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PubMed2000

Concentrations of single-dose meropenem (1 g iv) in bronchoalveolar lavage and epithelial lining fluid.

The concentrations of meropenem were measured in plasma, bronchoalveolar lavage (BAL) and epithelial lining fluid (ELF) 0.5-8 h after the administration of a single 1 g iv dose of meropenem. Thirty-five patients undergoing bronchoscopy were studied. Mean concentrations in plasma, BAL and ELF, respectively, measured by high performance liquid chromatography, were as follows: 0.5 h: 25. 96, 0.14, 5.04 mg/L; 1 h: 14.98, 0.09, 7.07 mg/L; 2 h: 12.01, 0.06, 3.86 mg/L; 4 h: 2.51, 0.04, 2.20 mg/L; 6 h: 0.57, 0, 0.59 mg/L; 8 h: 0.29, 0, 0 mg/L. Throughout the 2 h following infusion, concentrations in ELF exceeded the MIC90 for all nosocomial and community-acquired respiratory pathogens, including Pseudomonas aeruginosa (3.05 mg/L), Haemophilus influenzae (0.16 mg/L) and penicillin-resistant Streptococcus pneumoniae (0.86 mg/L). These results support the clinical efficacy of meropenem in the treatment of a wide range of pulmonary infections.

Adult↗
PubMed2001

Lung concentrations of telithromycin after oral dosing.

Concentrations of telithromycin were measured in plasma, bronchial mucosa (BM), epithelial lining fluid (ELF) and alveolar macrophages (AM) following multiple oral doses. Concentrations were determined using a microbiological assay. There were 20 subjects in the study, allocated to three nominal time periods: 2, 12 and 24 h. Mean concentrations in plasma, BM, ELF and AM for 2, 12 and 24 h were as follows: 2 h, 1.86 mg/L, 3.88 mg/kg, 14.89 mg/L and 69.32 mg/L; 12 h, 0.23 mg/L, 1.41 mg/kg, 3.27 mg/L and 318.1 mg/L; and 24 h, 0.08 mg/L, 0.78 mg/kg, 0.97 mg/L and 161.57 mg/L. These concentrations of telithromycin in BM and ELF exceeded for 24 h the mean MIC90s of the common respiratory pathogens Streptococcus pneumoniae (0.12 mg/L) and Moraxella catarrhalis (0.03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Administration, Oral↗
PubMed2002

Rifampicin concentrations in bronchial mucosa, epithelial lining fluid, alveolar macrophages and serum following a single 600 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of rifampicin in epithelial lining fluid (ELF), human alveolar macrophages (AM), bronchial mucosal biopsies and serum were measured after a single oral dose of 600 mg rifampicin from 15 patients undergoing fibre-optic bronchoscopy. The samples of ELF, AM, the bronchial mucosal biopsies and serum were obtained approximately 2-5 h after dosing. The mean concentrations (mean +/- standard error) were 5.25 mg/L (+/-0.67) in ELF, 7.93 mg/kg (+/-1.61) in bronchial biopsies, 15.48 mg/L (+/-1.41) in serum and 251.8 mg/L (+/-65.92) in alveolar macrophages. These site concentrations exceeded the MIC90 for common respiratory pathogens including Mycobacterium tuberculosis and support the observed clinical efficacy of rifampicin in the treatment of a wide range of respiratory tract infections.

Administration, Oral↗
PubMed1992

Electromagnetic field effects on cells of the immune system: the role of calcium signaling.

During the past decade considerable evidence has accumulated demonstrating that nonthermal exposures of cells of the immune system to extremely low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes that might be relevant to in vivo immune activity. A similar responsiveness to nonionizing electromagnetic energy in this frequency range has also been documented for tissues of the neuroendocrine and musculoskeletal system. However, knowledge about the underlying biological mechanisms by which such fields can induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca(2+)-regulated activity is involved in bioactive ELF field coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells and then closely examines new results that suggest a role for Ca2+ in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca2+ signaling processes are involved in the mediation of field effects on the immune system.

Animals↗
PubMed2005

Electromagnetic fields affect transcript levels of apoptosis-related genes in embryonic stem cell-derived neural progenitor cells.

Mouse embryonic stem (ES) cells were used as an experimental model to study the effects of electromagnetic fields (EMF). ES-derived nestin-positive neural progenitor cells were exposed to extremely low frequency EMF simulating power line magnetic fields at 50 Hz (ELF-EMF) and to radiofrequency EMF simulating the Global System for Mobile Communication (GSM) signals at 1.71 GHz (RF-EMF). Following EMF exposure, cells were analyzed for transcript levels of cell cycle regulatory, apoptosis-related, and neural-specific genes and proteins; changes in proliferation; apoptosis; and cytogenetic effects. Quantitative RT-PCR analysis revealed that ELF-EMF exposure to ES-derived neural cells significantly affected transcript levels of the apoptosis-related bcl-2, bax, and cell cycle regulatory "growth arrest DNA damage inducible" GADD45 genes, whereas mRNA levels of neural-specific genes were not affected. RF-EMF exposure of neural progenitor cells resulted in down-regulation of neural-specific Nurr1 and in up-regulation of bax and GADD45 mRNA levels. Short-term RF-EMF exposure for 6 h, but not for 48 h, resulted in a low and transient increase of DNA double-strand breaks. No effects of ELF- and RF-EMF on mitochondrial function, nuclear apoptosis, cell proliferation, and chromosomal alterations were observed. We may conclude that EMF exposure of ES-derived neural progenitor cells transiently affects the transcript level of genes related to apoptosis and cell cycle control. However, these responses are not associated with detectable changes of cell physiology, suggesting compensatory mechanisms at the translational and posttranslational level.

Apoptosis↗
PubMed1999

Light-dependent effects of magnetic fields on nitric oxide activation in the land snail.

The attenuation of opioid analgaesia is a well established effect of extremely low frequency (ELF) magnetic fields with light having a modulatory role in these effects such that when the ELF exposures are carried out in the dark, the inhibitory effects on analgesia are reduced. Here, we considered the light dependency of the effects of exposure to an ELF magnetic field prior to the induction of opioid analgesia. Brief exposure to a 60 Hz field potentiated in a light dependent manner the inhibitory effects of the nitric oxide (NO) precursor L-arginine on the level of subsequent opioid-induced analgesia in the land snail Cepaea nemoralis. This suggests a general light dependency of the actions of magnetic fields and the involvement of NO in the mediation of the effects of magnetic fields.

Analgesics↗
PubMed2000

Elevated levels of interleukin-8 and transforming growth factor-beta in bronchoalveolar lavage fluid from patients with bronchiolitis obliterans syndrome: proinflammatory role of bronchial epithelial cells. Munich Lung Transplant Group.

BACKGROUND: Obliterative bronchiolitis (OB), the most important long-term complication after lung transplantation, is thought to be a manifestation of chronic rejection within the airways, with the hallmarks inflammation and fibroproliferation. METHODS: To characterize the inflammatory process in the context of OB we quantified tumor necrosis factor-alpha, interleukin (IL)-8, IL-10, and transforming growth factor (TGF)-beta on the protein and mRNA level in bronchoalveolar lavage fluid samples obtained from patients with bronchiolitis obliterans syndrome (BOS) and without BOS. In addition, bronchial cells sampled by bronchial brushing were analyzed for mRNA expression. RESULTS: In respiratory epithelial lining fluid (ELF) from BOS patients the protein levels of IL-8 (52.4+/-22.2 vs. 4.4+/-0.9 pg/ml ELF, P<0.005) and TGF-beta (5.6+/-1.9 vs. 0.9+/-0.2 ng/ml ELF, P<0.005) were significantly elevated. In addition, bronchoalveolar lavage fluid cells of BOS patients showed increased expression of TGF-beta (1.13+/-0.44 vs. 0.45+/-0.16, optical density [O.D.]/O.D. glyceraldehyde-3-phosphate dehydrogenase [GAPDH], P=0.11) and IL-8 (0.25+/-0.13 vs. 0.09+/-0.03 O.D/O.D. GAPDH, P=0.53) without the differences reaching statistical significance. In contrast, IL-8 mRNA expression of bronchial cells was significantly higher in the BOS group (0.85+/-0.40 vs. 0.22+/-0.10 O.D./O.D. GAPDH, P<0.05). CONCLUSIONS: We assume that IL-8 and TGF-beta may act as key mediators for airway inflammation and fibroproliferation in the pathogenesis of OB, with bronchial epithelial cells serving as a relevant source of IL-8.

Adult↗
PubMed1996

Extra low frequency electric and magnetic fields in the bedplace of children diagnosed with leukaemia: a case-control study.

This retrospective case-control study of 56 cases and 56 controls measured extra low frequency (ELF) electric and magnetic fields between 2000 h and 0800 h in the bedplaces of children with leukaemia. Mean ELF electric field (E-field) levels found in case homes of 13.9 Vm-1 (SD: 13.6) were significantly higher (P < 0.01) compared with only 7.3 Vm-1 (SD: 12.9) in controls matched for age and sex. Moreover, applying conditional logistic regression, a dose-response relationship emerged between E-field exposure and incidence: above 20 Vm-1 the relative risk was 4.69 (95% CI: 1.17-27.78; P = 0.025), whereas at levels of 10-19 Vm-1 it was 2.40 (95% CI: 0.79-8.09) and at levels of 5-9 Vm-1 it was only 1.46 (95% CI: 0.47-5.10). By contrast, similar readings of the rms ELF magnetic field found no significant case-control differences: mean levels in cases' homes of 0.070 microT (SD: 0.070) compared with 0.057 microT (SD: 0.038) in controls. Although there were imperfections in the study design, it is concluded that the importance of the E-field may have been overlooked in epidemiological studies to date.

Adolescent↗
PubMed2002

Effects of chronic hepatic dysfunction on pulmonary glutathione homeostasis.

BACKGROUND: The development of acute respiratory distress syndrome (ARDS) in patients with pre-existing cirrhosis of the liver is associated with very high mortality. One possible cause may be alteration of pulmonary antioxidant capacity as a result of chronic hepatic dysfunction. Glutathione (GSH) is the most substantial nonprotein thiol in living organisms and likely plays a key role in neutralizing the oxidants and reactive oxygen species that are increased in ARDS. The lung is unable to synthesize GSH and is dependent on the liver. During periods of oxidant stress, individuals may exhibit relative deficiencies of GSH. With cirrhosis, the end result of chronic alcohol ingestion, this deficiency is more profound. METHODS: Sixteen stable subjects with cirrhosis primarily due to alcohol consumption and 15 healthy controls underwent bronchoscopy and bronchoalveolar lavage with concurrent measurement of GSH in the plasma and the alveolar epithelial lining fluid (ELF). RESULTS: For standardizing for saline dilution of the epithelial lining fluid as a result of bronchoalveolar lavage, GSH values are expressed in relation to immunoglobulin A (IgA). GSH in the ELF was profoundly reduced in the cirrhotic group [12.5 microg of GSH per microg of IgA (5.3-16.9 microg)] compared with the control group [64.0 microg of GSH per microg of IgA (55.1-242.5 microg); < 0.001]. The ratio of oxidized GSH to total GSH in the ELF was also significantly increased in the cirrhotic group [9.2% (5.1-16.4%) vs. 3.4% (1.7-5.7%); p < 0.003]. CONCLUSIONS: Despite a total reduction in GSH concentrations in the alveolar epithelial lining fluid of individuals with cirrhosis, the amount of oxidized GSH is increased. There is increased utilization of GSH despite the low supply in stable individuals with cirrhosis during steady state. These perturbations in GSH homeostasis in the alveolar epithelial lining fluid may be a factor in the poor outcomes seen in these individuals with ARDS.

Adult↗
PubMed2003

Maternal occupational exposure to extremely low frequency magnetic fields during pregnancy and childhood leukemia.

BACKGROUND: Pregnancy is a target period for events that could induce childhood leukemia. There has been little attention to possible effects of maternal occupational exposure to extremely low frequency magnetic fields (ELF-MF) during pregnancy. METHODS: We conducted a population-based, case-control study of 491 incident cases of acute lymphoblastic leukemia in children 0-9 years of age, matched on age and sex to 491 healthy controls. Cases were diagnosed in the Province of Québec between 1980 and 1993. Mothers were interviewed to obtain detailed prenatal occupational history; individual exposure to ELF-MF was estimated based on a method we recently developed. We used 3 metrics for analyzing exposure: cumulative, average and maximum levels. Analyses were carried out among all study women and among working women only. RESULTS: Comparing the highest 10% of exposed mothers to the others, the risk of leukemia among offspring was moderately increased by using any metric, in all women and among working women only. The highest odds ratio of 2.5 (95% confidence interval = 1.2-5.0) was found for maximum exposure attained in an occupation (>/=0.4 microtesla). CONCLUSIONS: Our results are compatible with an increased risk of childhood leukemia among children whose mothers were exposed to the highest occupational levels of ELF-MF during pregnancy.

Adult↗
PubMed2004

Association of cytomegalovirus DNA concentration in epithelial lining fluid and symptomatic cytomegalovirus infection in lung transplant recipients.

BACKGROUND: The authors have investigated the effectiveness of virus detection from bronchoalveolar lavage (BAL) samples for the identification of symptomatic cytomegalovirus (CMV) infection in lung transplant recipients. METHODS: Thus, 275 BAL samples taken from 105 lung transplant recipients during follow-up were analyzed by quantitative polymerase chain reaction (PCR) and virus isolation. RESULTS: Quantitative PCR detected virus in all 24 BAL samples taken at onset of symptomatic disease, and virus culture in only 7 samples (29.2%). Twenty-three of 251 BAL samples (9.2%) were positive by PCR, although they were obtained in an asymptomatic phase. Quantitation of CMV DNA from BAL allowed no discrimination between symptomatic and asymptomatic infection in individual cases. However, when the urea dilution method was used to recalculate the CMV DNA concentration for the epithelial lining fluid (ELF) diluted in the BAL, a CMV DNA level of more than 10 copies/mL ELF was clearly associated with symptomatic disease. CONCLUSION: The CMV DNA level in ELF may be a marker for symptomatic CMV infection.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Electron localization functions obtained from X-ray constrained Hartree-Fock wavefunctions for molecular crystals of ammonia, urea and alloxan.

Constrained Hartree-Fock wavefunctions in the superposition of isolated molecules model have been calculated from precise X-ray diffraction data on crystals of ammonia (NH(3)), urea [CO(NH(2))(2)] and alloxan [(CO)(4)(NH)(2)]. The X-ray constrained wavefunctions have been used to derive and examine 'electron localization' information, quantified by the true and approximate electron localization function (ELF), and the true and approximate Fermi hole mobility function (FHMF). The plots of the Fermi hole mobility function are the first to appear in the literature. The results are compared with corresponding isolated-molecule Hartree-Fock calculations to gauge the effect of the crystal environment on the isolated molecules. An error analysis is performed to indicate the features in the plots which are well determined from the experimental data. The results from all plots are broadly consistent, but the approximate ELF shows some artifacts relative to the true ELF.

Journal Article↗
PubMed1995

Soluble ICAM-1 as a regulator of nasal allergic reaction under natural allergen provocation.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) plays a key role in the early stage of the signal cascade leading to cellular extravasation and development of an inflammatory response. Recently, it has been reported that the soluble form of this adhesion molecule is present in human sera, possibly mediating biological actions. OBJECTIVE: The purpose of this study was to investigate levels of soluble ICAM-1 (sICAM-1) and its receptors in patients with allergic rhinitis, and to discuss sICAM-1's biological function. METHODS: The levels of sICAM-1 in sera and nasal epithelial lining fluids (ELF), the percentage of CD11a-positive lymphocytes in the peripheral blood, and scores of subjective symptoms from 14 patients with pollinosis (allergic group) were measured from pre- to post-season, results were compared with those from 10 non-allergic subjects (control group). RESULTS: The levels of sICAM-1 in sera and ELF were upregulated, and CD11a-positive lymphocytes were downregulated during the in-season in the allergic group. In addition, levels of sICAM-1 sera from the allergic group remained high during the post-season, when levels of other parameters (symptoms, blood eosinophil counts, sICAM-1 in ELF and CD11a-positive lymphocytes) had roughly returned to the initial pre-season levels. CONCLUSIONS: We demonstrate systemic and local upregulation of sICAM-1 and systemic downregulation of LFA-1 positive lymphocytes in patients with seasonal allergic rhinitis under natural allergen provocation, suggesting that sICAM-1 plays a role in regulating seasonal allergic inflammation.

Adult↗
PubMed1997

Fluconazole in cats: pharmacokinetics following intravenous and oral administration and penetration into cerebrospinal fluid, aqueous humour and pulmonary epithelial lining fluid.

The pharmacokinetics of fluconazole following intravenous (i.v.) and oral (p.o.) administration and the penetration of fluconazole into cerebrospinal fluid, aqueous humour and epithelial lining fluid (ELF) of the lungs were evaluated in adult male cats. Pharmacokinetic parameters were calculated from serum concentration-time data obtained following i.v. and p.o. administration of 50 mg per cat using a cross-over study design. Fluconazole concentrations were measured using a high-performance liquid chromatography assay. Mean total body clearance of fluconazole was 37.7 mL/h.kg, mean volume of distribution at steady state was 1.14 L/kg, mean residence time was 31.0 h and mean half-life of elimination was 25 h as derived by non-compartmental analysis of data. Absorption was complete. Mean ratios of fluid:serum fluconazole concentrations following administration of 50 mg fluconazole per day for 8 days were as follows: cerebrospinal fluid, 0.88; aqueous humour 0.79; ELF, 1.20. Fluconazole concentrations in cerebrospinal fluid, aqueous humour and ELF exceeded reported minimum inhibitory concentrations of fluconazole for pathogenic fungi. Results of this study suggest fluconazole can effectively be administered to cats at 50 mg per cat per day.

Administration, Oral↗
PubMed1999

Functional and compositional changes in pulmonary surfactant in response to exercise.

Pulmonary surfactant from bronchoalveolar lavages was obtained from 2 groups of horses. A control group consisting of 6 healthy racehorses that were paddock-rested and lavaged weekly for 6 consecutive weeks were compared with an experimental group of 10 healthy racehorses, lavaged weekly the same period, consisting of a 5 week incremental-intensity treadmill training programme and one week post training paddock rest. Phospholipid content of lavage fluid was determined indirectly by phosphorus assay, and surfactant functional activity was determined by bubble surfactometry. Total cell counts and differential cell percentages of lavage fluid were adjusted to reflect the dilution of alveolar epithelial lining fluid (ELF) using the lavage/serum urea ratio, and data were analysed per volume of ELF. There was no change in phospholipid content for either group, but some horses had consistently greater amounts than did others, ranging from 17.2-64.4 micrograms/microliter. From the exercised group ELF had both increased nucleated cell numbers due to increased macrophage numbers, and increased numbers of erythrocytes. Surface tension increased significantly over the exercise protocol, but not in controls. Functional activity of surfactant varied between horses, independent of phospholipid content, with average values for individuals ranging 10.5-29.5 mN/m. We conclude that exercise of sufficient intensity to induce intrapulmonary haemorrhage also leads to functional decrease in surfactant activity, without affecting phospholipid content. This study also indicates that functional differences in surfactant exist between horses and may be a risk factor for development of exercise-induced pulmonary haemorrhage.

Animals↗
PubMed1992

Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients.

The pulmonary disposition of cefpodoxime was studied in 12 patients with pulmonary opacities after a single oral dose of 260 mg of cefpodoxime-proxetil, which is equivalent to 200 mg of cefpodoxime. Blood and lung tissue samples were collected during surgery, and bronchoalveolar lavage was carried out 3 h (group A) or 6 h (group B) after drug administration. Urea was used as an endogenous marker for measurement of the volume of epithelial lining fluid (ELF). Concentrations were measured by using a microbiological assay. The mean concentrations of cefpodoxime in plasma, ELF, and lung tissue were, respectively, 1.85 +/- 0.82 mg/liter, 0.22 +/- 0.13 mg/liter, and 0.89 +/- 0.80 mg/kg of body weight in group A and 1.40 +/- 1.25 mg/liter, 0.12 +/- 0.14 mg/liter, and 0.84 +/- 0.61 mg/kg in group B. Concentrations in lung parenchyma 6 h after dosing were at least equal to or above the MICs for 90% of the strains of most organisms commonly found in respiratory tract infections, whereas data for ELF suggest levels of drug insufficient to inhibit bacteria.

Administration, Oral↗
PubMed1996

Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin.

The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers. Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose. The concentrations (mean +/- standard deviation) of CLA, 14-hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high-performance liquid chromatography assay. The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects. The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively). However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma. These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.

Adult↗
PubMed1996

Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses.

The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high-performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean +/- standard deviation, 464 +/- 65 micrograms/ml) exceeded 80 micrograms/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 +/- 28 micrograms/ml) exceeded 20 micrograms/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 +/- 0.93 micrograms/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is nuclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

Adult↗