals OH and NO3 are unlikely to play a relevant role in the nitration of naphthalene in aqueous solution.

Benzene↗