Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ELF”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
PubMed1991

Immunoglobulin and antibody levels in bronchoalveolar lavage fluid from symptomatic and asymptomatic pigeon breeders.

Twenty-one symptomatic subjects with pigeon breeders' lung (PBL) and 10 asymptomatic pigeon breeders, with a similar exposure to pigeon antigens, underwent bronchoalveolar lavage. Total IgG, IgM and IgA in lavage fluid were determined as were specific antibody levels against antigens in pigeon serum and droppings. Results were converted to levels in epithelial lining fluid (ELF) using lavage and serum urea ratios. It was found that symptomatics represent a group that is hyperreactive to pigeon antigens compared with the asymptomatic group with significantly higher IgG, IgM, IgA levels as well as specific antibody levels against pigeon serum and droppings. Paired serum and ELF samples from 12 symptomatic subjects showed significantly elevated IgG, IgM and IgA levels in ELF compared with serum when values were expressed in terms of albumin. This strongly supports the concept of local production of immunoglobulins within the lung after inhaling immunogens as opposed to their diffusion from the vasculature. Results for IgA indicate that any putative protective role for this immunoglobulin is not valid in relation to the prevention of extrinsic allergic alveolitis. Analysis of smoking habits, lung immunoglobulins and response to inhalation challenge confirm the negative influence of smoking on total and functional lung immunoglobulins; however, levels in the ELF of ex-smokers suggest that the effect of smoking is not permanent. Smoking did not prevent responses to inhalation challenge.

Allergens↗
PubMed2007

Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

Aged↗
PubMed2005

Influence of exposure to electromagnetic field on the cardiovascular system.

1 We examined whether extremely low frequency electromagnetic fields (ELF-EMF) affect the basal level of cardiovascular parameters and influence of drugs acting on the sympathetic nervous system. 2 Male rats were exposed to sham control and EMF (60 Hz, 20 G) for 1 (MF-1) or 5 days (MF-5). We evaluated the alterations of blood pressure (BP), pulse pressure (PP), heart rate (HR), and the PR interval, QRS interval and QT interval on the electrocardiogram and dysrhythmic ratio in basal level and dysrhythmia induced by beta-adrenoceptor agonists. 3 In terms of the basal levels, there were no statistically significant differences among control, MF-1 and MF-5 in PR interval, QRS interval, mean BP, HR and PP. However, the QT interval, representing ventricular repolarization, was significantly reduced by MF-1 (P < 0.05). 4 (-)-Dobutamine (beta1-adrenoceptor-selective agonist)-induced tachycardia was significantly suppressed by ELF-EMF exposure in MF-1 for the increase in HR (DeltaHR), the decrease in QRS interval (DeltaQRS) and the decrease in QT (DeltaQT) interval. Adrenaline (nonselective beta-receptor agonist)-induced dysrhythmia was also significantly suppressed by ELF-EMF in MF-1 for the number of missing beats, the dysrhythmic ratio, and the increase in BP and PP. 5 These results indicated that 1-day exposure to ELF-EMF (60 Hz, 20 G) could suppress the increase in HR by affecting ventricular repolarization and may have a down-regulatory effect on responses of the cardiovascular system induced by sympathetic agonists.

Animals↗
PubMed2002

Antioxidant supplementation and pulmonary function at rest and exercise.

Antioxidants have been implicated in the reduction and prevention of oxidative stress during exercise. We hypothesised that a dietary supplement containing a mixture of natural antioxidants together with vitamins E, C and selenium, given for 4 weeks, would increase the systemic and pulmonary antioxidant capacity leading to a reduction in markers of oxidative damage and an improvement in pulmonary function during exercise. In 6 healthy horses studied, the antioxidant supplement significantly increased plasma concentrations of ascorbic acid (from mean +/- s.d. 16 +/- 7 to 23 +/- 4 micromol/l; P = 0.007) and alpha-tocopherol (from 10 +/- 3 to 14 +/- 3 micromol/l; P = 0.02) and increased the bronchoalveolar lavage pulmonary epithelial lining fluid (ELF) concentration of ascorbic acid compared to a placebo, but not significantly (2.0 +/- 0.9 mmol/l and 1.2 +/- 0.9 mmol/l, respectively; P>0.05). Alpha-tocopherol was not detected in ELF either before or after supplementation or exercise. The mean concentration of malondialdehyde (MDA) in ELF was lower following antioxidant supplementation compared to placebo and control periods, but not significantly. An intermittent exercise test consisting of 2 min at 70, 80 and 90% of the horses' individual maximum oxygen uptake, failed to induce significant systemic or pulmonary oxidative stress (based on the glutathione redox ratio (GRR) and the ascorbic acid redox ratio (ARR)) and lipid peroxidation (based on the concentration of thiobarbituric acid reactive substances in plasma and MDA in ELF) either for placebo or antioxidant treatments. There was a strong correlation between GRR and ARR in the pulmonary epithelial lining fluid (r = 0.89; P<0.0001). In healthy horses on a diet containing adequate levels of antioxidants, additional antioxidant supplementation has no apparent beneficial or detrimental effect on pulmonary function during moderate intensity exercise. The importance of antioxidant supplementation may only become apparent if the diet is deficient in antioxidants, if exercise intensity is higher or more prolonged, or if disease or additional stresses are present.

Animals↗
PubMed1997

Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers.

The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported. Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.

Administration, Oral↗
PubMed1999

Intrapulmonary concentrations of pyrazinamide.

The objective of this study was to compare the steady-state plasma and intrapulmonary concentrations of orally administered pyrazinamide in normal volunteers and subjects with AIDS. Pyrazinamide was administered at 1 g once daily for 5 days to 40 adult volunteers (10 men with AIDS, 10 normal men, 10 women with AIDS, and 10 normal women). Subjects with AIDS and with more than four stools per day were excluded. Blood was obtained prior to administration of the first dose, 2 h after the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. The total number of alveolar cells (AC) was counted in a hemocytometer, and differential cell counting was performed after cytocentrifugation. Pyrazinamide was measured by high-performance liquid chromatography. The presence of AIDS or gender had no significant effect on the concentrations of pyrazinamide in plasma. The concentrations of pyrazinamide in ELF and AC were lower in the subjects with AIDS than in the subjects without AIDS, but the difference was not significant. The concentrations in plasma (mean +/- standard deviation) were 25.1 +/- 7.6 and 21.1 +/- 6.8 microg/ml at 2 and 4 h after the last dose, respectively, and were not significantly different from the concentration (17.4 +/- 16.9 microg/ml) in AC. The concentration of pyrazinamide in ELF was high (431 +/- 220 microg/ml) and was approximately 4 to 40 times the reported MIC for pyrazinamide-susceptible strains of Mycobacterium tuberculosis. The high concentration of pyrazinamide in ELF may contribute in part to the effectiveness of the drug in treating pulmonary tuberculosis.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Single-dose intrapulmonary pharmacokinetics of rifapentine in normal subjects.

The intrapulmonary pharmacokinetics of rifapentine were studied in 30 volunteers who received a single, oral dose of rifapentine (600 mg). Subgroups of five subjects each underwent bronchoscopy and bronchoalveolar lavage (BAL) at timed intervals following drug administration. Drug concentrations, including the concentration of the primary metabolite 25-desacetyl rifapentine, were determined in plasma, BAL fluid, and alveolar cells (AC) by high-pressure liquid chromatography. The concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The concentration-time data were fit to two-compartment (plasma) or one-compartment (AC and ELF) models. The peak concentrations in plasma, ELF, and AC, 26.2, 3. 7, and 5.3 microg/ml, respectively, occurred at 5, 5, and 7 h after drug administration, respectively. The half-lives and areas under the curve for plasma, ELF, and AC were 18.3 h and 520 microg. h/ml, 20.8 h and 111 microg. h/ml, and 13.0 h and 133 microg. h/ml, respectively. Although the intrapulmonary rifapentine concentrations were less than the plasma rifapentine concentrations at all time periods, they remained above the proposed breakpoint for M. tuberculosis (0.5 microg/ml) for the 48-h observation period. These data provide a pharmacokinetic rationale for extended-interval dosing. The optimum dosing regimen for rifapentine will have to be determined by controlled clinical trials.

Adolescent↗
PubMed2000

Effects of AIDS and gender on steady-state plasma and intrapulmonary ethionamide concentrations.

Ethionamide, 250 mg every 12 h for a total of nine doses, was administered to 40 adult volunteers (10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women). Blood was obtained for drug assay prior to administration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Ethionamide was measured in epithelial lining fluid (ELF) and alveolar cells (AC) using a new mass spectrometric method. The presence of AIDS or gender was without significant effect on the concentrations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean +/- standard deviation [SD]) were 0.97 +/- 0.65 and 0.65 +/- 0.35 microg/ml at 2 and 4 h after the last dose, respectively, and both values were significantly greater than the concentration of ethionamide in AC (0.38 +/- 0.47 microg/ml) (P < 0. 05). The concentration of ethionamide was significantly greater in ELF (5.63 +/- 3.8 microg/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible strains of Mycobacterium tuberculosis. For all 40 subjects, the ELF/plasma concentration ratios (mean +/- SD) at 2 and 4 h were 8.7 +/- 11.7 and 9.7 +/- 5.6, respectively. We conclude that the absorption of orally administered ethionamide, as measured in this study, was not affected by gender or the presence of AIDS. Ethionamide concentrations were significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial activity resides in this compartment.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Effects of AIDS and gender on steady-state plasma and intrapulmonary ethambutol concentrations.

Our objective was to study the steady-state plasma and intrapulmonary orally administered ethambutol concentrations in healthy volunteers and subjects with AIDS. Ethambutol (15 mg/kg of body weight) was administered orally once daily to 10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women. The mean (+/-standard deviation [SD]) CD4 cell count for the 20 subjects with AIDS was (350 +/- 169) x 10(6) cells per liter. Blood was obtained for drug assay 2 h after the last dose and at the completion of bronchoalveolar lavage, performed 4 h after the last dose. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) was calculated by the urea dilution method. The total number of alveolar cells (AC) was counted in a hemocytometer, and differential cell counting was performed after cytocentrifugation. Ethambutol was measured by a new, sensitive and specific liquid chromotography-mass spectrometry method. The presence of AIDS, as defined in this study, or gender was without significant effect on the concentrations of ethambutol in plasma at 2 or 4 h or in ELF at 4 h following the last dose. Plasma drug concentrations (mean +/- SD) at 2 and 4 h were 2.1 +/- 1.2 and 2.1 +/- 0.8 microg/ml, respectively, and both values were not significantly different from the concentration of ethambutol in ELF at 4 h (2.2 +/- 1.1 microg/ml). The concentration of ethambutol was significantly greater in AC in all four groups (range, 44.5 +/- 15.6 to 82.0 +/- 39.4 microg/ml) than in ELF or plasma and was approximately 30 to 240 times the reported MIC for ethambutol-susceptible strains of Mycobacterium tuberculosis. The AC ethambutol concentration (mean +/- SD) in the smoking women (97.2 +/- 32.1 microg/ml) was more than twice the concentration in all other nonsmoking subjects (45.2 +/- 16.8 microg/ml) combined (P < 0.05). Two- and 4-h concentrations of ethambutol in plasma were not affected by AIDS status or gender. The high AC/plasma and AC/ELF concentration ratios suggest that substantial antimycobacterial activity resides in these cells. The data confirm earlier observations of active transport ex vivo of ethambutol into pulmonary macrophages.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Bronchopulmonary disposition of the ketolide telithromycin (HMR 3647).

Telithromycin (HMR 3647) is the first member of a new family of antimicrobials, the ketolides, developed specifically for the treatment of community-acquired respiratory tract infections. Telithromycin has proven in vitro activity against both common and atypical respiratory tract pathogens. The penetration of telithromycin into bronchopulmonary tissues and subsequent elimination from these sites were evaluated in four groups (groups A, B, C, and D) of six healthy male subjects who received telithromycin at 800 mg once daily for 5 days. Subjects in groups A, B, C, and D underwent fiberoptic bronchoscopy and bronchoalveolar lavage 2, 8, 24, and 48 h after receipt of the last dose, respectively. The concentration of telithromycin in the alveolar macrophages, epithelial lining fluid (ELF), and plasma was determined by the agar diffusion method with Bacillus subtilis ATCC 6633 as the test organism. The concentration of telithromycin in alveolar macrophages markedly exceeded that in plasma, reaching up to 146 times the concentration in plasma 8 h after dosing (median concentration, 81 mg/liter). Telithromycin was retained in alveolar macrophages 24 h after dosing (median concentration, 23 mg/liter), and it was still quantifiable 48 h after dosing (median concentration, 2.15 mg/liter). Telithromycin median concentrations in ELF also markedly exceeded concentrations in plasma (median concentration in ELF, 3.7 mg/liter 8 h after dosing). Telithromycin achieves high and sustained concentrations in ELF and in alveolar macrophages, while it maintains adequate levels in plasma, providing an ideal pharmacokinetic profile for effective treatment of community-acquired respiratory tract infections caused by either common or atypical, including intracellular, respiratory tract pathogens.

Administration, Oral↗
PubMed2003

Steady-state plasma and bronchopulmonary concentrations of intravenous levofloxacin and azithromycin in healthy adults.

The purpose of this study was to compare the concentrations of levofloxacin and azithromycin in steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) after intravenous administration. Thirty-six healthy, nonsmoking adult subjects were randomized to either intravenous levofloxacin (500 or 750 mg) or azithromycin (500 mg) once daily for five doses. Venipuncture and bronchoscopy with bronchoalveolar lavage were performed in each subject at either 4, 12, or 24 h after the start of the last antibiotic infusion. The mean concentrations of levofloxacin and azithromycin in plasma were similar to those previously published. The dosing regimens of levofloxacin achieved significantly (P < 0.05) higher concentrations in steady-state plasma than azithromycin during the 24 h after drug administration. The respective mean (+/- standard deviation) concentrations at 4, 12, and 24 h in ELF for 500 mg of levofloxacin were 11.01 +/- 4.52, 2.50 +/- 0.97, and 1.24 +/- 0.55 micro g/ml; those for 750 mg of levofloxacin were 12.94 +/- 1.21, 6.04 +/- 0.39, and 1.73 +/- 0.78 micro g/ml; and those for azithromycin were 1.70 +/- 0.74, 1.27 +/- 0.47, and 2.86 +/- 1.75 micro g/ml. The differences in concentrations in ELF among the two levofloxacin groups and azithromycin were significantly (P < 0.05) higher at the 4- and 12-h sampling times. The respective concentrations in AM for 500 mg of levofloxacin were 83.9 +/- 53.2, 18.3 +/- 6.7, and 5.6 +/- 3.2 micro g/ml; those for 750 mg of levofloxacin were 81.7 +/- 37.0, 78.2 +/- 55.4, and 13.3 +/- 6.5 micro g/ml; and those for azithromycin were 650 +/- 259, 669 +/- 311, and 734 +/- 770 micro g/ml. Azithromycin achieved significantly (P < 0.05) higher concentrations in AM than levofloxacin at all sampling times. The concentrations in ELF and AM following intravenous administration of levofloxacin and azithromycin were higher than concentrations in plasma. Further studies are needed to determine the clinical significance of such high intrapulmonary concentrations in patients with respiratory tract infections.

Adult↗
PubMed1999

Interleukin-2 (IL-2) regulates the accessibility of the IL-2-responsive enhancer in the IL-2 receptor alpha gene to transcription factors.

Interleukin-2 (IL-2) responsiveness of T lymphocytes is controlled through transcription of the IL-2 receptor (IL-2R) alpha subunit by antigen and by IL-2 itself. IL-2 induces IL-2Ralpha transcription via an IL-2-responsive enhancer (IL-2rE), whose activity depends on the cooperative binding of IL-2-induced STAT5 to two sites and of constitutively active Elf-1 to a third one. Here we describe the changes in IL-2rE chromatin that occur in normal T lymphocytes upon activation of IL-2Ralpha expression. In cells induced to transiently express IL-2Ralpha with concanavalin A (which mimics antigen), none of the IL-2rE sites is occupied despite the presence of Elf-1 and STAT1, which bind to the IL-2rE in vitro. The two STAT binding sites are occupied rapidly upon IL-2 stimulation, concomitantly with STAT5 activation. Occupation of the Elf-1 binding site is delayed, although Elf-1 concentration and binding activity are not modified by IL-2. Digestion of T-cell chromatin with DNase I and micrococcal nuclease shows that IL-2 induces the appearance of nuclease-hypersensitive sites flanking the IL-2rE. Thus IL-2, in addition to activating STAT5, appears to regulate IL-2Ralpha transcription by making IL-2Ralpha chromatin accessible to transcription factors.

Animals↗
PubMed2005

EMF and health.

Electric and magnetic fields are ubiquitous in the modern society, and concerns have been expressed regarding possible adverse effects of these exposures. This review covers epidemiologic research on health effects of exposures to static, extremely low-frequency (ELF), and radio frequency (RF) fields. Research on ELF fields has been performed for more than two decades, and the methodology and quality of studies have improved over time. Studies have consistently shown increased risk for childhood leukemia associated with ELF magnetic fields, whereas ELF fields most likely are not a risk factor for breast cancer and cardiovascular disease. There are still inadequate data for other outcomes. More recently, focus has shifted toward RF exposures from mobile telephony. There are no persuasive data suggesting a health risk, but this research field is still immature with regard to the quantity and quality of available data. This technology is constantly changing and there is a need for continued research on this issue. Almost no epidemiologic data are available for static fields.

Abortion, Spontaneous↗
PubMed2006

Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants.

Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O(2) dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.

Bronchoalveolar Lavage Fluid↗
PubMed1997

N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats.

Although the antioxidant properties of N-acetylcysteine (NAC) in vitro are widely accepted, the efficacy of NAC in the prevention of O2 toxicity in vivo is poorly documented. The aim of our study was to investigate the presumed protective effect of NAC on hyperoxic lung injury, focusing on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Thirty-four male Wistar rats were divided in three groups (n = 10-14) and were exposed to air or to 60 or 85% O2 for 7 days. One-half of the rats in each group received 200 mg/kg NAC intraperitoneally one time per day from 3 days before exposure until the end of the experiment, and the other one-half received the vehicle. In the 85% O2-exposed animals, NAC led to more respiratory distress and weight loss. NAC did not prevent the rise in bronchoalveolar lavage lactate dehydrogenase and alkaline phosphatase, but it did prevent the rise in calculated ELF volume. NAC decreased GSH levels (1.4-fold) and gamma-GT activity (1.8-fold) in the air-exposed type II cells. In the 60% O2-exposed group, no effects of NAC were seen (except for a decrease in gamma-GT mRNA expression), but, in the 85% O2-exposed group, NAC gave rise to higher GSH (2.6-fold) and higher gamma-GT activity (2.9-fold) in the ELF and lower GSH (6.9-fold) and higher gamma-GT activity (3.6-fold) in the type II cells. Even in culture, GSH levels remained 1.5-fold lower than in the cells from the air-exposed animals and 2-fold lower than in the cells from the 85% O2-exposed animals. There was increased DNA damage (as assessed by thymidine incorporation) and apoptosis after hyperoxia, especially after 60% O2, and this effect was amplified after NAC treatment. Although protective at the endothelial side, NAC treatment led to adverse effects at the epithelial side, despite, or probably because of, restoration of the ELF GSH levels in the presence of high O2 levels. Because NAC is rapidly metabolized to cysteine, it is plausible that the effects of NAC are manifested through the toxic effects of cysteine.

Acetylcysteine↗
PubMed1998

O3-induced formation of bioactive lipids: estimated surface concentrations and lining layer effects.

Recent evidence suggests that inhaled ozone (O3) does not induce toxicity via direct epithelial interactions. Reactions with epithelial lining fluid (ELF) constituents limit cellular contact and generate products, including lipid ozonation products, postulated to initiate pathophysiological cascades. To delineate specific aspects of lipid ozonation product formation and to estimate in situ surface concentrations, we studied the O3 absorption characteristics of ELF constituent mixtures and measured hexanal, heptanal, and nonanal yields as a function of ascorbic acid (AH2) concentration. Exposures of isolated rat lungs, bronchoalveolar lavage fluid (BALF) and egg phosphatidylcholine (PC) liposomes were conducted. 1) O3 absorption by AH2, uric acid, and albumin exceeded that by egg PC and glutathione. O3 reaction with egg PC occurred when AH2 concentrations were reduced. 2) Aldehydes were produced in low yield during lung and BALF exposures in a time- and O3 concentration-dependent manner. 3) Diminishing BALF AH2 content lowered O3 uptake but increased aldehyde yields. Conversely, AH2 addition to egg PC increased O3 uptake but reduced aldehyde yields. Estimations of bioactive ozonation and autoxidation product accumulation within the ELF suggested possible nanomolar to low micromolar concentrations. The use of reaction products as metrics of O3 exposure may have intrinsic sensitivity and specificity limitations. Moreover, due to the heterogenous nature of O3 reactions within the ELF, dose-response relationships may not be linear with respect to O3 absorption.

Absorption↗
PubMed1991

Interfacial transfer kinetics of NO2 into pulmonary epithelial lining fluid.

Previous studies, both in intact lungs and epithelial lining fluid (ELF) (J. Appl. Physiol. 68: 594-603, 1990 and J. Appl: Physiol. 69: 523-531, 1990), have suggested that the steady-state absorption of inhaled NO2 is mediated by chemical reaction(s) between NO2 and ELF solute reactants. To characterize the kinetics of NO2 absorption into aqueous biological substrates across a gas-liquid interface, we utilized a closed system of known geometry and initial gas phase [NO2] [([NO2]g)0] to expose ELF (as bronchoalveolar lavage; BAL) and a biochemical model system (glutathione, GSH). Assessments of NO2 reactive uptake, into both GSH and ELF, indicated first-order NO2 kinetics [([NO2]g)0 less than or equal to 10.5 ppm] with effective rate constants of (kNO2)GSH = 4.8 and (kNO2)BAL = 2.9 ml.min-1.cm-2 (stirred). Above 10.5 ppm (1 mM GSH), zero-order kinetics were observed. Both (kNO2)GSH and (kNO2)BAL showed aqueous reactant dependence. The reaction order with respect to GSH and BAL was 0.47 and 0.64, respectively. We found no effect of interfacial surface area or bulk phase volume on kNO2. In unstirred systems, significant interfacial resistance was observed and was related to reactant concentration. These results indicate that NO2 reactive uptake follows first-order kinetics with respect to NO2 ([NO2]g less than or equal to 10.5 ppm) and displays aqueous substrate dependence. Furthermore the site of reactive absorption appears to be limited to near the aqueous surface interface. Unstirred conditions confine interfacial mass transfer kinetics in a dose-dependent manner. These phenomenological coefficients may provide the basis for direct extrapolation to environmentally relevant exposure concentrations.

Absorption↗