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Biomedical subjects

R Vincent

Publications and source records attributed to R Vincent.

At least 37 records · Page 2Linked to original sources
PubMed2000

Suppression of rat and mouse lymphocyte function by urban air particulates (Ottawa dust) is reversed by N-acetylcysteine.

Epidemiology studies have demonstrated increased pulmonary morbidity such as allergy and infection with episodes of high particulate air pollution (size range 0.1-10 microm diameter, PM10), but the mechanism(s) for this association is not yet well defined. The present study was undertaken to evaluate the effects of EHC-93 urban particles (Ottawa dust) on immune functions of peripheral blood mononuclear cells (PBMCs) and splenocytes from male Fischer 344 rats and C57Bl/6 mice. Immune function endpoints evaluated included cell viability, lymphocyte blastogenesis stimulated by T-cell mitogen (concanavalin A, Con A) or B-cell mitogens [lipopolysaccharide (LPS) or LPS/dextran sulfate], intracellular Ca2+ concentration, interleukin 2 (IL-2) production, and expression of receptors for transferrin (TfR) and IL-2 (IL-2R). In addition, the effect of N-acetylcysteine (NAC), an antioxidant, on the toxicity of EHC-93 particles was evaluated. Total EHC-93 particles, water leachate of EHC-93, and washed EHC-93 suppressed proliferation of PBMCs and splenocytes to T- and B-cell mitogens. Treatment of splenocytes with EHC-93 particles did not alter intracellular Ca2+ concentration or mitogen-induced expression of TfR and IL-2R expression, but increased IL-2 production assayed by enzyme-linked immunosorbent assay (ELISA). In spite of an increase in IL-2 production, exogenous IL-2 when added to cultures was able to reverse the suppression of Con A-induced lymphocyte proliferation by EHC-93 particles. Furthermore, the suppressive effect of EHC-93 particles on mitogen-induced lymphocyte proliferation was completely abolished by addition of the antioxidant NAC to cultures, suggesting a possible role of oxidative factors for the toxicity of EHC-93 particles.

Acetylcysteine↗
PubMed2000

Association between particulate- and gas-phase components of urban air pollution and daily mortality in eight Canadian cities.

Although some consensus has emerged among the scientific and regulatory communities that the urban ambient atmospheric mix of combustion related pollutants is a determinant of population health, the relative toxicity of the chemical and physical components of this complex mixture remains unclear. Daily mortality rates and concurrent data on size-fractionated particulate mass and gaseous pollutants were obtained in eight of Canada's largest cities from 1986 to 1996 inclusive in order to examine the relative toxicity of the components of the mixture of ambient air pollutants to which Canadians are exposed. Positive and statistically significant associations were observed between daily variations in both gas- and particulate-phase pollution and daily fluctuations in mortality rates. The association between air pollution and mortality could not be explained by temporal variation in either mortality rates or weather factors. Fine particulate mass (less than 2.5 microns in average aerometric diameter) was a stronger predictor of mortality than coarse mass (between 2.5 and 10 microns). Size-fractionated particulate mass explained 28% of the total health effect of the mixture, with the remaining effects accounted for by the gases. Forty-seven elemental concentrations were obtained for the fine and coarse fraction using nondestructive x-ray fluorescence techniques. Sulfate concentrations were obtained by ion chromatography. Sulfate ion, iron, nickel, and zinc from the fine fraction were most strongly associated with mortality. The total effect of these four components was greater than that for fine mass alone, suggesting that the characteristics of the complex chemical mixture in the fine fraction may be a better predictor of mortality than mass alone. However, the variation in the effects of the constituents of the fine fraction between cities was greater than the variation in the mass effect, implying that there are additional toxic components of fine particulate matter not examined in this study whose concentrations and effects vary between locations. One of these components, carbon, represents half the mass of fine particulate matter. We recommend that measurements of elemental and organic carbon be undertaken in Canadian urban environments to examine their potential effects on human health.

Air Pollutants↗
PubMed2000

Patients' interpretation of symptoms as a cause of delay in reaching hospital during acute myocardial infarction.

OBJECTIVE: To examine whether the association between expected symptoms of acute myocardial infarction and actual symptoms predicted delay in reaching hospital and help seeking behaviour. DESIGN: During hospital convalescence, participants completed a structured interview designed to measure symptom experience and help seeking behaviour following the onset of symptoms of acute myocardial infarction. PATIENTS: 88 patients admitted to hospital with their first myocardial infarction MAIN OUTCOME MEASURES: Delay in reaching hospital from onset of worst symptoms, obtained from ambulance and hospital records. RESULTS: The most common symptoms expected by patients with myocardial infarction were central chest pain (76%), radiating arm or shoulder pain (34%), and collapse (26%). The most common symptoms experienced were sweats or feeling feverish (78%), chest pain (64%), and arm, shoulder, or radiating pain (66%). A mismatch between symptoms experienced and those expected occurred in 58% of patients, and was associated with delay. Patients who experienced a mismatch between expectation and actual symptoms also were more likely to have a third party decide to call for help. CONCLUSIONS: The experience and interpretation of symptoms is an important source of delay and help seeking following onset of myocardial infarction symptoms.

Aged↗
PubMed2000

Occupational exposure to carcinogens in the European Union.

OBJECTIVES: To construct a computer assisted information system for the estimation of the numbers of workers exposed to established and suspected human carcinogens in the member states of the European Union (EU). METHODS: A database called CAREX (carcinogen exposure) was designed to provide selected exposure data and documented estimates of the number of workers exposed to carcinogens by country, carcinogen, and industry. CAREX includes data on agents evaluated by the International Agency for Research on Cancer (IARC) (all agents in groups 1 and 2A as of February 1995, and selected agents in group 2B) and on ionising radiation, displayed across the 55 industrial classes. The 1990-3 occupational exposure was estimated in two phases. Firstly, estimates were generated by the CAREX system on the basis of national labour force data and exposure prevalence estimates from two reference countries (Finland and the United States) which had the most comprehensive data available on exposures to these agents. For selected countries, these estimates were then refined by national experts in view of the perceived exposure patterns in their own countries compared with those of the reference countries. RESULTS: About 32 million workers (23% of those employed) in the EU were exposed to agents covered by CAREX. At least 22 million workers were exposed to IARC group 1 carcinogens. The exposed workers had altogether 42 million exposures (1.3 mean exposures for each exposed worker). The most common exposures were solar radiation (9.1 million workers exposed at least 75% of working time), environmental tobacco smoke (7.5 million workers exposed at least 75% of working time), crystalline silica (3.2 million exposed), diesel exhaust (3.0 million), radon (2.7 million), and wood dust (2.6 million). CONCLUSION: These preliminary estimates indicate that in the early 1990s, a substantial proportion of workers in the EU were exposed to carcinogens.

Carcinogens↗
PubMed2000

Phagocytosis of particulate air pollutants by human alveolar macrophages stimulates the bone marrow.

Epidemiologic studies have shown an association between the level of ambient particulate matter < 10 microm (PM(10)) and cardiopulmonary mortality. We have shown that exposure of rabbits to PM(10) stimulates the bone marrow. In this study, we determined whether human alveolar macrophages (AMs) that phagocytose atmospheric PM(10) produce mediators capable of stimulating the bone marrow. AMs incubated with PM(10) for 24 h produced tumor necrosis factor-alpha in a dose-dependent manner (86.8 +/- 53.29 pg/ml with medium alone; 1,087.2 +/- 257.3 pg/ml with 0.1 mg/ml of PM(10); P < 0.02). Instillation of the supernatants from AMs incubated with 0.1 mg/ml of PM(10) into the lungs of rabbits (n = 6) increased circulating polymorphonuclear leukocyte (PMN) and band cell counts as well as shortened the PMN transit time through the bone marrow (87.9 +/- 3.3 h) compared with unstimulated human AMs (104.9 +/- 2.4 h; P < 0.01; n = 5 rabbits). The supernatants from rabbit AMs incubated with 0.1 mg/ml of PM(10) (n = 4 rabbits) caused a similar shortening in the PMN transit time through the bone marrow (91.5 +/- 1.6 h) compared with human AMs. We conclude that mediators released from AMs after phagocytosis of PM(10) induce a systemic inflammatory response that includes stimulation of the bone marrow.

Air Pollutants↗
PubMed1999

Pulmonary toxicity of an atmospheric particulate sample is due to the soluble fraction.

Adverse health effects have been associated with the inhalation of a variety of atmospheric particles. The potential toxicity of a recently collected urban air particulate sample (EHC-93, mean diameter < 1 microm) was assessed after instilling 1 mg to mouse lung. A soluble fraction (15% of total) and an insoluble fraction of the original dust were also instilled at 1 and 0.15 mg doses and the lung reaction was followed for up to 8 weeks. The complete dust sample induced an inflammatory response in the first week with increased cell numbers and protein levels in lavage fluid. There was also ultrastructural evidence of epithelial necrosis followed by increased thymidine labeling during repair. The insoluble fraction induced only mild inflammation with no evidence of cell injury or repair at either dose. The soluble fraction produced similar early inflammatory changes but also produced the greatest lung injury. Type 1 cell necrosis was observed, followed by increased tritiated thymidine uptake mainly by Type 2 epithelial cells. This was found after 0.15 mg soluble fraction and was greatly increased in the 1.0 mg group, which subsequently developed fibrosis. The results indicate that while all particle samples induce some inflammation, the lung toxicity produced by the total dust sample EHC-93 can be accounted for by the reaction to its 15% soluble component. This suggests that the pulmonary response and cell injury following exposure to this urban dust is related to soluble material, probably metal ions, rather than to the number or composition of the insoluble particles.

Air Pollutants↗
PubMed1999

Evidence for differences in MT2 cell tropism according to genetic subtypes of HIV-1: syncytium-inducing variants seem rare among subtype C HIV-1 viruses.

Non-syncytium-inducing (NSI) variants seem to be more readily transmitted than syncytium-inducing (SI) variants, and the switch from NSI to SI during HIV-1 infection seems to be a key determinant to the evolution of AIDS. We investigated eventual differences in the SI capacity on MT-2 cells according to genetic subtypes of HIV-1 and correlated this observations with CD4 counts and duration of HIV infection. In total, 86 patients, most with known date of HIV contamination and infected with different genetic subtypes, have been studied: 11 subtype A, 46 subtype B, 22 subtype C, and 7 subtype E. Multivariate analysis used a Cox's proportional hazards regression. The number and percentage of patients infected with an SI strain were as follows: 3 of 11 (27%) for subtype A, 15 of 46 (33%) for subtype B, 0 of 22 (0%) for subtype C, and 5 of 7 (71%) for subtype E. After adjustment for time after seroconversion and CD4 counts, significantly fewer SI variants were observed in patients infected with subtype C (p < .002) and it was found that subjects infected with subtype E had a higher risk of being infected with an SI strain (rate ratio [RR] = 12.39%; 95% confidence interval [CI] 1.55-98.67; p < .001). Most of the subtype E-infected patients from our study switched from an NSI to SI phenotype early after seroconversion (<4 years). To predict the in vitro presence of SI variants, we scanned V3-loop sequences for mutations at positions 11 and/or 25. Overall, 54 of 55 (98.2%) NSI strains in vitro were predicted NSI, and only 4 of 12 (33.3%) of SI viruses were predicted SI. For patients in whom a switch from an NSI to an SI virus was observed, the SI phenotype could be detected earlier in vitro than by the corresponding V3-loop sequence. No SI strains were observed among patients infected with subtype C; however, longer follow-up is needed to see whether the appearance of SI variants in subtype E or the absence of SI variants in subtype C-infected patients is also associated respectively with a faster or slower progression to AIDS as described for subtype B.

Amino Acid Sequence↗
PubMed1999

Vascular surgical society of great britain and ireland: perioperative renal function following endovascular repair of abdominal aortic aneurysm with suprarenal and infrarenal stents

BACKGROUND: Endovascular repair (EVR) of abdominal aortic aneurysm (AAA) is feasible for selected patients. Placing an uncovered stent across the origins of the renal arteries may improve fixation and seal of the proximal end of the stent-graft. However, this has potential for problems (e.g. renal artery stenosis or microembolization). This study aimed to evaluate the short-term effect of a suprarenal stent on the function of the individual kidney. METHODS: In 30 patients undergoing EVR for AAA, renal function was assessed before and after operation by 99mTc-radiolabelled diethylenetriamine penta-acetate radionuclide renography and daily measurement of serum creatinine levels. Eleven patients had infrarenal stent-grafts using an aorta uni-iliac system (group 1); 19 patients had the device with an uncovered suprarenal stent (modified Gianturco Z stent), ten of which were aorta uni-iliac and nine bifurcated systems (group 2). Individual kidney function was expressed as the whole kidney transit time (WKTT). In addition, glomerular filtration rate (GFR) was measured from serial blood samples following renography. RESULTS: [Table: see text] CONCLUSION: No result reached statistical significance. Placing an uncovered stent over the origins of the renal arteries does not appear to impair kidney function in the short term.

Journal Article↗
PubMed1999

Cell injury and interstitial inflammation in rat lung after inhalation of ozone and urban particulates.

Coexposure of the lung to urban dust along with ozone appears to potentiate ozone-induced injury. This conclusion was derived from whole-lung studies involving tissue and lavaged cells, but we now speculate that the injury and inflammatory response at the main site of reactivity, the bronchoalveolar duct region, is underestimated by such whole-lung studies. We exposed rats to ozone at 0.8 ppm and urban particulates (EHC93) at 50 mg/m3 for 4 h. Animals were killed 33 h later with tritiated thymidine (3HT) injected 1.5 h before death. Lungs were fixed by vascular perfusion to avoid disturbing any epithelial cell changes or local inflammation and edema in the air spaces. Tissue was embedded from central and peripheral areas of the lung, then counts of labeled cells, polymorphonuclear leukocytes (PMN), and macrophages (MAC) were made separately on methacrylate sections. The results showed that epithelial cell injury and regeneration (% of 3HT-labeled cells) was greatest in the ozone plus dust group, and was three times higher in periductal areas than in whole-lung counts. Although some increase in inflammatory cells in the air spaces was found in the coexposure group, much higher numbers of PMN and MAC were counted in the lung tissue compartment, and counts were significantly higher than those found after ozone or dust alone. Values from the latter groups were also higher than those from air controls or samples of distal lung taken from any inhalation group. The results demonstrate that inhalation of an urban dust at a level that causes few lung effects when inhaled alone can potentiate ozone toxicity, particularly in the vicinity of the alveolar duct, where the accumulation of interstitial inflammatory cells may be an important factor in the development of any subsequent pathologic changes.

Air Pollutants↗
PubMed1999

Population effects of the bombing of Oklahoma City.

BACKGROUND AND PURPOSE: The explosion at the Murrah Federal Building in Oklahoma City on April 19, 1995, affected many members of the community as well as direct victims. Our goal was to measure the exposure and effects among the general population. METHODS: We conducted surveys of the Oklahoma City metropolitan area and a control area to measure exposure and impact, primarily stress and psychological distress. RESULTS: Of the adults in the Oklahoma City MSA, 61.5 percent (58.5 percent to 64.5 percent with 95 percent confidence) reported experiencing at least one direct result of the bombing. In population terms, about 433 thousand adults (between 412 thousand and 457 thousand, with 95 percent confidence) were exposed to one or more of the consequences of the bombing. Oklahomans reported higher rates (about double) of increased alcohol use, smoking more or starting smoking. They reported more stress (about double), psychological distress (about double), post-traumatic stress-disorder components, and intrusive thoughts (double) related to the bombing than in the control area. Oklahomans also reported higher rates of seeking help for their stress or taking steps to reduce stress. The differences persisted into 1996, more than a year after the bombing. CONCLUSION: The exposure to the bombing was widespread, including more than half the adults in the metropolitan area surrounding Oklahoma City. The psychological effects were high and, while decreasing, persisted more than a year after the bombing. Primary care practitioners should screen their patients, who may normally not be considered victims, for exposure to the effects of a terrorist disaster for an extended period of time.

Adult↗
PubMed1999

Malleus ankylosis: a clinical, audiometric, histologic, and surgical study of 123 cases.

OBJECTIVE: Malleus ankylosis is a cause of conductive hearing loss that can be difficult to assess, particularly in association with otosclerotic stapes fixation. The aim of this study is to seek the clinical and audiometrical features unique to this pathology. STUDY DESIGN: The study design was a review of malleus ankylosis cases and an analysis of functional results after ossiculoplasty. SETTING: The study was performed at Jean Causse Clinic in France. PATIENTS: The authors reviewed a series of 123 ears in 112 patients who underwent surgery for incudo-mallear ankylosis from January 1991 to September 1997. INTERVENTION: The surgical technique depends on the type of pathology encountered. In case of associated stapedial fixation, a stapedotomy with vein graft interposition and reconstruction with a total prosthesis will be performed during a same step. MAIN OUTCOME MEASURES: Clinical evaluation, preoperative and postoperative audiometrical evaluation, operative findings, histologic examination, and postoperative functional results. RESULTS: In our series, a postoperative air-bone gap smaller than 10 dB was obtained in 77% of cases. These results confirm the possibility of managing both pathologies in a single surgical step. CONCLUSION: Incudo-mallear ankylosis remains an unusual pathology but should be systematically assessed during surgery and preferably after separation of the incudo-stapedial joint. A preoperative diagnosis is difficult to ascertain; some audiometrical features allow a suspicion. In this series, it is shown that otosclerosis can be responsible for ankylosis as seems to be confirmed by the two cases presented in this study.

Adolescent↗
PubMed1999

Barriers to optimum management of heart failure by general practitioners.

BACKGROUND: Published research offers clear pointers to the management of heart failure; however, the evidence for implementation into practice is sub-optimal. AIM: To identify the salient barriers to adopting evidence-based management of heart failure in the community. METHOD: Structured interviews were used to elicit the views of a stratified sample of 100 general practitioners (GPs) about the diagnosis and treatment of heart failure. Responses to three heart failure case scenarios provided an indication of the degree to which GPs' knowledge of heart failure and trial results might be applied to diagnosis and treatment intentions. RESULTS: Participants were generally well aware of clinical trials that showed that prognosis could be improved by treatment, but trial results appeared to have little influence on treatment intentions in the three case scenarios. The major barriers to optimum management were the difficulties of differential diagnosis and the perceived properties of angiotensin-converting enzyme inhibitors (ACE-I) relative to diuretics. In the case scenarios, less than 30% reported that they would undertake basic investigations, such as chest X-ray or haemoglobin, or prescribe ACE-I. Over 70% perceived diuretics to be a useful diagnostic tool. The most frequent reasons for not prescribing ACE-I were the perceived inconvenience and risks of adverse effects (41%) and the view that most patients can be managed successfully on diuretics alone (27%). Over two-thirds of the sample were dissatisfied with the quality of information accompanying heart failure patients discharged from hospital. CONCLUSION: Facilitating evidence-based management of heart failure in the community requires further support for GPs in the form of additional training in the diagnosis of heart failure and the optimum use of both ACE-I and diuretics, and by improved communication between GPs and hospital doctors on a case-by-case basis.

Aged↗
PubMed1998

The signal averaged P wave in atrioventricular block--evidence for abnormal atrial conduction?

The incidence of atrial fibrillation in patients with atrioventricular block (AVB) appears increased over that for the unpaced population even if atrioventricular synchrony is maintained by dual chamber pacing. To assess whether atrial fibrillation in these patients might be due to concurrent abnormality in atrial activation we performed signal averaged P wave (SAPW) recordings in 15 patients with dual chamber pacemakers implanted for AVB and compared the results to those from 21 unpaced controls. The median (range) age was 69 (53-89) years for patients and 60 (51-78) years for controls. Eleven patients and 12 controls were male. All patients were pacing in VDD mode at the time of study. SAPW recordings were obtained using our previously reported selective P wave averaging system. We measured P wave duration after high pass filtering at 40 Hz, the rate of change of P wave voltage over time (spatial velocity) and low and high frequency spectral energy after Fourier transformation of the P wave signal. We found increased P wave duration, mean spatial velocity and lower frequency energy in patients with AVB compared to controls [duration, 144 (5) vs. 134 (2) ms, p<0.05; mean spatial velocity, 5.6 (0.4) vs. 4.6 (0.1) mV/s, p<0.05; energy 20-150 Hz, 57.4 (8.2) vs. 36.3 (2.8) muV2.s, p<0.01. All values mean (SEM)]. These results suggest that the increased incidence of atrial fibrillation in patients paced for AVB may be related to intrinsic abnormalities of atrial activation and not solely to the pacing mode. Ensuring sequential atrioventricular pacing in these patients may not completely abolish the increased incidence of atrial fibrillation.

Aged↗
PubMed1998

Association of genetic polymorphisms in the ACE, ApoE, and TGF beta genes with early onset ischemic heart disease.

BACKGROUND: The genetic factors that contribute to ischemic heart disease (IHD) are poorly understood, and it is likely that multiple genes acting independently or synergistically contribute to the risk of IHD and outcome. The genes for angiotensin-converting enzyme (ACE) and apolipoprotein E (ApoE) have been implicated independently in the risk of IHD. HYPOTHESIS: This study examined whether genetic polymorphisms in the ACE and ApoE genes are associated with early onset IHD. Polymorphisms in a third gene, transforming growth factor beta 2 (TGF beta 2), with a known role in wound repair and cardiac development, are also examined with respect to early onset IHD. METHODS: In all, 101 patients with IHD and onset of disease before 55 years for men and 60 years for women, and 100 controls with angiographically confirmed normal coronary arteries were recruited for this study. The ACE, ApoE, and TGF beta 2 genotypes were determined by polymerase chain reaction amplification or Southern blotting and were compared with the patient's clinical and family histories. RESULTS AND CONCLUSION: The frequency of the ACE D allele was significantly lower in the patient group (0.475) than in the control group (0.59, p = 0.03), which was attributed to a reduction in the number of patients with the DD genotype (patients: 24% DD, controls: 33% DD). Sudden cardiac death was also associated with the DD genotype. These data are consistent with the ACE D allele contributing to a fatal outcome. No association between the DD genotype and risk of myocardial infarction, presenting age, extent of vessel disease, family history, hypertension, or hypercholesterolemia was seen. Analysis of the ApoE genotype showed no association with early onset IHD. There was no evidence for a synergistic effect between the ACE and ApoE genotypes on the risk of early onset IHD. A polymorphism in the TGF beta 2 gene was rare and not associated with early onset IHD.

Adult↗
PubMed1998

Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice.

Generation of free radicals upon reperfusion has been cited as one of the major causes of ischaemia/reperfusion injury. The following series of experiments was designed to study the effect of manganese superoxide dismutase (MnSOD) overexpression in transgenic mice on ischemia/reperfusion injury. A species of 1.4 kb human MnSOD mRNA was expressed, and a 325% increase in MnSOD activity was detected in the hearts of transgenic mice with no changes in the other antioxidant enzymes or heat shock proteins. Immunocytochemical study indicated an increased labeling of MnSOD mainly in the heart mitochondria of the transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed as heart rate x left ventricular developed pressure, was 52 +/- 4% in the transgenic hearts as compared to 31 +/- 4% in the non-transgenic hearts. This protection was accompanied by a significant decrease in lactate dehydrogenase release from the transgenic hearts. Overexpression of MnSOD limited the infarct size in vivo in a left coronary artery ligation model. Our results demonstrate that overexpression of MnSOD renders the heart more resistant to ischemia/reperfusion injury.

Animals↗
PubMed1998

Oklahoma City: disaster challenges mental health and medical administrators.

Mental health and medical administrators responded to the Oklahoma City bombing with cooperative and overlapping efforts to meet community needs in the wake of terrorism. The major agencies assisted in the immediate rescue response, organized crisis hotlines, prepared mental health professionals to counsel bereaved families and victims, organized debriefing of rescuers, assessed mental health needs of local school children, planned for longer term treatment, and coordinated research efforts to learn from the disaster. Implications to mental health administrators responding to significant acts of terrorism are discussed.

Adult↗
PubMed1998

Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1.

We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air appear related to paracrine/endocrine disruption mechanisms.

Animals↗