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 469 records · Page 26Linked to original sources
PubMed2001

In vitro activity and pharmacodynamics of azithromycin and clarithromycin against Streptococcus pneumoniae based on serum and intrapulmonary pharmacokinetics.

BACKGROUND: Multidrug-resistant strains of Streptococcus pneumoniae are increasingly common worldwide, but the clinical significance of their resistance to the macrolide antibiotics is controversial. Applying pharmacokinetic and pharmacodynamic principles can assist in the selection of appropriate antimicrobial therapy. OBJECTIVES: The purpose of this study was to determine the in vitro activity of penicillin, azithromycin, clarithromycin, and clindamycin against clinical isolates of S. pneumoniae and to evaluate the pharmacodynamics of azithromycin and clarithromycin based on serum and epithelial lining fluid (ELF) concentrations. METHODS: The minimum inhibitory concentrations (MICs) of penicillin, azithromycin, clarithromycin, and clindamycin were determined for 307 isolates of S. pneumoniae using broth microdilution. Using serum and ELF concentrations after standard dosing, we calculated the proportion of isolates against which it would be possible to obtain a ratio of azithromycin area under the curve to MIC > or =25 and clarithromycin concentrations that exceeded the MIC for > or =40% of the dosing interval. RESULTS: Overall, 19.5%, 25.4%, 25.1%, and 7.2% of the 307 pneumococcal isolates were resistant to penicillin, azithromycin, clarithromycin, and clindamycin, respectively. However, 71.7% of penicillin-resistant strains were also resistant to azithromycin and clarithromycin. Based on serum concentrations, clarithromycin achieved its pharmacodynamic target in 76.9% of isolates, compared with 59.9% for azithromycin. Based on ELF concentrations, clarithromycin achieved its pharmacodynamic target in 93.5% of isolates, compared with 74.6% for azithromycin. Based on ELF concentrations, clarithromycin achieved its pharmacodynamic target in 86.7% of penicillin-resistant isolates, compared with 28.3% for azithromycin. CONCLUSIONS: On the basis of serum and ELF concentrations, clarithromycin achieved pharmacodynamic targets against a greater proportion of S. pneumoniae isolates than did azithromycin. Clinical studies are needed to determine the efficacy of these agents against pneumococci that demonstrate in vitro resistance using current susceptibility breakpoints.

Anti-Bacterial Agents↗
PubMed1998

Brief exposure of mice to 60 Hz magnetic fields reduces the analgesic effects of the neuroactive steroid, 3alpha-hydroxy-4-pregnen-20-one.

Relatively weak, extremely low frequency (ELF), magnetic fields have been shown to exert a variety of biological effects, although the modes of action remain to be established. Neuroactive steroids and neurosteroids have been shown to produce a diverse range of rapid centrally mediated behavioral and physiological effects that are reported to be sensitive to magnetic fields. Here we show that brief exposure of male mice to an ELF magnetic field (30 min, 60 Hz, 141 microT peak) significantly reduces the analgesic effects arising from intracerebroventricular (i.c.v.) administration of the centrally produced allylic neuroactive steroid, 3alpha-hydroxy-4-pregnen-20-one (3alphaHP) and that the dihydropyridine (DHP) calcium channel antagonists, diltiazem and nifedipine, block the inhibitory effects of the 60 Hz ELF on 3alphaHP-induced analgesia. These results indicate that exposure to 60 Hz ELF affects the analgesic effects of neuroactive steroids such as 3alphaHP through alterations in calcium channel function. These findings raise the possibility that ELF magnetic fields may, in part, exert their actions through effects on diverse neuroactive steroid modulated processes.

20-alpha-Dihydroprogesterone↗
PubMed2002

Induction of DNA strand breaks by intermittent exposure to extremely-low-frequency electromagnetic fields in human diploid fibroblasts.

Results of epidemiological research show low association of electromagnetic field (EMF) with increased risk of cancerous diseases and missing dose-effect relations. An important component in assessing potential cancer risk is knowledge concerning any genotoxic effects of extremely-low-frequency-EMF (ELF-EMF). Human diploid fibroblasts were exposed to continuous or intermittent ELF-EMF (50Hz, sinusoidal, 24h, 1000microT). For evaluation of genotoxic effects in form of DNA single- (SSB) and double-strand breaks (DSB), the alkaline and the neutral comet assay were used. In contrast to continuous ELF-EMF exposure, the application of intermittent fields reproducibly resulted in a significant increase of DNA strand break levels, mainly DSBs, as compared to non-exposed controls. The conditions of intermittence showed an impact on the induction of DNA strand breaks, producing the highest levels at 5min field-on/10min field-off. We also found individual differences in response to ELF-EMF as well as an evident exposure-response relationship between magnetic flux density and DNA migration in the comet assay. Our data strongly indicate a genotoxic potential of intermittent EMF. This points to the need of further studies in vivo and consideration about environmental threshold values for ELF exposure.

Adult↗
PubMed1998

The genotoxic potential of electric and magnetic fields: an update.

We review 23 studies on the potential genotoxicity of electric and magnetic fields that have appeared in the published literature since our 1993 review of 55 published studies (McCann et al., Mutat. Res. 297 (1993) 61-95) and six additional studies published prior to 1993, which were not previously reviewed. As in our previous review, internal electric fields present in media (for in vitro experiments) and in the torso (for in vivo experiments) were estimated. Individual experiments are evaluated using basic data quality criteria. The potential for genotoxicity of electric and magnetic fields is discussed in light of the significant body of genotoxicity data that now exists. Three unsuccessful attempts to replicate previously reported positive results have appeared since our previous review. We conclude that, in spite of the 34 studies reviewed in this and our previous publication that report positive genotoxic effects, none satisfy all of three basic conditions: independent reproducibility, consistency with the scientific knowledge base, and completeness according to basic data quality criteria. As we discuss, these criteria are satisfied for several groups of negative studies in several exposure categories (ELF magnetic fields, 150 microT-5 mT, combined ELF electric and ELF magnetic fields, approx. 0.2 mT, 240 mV/m, and static magnetic fields, 1-3.7 T). The evidence reviewed here strengthens the conclusion of our previous review, that the preponderance of evidence suggests that ELF electric or magnetic fields do not have genotoxic potential. Nevertheless, a pool of positive results remains, which have not yet been tested by independent replication. Among the 12 studies reviewed here, which report statistically significant or suggestive positive results, we point particularly to results from five laboratories [J. Miyakoshi, N. Yamagishi, S. Ohtsu, K. Mohri, H. Takebe, Increase in hypoxanthine-guanine phosphoribosyl transferase gene mutations by exposure to high-density 50-Hz magnetic fields, Mutat. Res. 349 (1996) 109-114; J. Miyakoshi, K. Kitagawa, H. Takebe, Mutation induction by high-density, 50-Hz magnetic fields in human MeWo cells exposed in the DNA synthesis phase, Int. J. Radiat. Biol. 71 (1997) 75-79; H. Lai. N.P. Singh, Acute exposure to a 60-Hz magnetic field increases DNA strand breaks in rat brain cells, Bioelectromagnetics, 18 (1997) 156-165; H. Lai, N.P. Singh, Melatonin and N-tert-butyl-alpha-phenylnitrone block 60-Hz magnetic field-induced DNA single and double strand breaks in rat brain cells, J. Pineal Res. 22 (1997) 152-162; T. Koana, M. Ikehata, M. Nakagawa, Estimation of genetic effects of a static magnetic field by a somatic cell test using mutagen-sensitive mutants of Drosophila melanogaster, Bioelectrochem. Bioenergetics 36 (1995) 95-100; F.L. Tabrah, H.F. Mower, S. Batkin, P.B. Greenwood, Enhanced mutagenic effect of a 60-Hz time-varying magnetic field on numbers of azide-induced TA100 revertant colonies, Bioelectromagnetics 15 (1994) 85-93; S. Tofani, A. Ferrara, L. Anglesio, G. Gilli, Evidence for genotoxic effects of resonant ELF magnetic fields, Bioelectrochem. Bioenergetics, 36 (1995) 9-13], which satisfy most basic data quality criteria and may be of interest.

Animals↗
PubMed1999

Elevated soluble tumor necrosis factor receptor levels in seasonal allergic rhinitis patients.

In this study, we examined the symptom scores and tumor necrosis factor-alpha (TNF-alpha), p55 soluble tumor necrosis factor receptor (sTNFR1), and p75 soluble tumor necrosis factor receptor (sTNFR2) levels in the sera and nasal epithelial lining fluids (ELF) of 20 patients with Japanese cedar pollinosis from the pre- to the postseason period, and compared the results with those of 10 nonallergic control subjects. The symptom scores of the allergic subjects were significantly (P<0.01) higher than those of the nonallergic subjects during the early stage and mid-stage of the season. There were no statistical differences between the allergic and nonallergic subjects in the TNF-alpha levels in sera and ELF from the pre- to the postseason. In the allergic subjects, however, the levels of sTNFR1 and sTNFR2 in ELF were significantly elevated during the early stage (P<0.05) and mid-stage (P<0.01) of the season, whereas those in sera did not change from the pre- to the post-season period. The levels of TNF-alpha in ELF were more than 10 times higher than those in sera, whereas the levels of sTNFR1 and sTNFR2 in ELF were less than half of those in sera in the allergic and nonallergic subjects. These results suggest that sTNFR1 and sTNFR2 may play a role in the pathogenesis of nasal allergic reaction.

Adult↗
PubMed1999

Soluble TNF-alpha receptor and IL-1 receptor antagonist elevation in BAL in active pulmonary TB.

Accumulating evidence suggests that patients with active pulmonary tuberculosis (TB) have an alveolar inflammation resulting in the release of tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta in bronchoalveolar epithelial fluid. It was proposed that the levels of these cytokines would correlate with clinical status parameters (extent of pulmonary involvement, fever, and body weight loss) and that their naturally occurring inhibitors would be concomitantly released in the local inflammatory sites. To test this hypothesis lung epithelial lining fluid (ELF) obtained by bronchoalveolar lavage and serum were collected from 29 patients with active pulmonary TB and 15 healthy subjects to determine the levels of these variables using a sandwich enzyme-linked immunosorbent assay (ELISA). ELF levels of TNF-alpha, soluble (s)TNF receptor I (RI), sTNF-receptor II (RII) and interleukin-1 receptor antagonist (IL-1RA) but not IL-1beta, and their serum levels except for sTNF-RII and IL-1beta were significantly higher in TB patients. Nevertheless, only ELF levels of TNF-alpha and IL-1beta were significantly correlated with disease status. No correlation was found between TNF-alpha levels and those of sTNF-RI and sTNF-RII, nor between IL-1beta and IL-1RA in ELF and serum of TB patients, although there was a significant correlation between sTNF-RI and sTNF-RII levels both in ELF and serum. These findings suggest local release of tumour necrosis factor-alpha and interleukin-1beta and a correlation with disease status. Soluble tumour necrosis factor-alpha receptors and interleukin-1beta receptor antagonist, although increased in lung epithelial lining fluid and serum in tuberculosis patients, were not correlated with tumour necrosis factor-alpha and interleukin-1beta or with disease status.

Adult↗
PubMed2006

Accuracy of short-term residential measurement in the prediction of 72-h exposure to power frequency magnetic field in households very close to high-tension transmission lines.

Between February and April 2003, a total of 80 single-dwelling households close (< 70 m) to high-tension (161 or 345 kV) power lines in a northern community of Taiwan received measurements of indoor extremely low-frequency (ELF) magnetic field for 72 h. Measurements were performed with EMDEX II meter at a sampling rate of every 300 s, yielding some 860 readings of ELF magnetic field for each household. In addition to the 72-h mean ELF magnetic field, we also calculated arithmetic means of the first 2, 6, 12, and 288 readings taken in each household to represent the information on spot, 30-min, 60-min, and 24-h exposures, respectively. The mean 72-h exposure to ELF magnetic field for the 80 study households was estimated at 0.80 micro-Tesla (microT) with a standard deviation (SD) of 1.13 microT. The mean for pot, 30-min, 60-min, and 24-h exposure was 0.88 (SD 1.38), 0.90 (SD 1.40), 0.9 (SD 1.17), and 0.83 (SD 1.17) microT, respectively. There were high agreements, indicated by a nearly perfect intra-class correlation coefficient, between 72-h mean exposure and those short-term exposure measures. Additionally, the sensitivity and specificity of various short-term exposures in the prediction of 72-h exposure greater than 0.4 microT were similar at values of 0.82-0.87 and 0.93-0.95, respectively. This study indicates that short-term measurements of indoor ELF magnetic field seem adequate to represent the mean 72-h exposure, but tended to overpredict 72-h exposure greater than 0.4 microT. Further investigation is needed to assess whether these findings can be replicated in households far away from high-tension power lines.

Electric Power Supplies↗
PubMed2004

Cell activating capacity of 50 Hz magnetic fields to release reactive oxygen intermediates in human umbilical cord blood-derived monocytes and in Mono Mac 6 cells.

The aim of this study was to investigate the mechanism of cell activation induced by extremely low frequency magnetic fields (ELF-MF) (50 Hz) in human cells. We examined the production of free radicals in human umbilical cord blood-derived monocytes and in human Mono Mac 6 cells. The release of superoxide radical anions was analyzed using nitroblue tetrazolium chloride and the total of reactive oxygen species (ROS) was detected using dihydrorhodamine 123. Our results show a significant increase of superoxide radical anion production up-to 1.4 fold as well as an increase in ROS release up-to 1.2 fold upon exposure of monocytes to 1 mT ELF-MF (45 min). Mono Mac 6 cells exhibit higher superoxide radical anion and ROS production up-to 1.4 and 1.5 fold, respectively. These results indicate that Mono Mac 6 cells are more sensitive to ELF-MF than monocytes. Using diphenyleneiodonium chloride (DPI) a specific inhibitor for the NADPH oxidase, the MF-effect was not inhibited in Mono Mac 6 cells. Therefore, we suggest that ELF-MF exposure induces the activation of NADH oxidase in these cells. However, the MF-effect was inhibited by DPI in monocytes, indicating the activation of the NADPH oxidase after exposure to ELF-MF.

Cell Line↗
PubMed2000

Evaluation of the effects of extremely low frequency electromagnetic fields on mammalian follicle development.

The aim of this study was to evaluate the effects of pulsed, extremely low-frequency electromagnetic fields (ELF-EMF) on in-vitro mouse pre-antral follicle development. Pre-antral follicles were cultured for 5 days and exposed to ELF-EMF at the frequencies of 33 or 50 Hz. ELF-EMF application did not affect follicular growth over a 3 day culture period, but on day 5 the growth of 33 Hz-exposed follicles was significantly reduced when compared with controls, while the 50 Hz-exposed follicles were not significantly affected. However, ELF-EMF severely impaired antrum formation at both frequencies, as 79 +/- 3% of control follicles developed antral cavities compared with 30 +/- 6% and 51.6 +/- 4% of 33 or 50 Hz-exposed follicles respectively. The follicles with failed antrum formation showed lower oestradiol release and granulosa cell DNA synthesis, but these effects were not related to granulosa cell apoptosis. Furthermore, a high percentage of the in-vitro grown oocytes obtained from exposed follicles had a reduced ability to resume meiotic maturation when compared with controls. These results suggest that ELF-EMF exposure might impair mammalian female reproductive potentiality by reducing the capacity of the follicles to reach a developmental stage that is an essential pre-requisite for reproductive success.

Animals↗
PubMed1992

Bronchoalveolar distribution of cefuroxime axetil and in-vitro efficacy of observed concentrations against respiratory pathogens.

The concentrations of cefuroxime in human alveolar macrophages (AM), epithelial lining fluid (ELF), bronchial mucosal biopsies and serum were measured after a single dose, equivalent to 500 mg of cefuroxime base, given in the form of the orally-administered pro-drug, cefuroxime axetil. Fourteen patients undergoing fibreoptic bronchoscopy with bronchoalveolar lavage were studied. The mean ELF concentration was 0.7 mg/L, that of bronchial biopsies was 1.8 mg/kg and that of serum 3.5 mg/L. AM-associated cefuroxime was detected in nine patients. To assess the in-vitro activity of the concentrations achieved at the potential sites of infection, clinical isolates of common respiratory pathogens were exposed to two concentrations of cefuroxime, based on the observed concentrations in ELF and bronchial mucosa. ELF and mucosal site concentrations were effective against Streptococcus pneumoniae (except one strain with reduced susceptibility to benzyl penicillin) and Haemophilus influenzae. The ELF concentration was less effective against Moraxella catarrhalis.

Aged↗
PubMed1996

Distribution of cefdinir, a third generation cephalosporin antibiotic, in serum and pulmonary compartments.

The distribution of a new cephalosporin, cefdinir, in serum, epithelial lining fluid (ELF), bronchial mucosa and alveolar macrophages was studied in 17 adults following a single oral dose of 300 or 600 mg of cefdinir; tissue samples being obtained by diagnostic bronchoscopy approximately 4 h after this dose. Mucosal biopsies were taken, alveolar macrophages harvested by lavage, and ELF volume derived from urea concentrations in bronchial lavage fluid and blood. A microbiological assay for cefdinir was performed in serum, bronchial mucosa, ELF and alveolar macrophages. In patients taking 300 mg of cefdinir, the median concentrations of cefdinir were 2.00 mg/L (range 1.40-8.00) in serum, 0.78 mg/L (range 0-1.33) in bronchial mucosa, and 0.29 mg/L (range 0-4.73) in ELF. In patients taking 600 mg, the median concentrations were 4.20 mg/L (range 3.05-6.40) in serum, 1.14 mg/L (range 0-1.92) in bronchial mucosa, and 0.49 mg/L (range 0-0.59) in ELF. Cefdinir did not penetrate macrophages.

Administration, Oral↗
PubMed2006

Azithromycin iv pharmacodynamic parameters predicting Streptococcus pneumoniae killing in epithelial lining fluid versus serum: an in vitro pharmacodynamic simulation.

OBJECTIVES: To investigate the azithromycin pharmacodynamic parameters predicting bacterial killing in epithelial lining fluid (ELF) versus serum against macrolide-susceptible and -resistant Streptococcus pneumoniae isolates (with different resistance genotypes), through the simulation of concentrations achieved after a 500 mg intravenous (iv) once a day regimen. METHODS: An in vitro computer-controlled pharmacodynamic simulation of human azithromycin concentrations in serum and ELF was carried out, and colony counts were determined over 24 h. Four strains with MIC values (mg/L) of 0.5 [mef(A) and erm(B) negative], 2 [mef(A) positive and erm(B) negative], 8 [mef(A) positive and erm(B) negative] and 256 [mef(A) negative and erm(B) positive] were used. RESULTS: Significant (P < 0.05) azithromycin antibacterial activity versus antibiotic-free controls was found in serum and ELF against the susceptible and mef(A) positive strains, but not against the erm(B) positive strain. AUC(0-24)/MIC values around or higher than 25 were needed to achieve (time to 99.9% reduction of initial inocula of around 6 h) and maintain (24 h inocula reduction > or =3 log(10)cfu/mL) bactericidal activity without regrowth. This was achieved only with the susceptible strain in serum, but also with the mef(A) positive strain exhibiting an MIC of 2 mg/L in ELF. CONCLUSIONS: The results of this study support that the suggested breakpoint for susceptibility (< or =2 mg/L) may be adequate to predict S. pneumoniae eradication with ELF but not with serum concentrations obtained after a 500 mg iv once a day regimen.

Anti-Bacterial Agents↗
PubMed1987

Interaction of extremely low frequency electric and magnetic fields with humans.

The dosimetry and physical interaction mechanisms of electromagnetic fields with frequencies in the extremely low frequency (ELF) range (below 300 Hz) are described. The mechanisms through which ELF electric and magnetic fields induce electric currents in living organisms are summarized, with particular emphasis on humans. Topics that are discussed include: (1) sources and measurements of ELF electric and magnetic fields; (2) direct and indirect coupling of these fields to humans; (3) transient discharges and contact currents, and the thresholds for human response to these phenomena; (4) protective measures for the mitigation of potential ELF field effects on humans; and (5) mechanisms of interaction of ELF fields with cellular and tissue systems, with emphasis on field transduction mechanisms involving the cell membrane.

Electricity↗
PubMed2003

Surfactant kinetics in preterm infants on mechanical ventilation who did and did not develop bronchopulmonary dysplasia.

OBJECTIVE: To characterize surfactant kinetics in vivo in two groups of premature infants on different levels of mechanical ventilation and at different risk of developing bronchopulmonary dysplasia. DESIGN: Controlled observational study in two independent groups of infants. SETTING: Neonatal intensive care unit. PATIENTS: Thirteen preterm infants (26 +/- 0.5 wks, birth weight 801 +/- 64 g) on high ventilatory setting and who finally all developed bronchopulmonary dysplasia (MechVentBPD), and eight (26 +/- 0.5 wks, birth weight 887 +/- 103 g) who had minimal or no lung disease and of whom none developed bronchopulmonary dysplasia (MechVentNoBPD). MEASUREMENTS AND MAIN RESULTS: Endotracheal 13C-labeled dipalmitoyl-phosphatidylcholine was administered and subsequent measurements of the 13C enrichment of surfactant-disaturated phosphatidylcholine (DSPC) from serial tracheal aspirates were made by gas chromatography-mass spectrometry. We calculated disaturated phosphatidylcholine pharmacokinetic variables in terms of half-life and apparent pool size from the enrichment decay curves over time. DSPC concentration from tracheal aspirates was expressed as milligrams/milliliter epithelial lining fluid (ELF-DSPC). Data are presented as mean +/- se. In MechVentBPD infants vs. MechVentNoBPD, ELF-DSPC was much reduced, 2.9 +/- 0.6 vs. 9.4 +/- 3.0 mg/mL ELF (p =.03), half-life was shorter, 19.4 +/- 2.8 vs. 42.5 +/- 6.3 hrs (p =.002), and apparent pool size larger, 136 +/- 21 vs. 65.8 +/- 16.0 mg/kg (p =.057). In MechVentBPD, apparent DSPC pool size positively correlated with mean airway pressure x Fio(2) and inversely correlated with ELF-DSPC. ELF-DSPC was inversely correlated with mean airway pressure x Fio(2). No significant correlations were found in the MechVentNoBPD group. CONCLUSIONS: MechVentBPD infants showed profound alteration of surfactant kinetics compared with preterm infants with minimal lung disease, and these alterations were correlated with severity of ventilatory support.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2003

Neurodegenerative diseases in welders and other workers exposed to high levels of magnetic fields.

BACKGROUND: Previous work has suggested an increase in risk of amyotrophic lateral sclerosis (ALS) and Alzheimer's disease among workers exposed to extremely low-frequency magnetic fields (ELF-MF). We evaluated the relation between ELF-MF from occupational exposures and mortality from neurodegenerative diseases. METHODS: The study was based on a cohort of Swedish engineering industry workers, comprising 537,692 men and 180,529 women. The cohort was matched against the 3 most recent censuses and The Causes of Death Registry. Levels of ELF-MF exposure were obtained by linking occupation according to the censuses to a job exposure matrix. We used 4 levels of exposure and considered both the primary and contributing causes of death, 1985-96. RESULTS: The risk of Alzheimer's disease as primary or contributing cause of death increased with increasing exposure to ELF-MF among both men and women, with a relative risk (RR) of 4.0 and a 95% confidence interval (95% CI) of 1.4-11.7 in the highest exposure group for both sexes combined. There was a RR of 2.2 (95% CI: 1.0-4.7) for ALS in the highest exposure group with the suggestion of an exposure-response relationship. No evidence of increased risk was seen for Parkinson's disease or multiple sclerosis. CONCLUSIONS: The findings support previous observations of an increased risk of Alzheimer's disease and ALS among employees occupationally exposed to ELF-MF. Further studies based on morbidity data are warranted.

Adult↗
PubMed2004

The effect on rat thymocytes of the simultaneous in vivo exposure to 50-Hz electric and magnetic field and to continuous light.

Thymus plays an important role in the immune system and can be modulated by numerous environmental factors, including electromagnetic fields (EMF). The present study has been undertaken with the aim to investigate the role of long-term exposure to extremely low frequency electric and magnetic fields (ELF-EMF) on thymocytes of rats housed in a regular dark/light cycle or under continuous light. Male Sprague-Dawley rats, 2 months old, were exposed or sham exposed for 8 months to 50-Hz sinusoidal EMF at two levels of field strength (1 kV/m, 5 microT and 5 kV/m, 100 microT, respectively). Thymus from adult animals exhibits signs of gradual atrophy mainly due to collagen deposition and fat substitution. This physiological involution may be accelerated by continuous light exposure that induces a massive death of thymocytes. The concurrent exposure to continuous light and to ELF-EMF did not change significantly the rate of mitoses compared to sham-exposed rats, whereas the amount of cell death was significantly increased, also in comparison with animals exposed to EMF in a 12-h dark-light cycle. In conclusion, long-term exposure to ELF-EMF, in animals housed under continuous light, may reinforce the alterations due to a photic stress, suggesting that, in vivo, stress and ELF-EMF exposure can act in synergy determining a more rapid involution of the thymus and might be responsible for an increased susceptibility to the potentially hazardous effects of ELF-EMF.

Animals↗
PubMed2006

Compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations.

We investigated the compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to seven noninfected, catheterized rabbits received 1 mg of amphotericin B deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung tissue were obtained. Pharmacokinetic parameters in plasma were derived by model-independent techniques, and concentrations in ELF and PAM were calculated based on the urea dilution method and macrophage cell volume, respectively. Mean amphotericin B concentrations +/- standard deviations (SD) in lung tissue and PAM were highest in ABLC-treated animals, exceeding concurrent plasma levels by 70- and 375-fold, respectively (in lung tissue, 16.24 +/- 1.62 versus 2.71 +/- 1.22, 6.29 +/- 1.17, and 6.32 +/- 0.57 microg/g for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0029]; in PAM, 89.1 +/- 37.0 versus 8.92 +/- 2.89, 5.43 +/- 1.75, and 7.52 +/- 2.50 mug/ml for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0246]). By comparison, drug concentrations in ELF were much lower than those achieved in lung tissue and PAM. Among the different cohorts, the highest ELF concentrations were found in LAMB-treated animals (2.28 +/- 1.43 versus 0.44 +/- 0.13, 0.68 +/- 0.27, and 0.90 +/- 0.28 microg/ml in DAMB-, ABCD-, and ABLC-treated animals, respectively [P = 0.0070]). In conclusion, amphotericin B and its lipid formulations displayed strikingly different patterns of disposition in lungs 24 h after dosing. Whereas the disposition of ABCD was overall not fundamentally different from that of DAMB, ABLC showed prominent accumulation in lung tissue and PAM, while LAMB achieved the highest concentrations in ELF.

Amphotericin B↗
PubMed1997

Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients.

We studied the penetration of dapsone into the epithelial lining fluid (ELF) of sixteen human immunodeficiency virus type 1-infected patients who had received the drug at a dose of 100 mg twice weekly as primary prophylaxis for Pneumocystis carinii pneumonia. Bronchoscopy, bronchoalveolar lavage (BAL), and venipuncture were performed for each patient at a specific time after administration of the last dose of dapsone. Dapsone concentrations in plasma and BAL were determined by high-performance liquid chromatography. The apparent volume of ELF recovered by BAL was determined by using urea as an endogenous marker. The mean concentrations of dapsone in ELF at 2 h (five patients), 4 h (three patients), 12 h (two patients), 24 h (three patients), and 48 h (three patients) were 0.95, 0.70, 1.55, 0.23, and 0.45 mg/liter, respectively, while concentrations in plasma were 1.23, 0.79, 1.31, 0.83, and 0.18 mg/liter, respectively. Dapsone concentrations in ELF were 76, 79, 115, 65, and 291% of those observed in plasma at the same times, respectively. These data show that dapsone is well distributed into ELF and that a twice-weekly 100-mg prophylactic regimen results in sustained concentrations in this compartment.

Adult↗