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A preliminary study of oscillating electromagnetic field effects on human spermatozoon motility.

Some effects of extremely low frequency electromagnetic fields (ELF-EMFs) on human spermatozoa are reported. Significant increases in the values of the motility and of the other kinematic parameters have been observed when spermatozoa were exposed to an ELF-EMF with a square waveform of 5 mT amplitude and frequency of 50 Hz. By contrast, a 5 mT sine wave (50 Hz) and a 2.5 mT square wave (50 Hz) exposure did not produce any significant effect on sperm motility. The effects induced by ELF-EMF (50 Hz; 5 mT) during the first 3 h of exposure persisted for 21 h after the end of the treatment. These results indicate that ELF-EMF exposure can improve spermatozoa motility and that this effect depends on the field characteristics.

Cells, Cultured↗

Superimposing spatially coherent electromagnetic noise inhibits field-induced abnormalities in developing chick embryos.

Living cells exist in an electrically noisy environment. This has led to the so-called "signal-to-noise" problem whereby cells are observed to respond to extremely-low-frequency (ELF) exogenous fields that are several orders of magnitude weaker than local endogenous fields associated with thermal fluctuations. To resolve this dilemma, we propose that living cells are affected only by electromagnetic fields that are spatially coherent over their surface. The basic idea is that a significant number of receptors must be simultaneously and coherently activated (biological cooperativity) to produce effects on the biochemical functioning of the cell. However, like all physical detection systems, cells are subject to the laws of conventional physics and can be confused by noise. This suggests that a spatially coherent but temporally random noise field superimposed on a coherent ELF signal will defeat the mechanism of discrimination against noise, and any observed field-induced bioeffects would be suppressed. An experimental test of this idea was conducted using morphological abnormalities in developing chick embryos caused by electromagnetic field exposure as the endpoint. At an impressed noise amplitude comparable to the ELF field strength (but roughly one-thousandth of the thermal noise field), the increased abnormality rate observed with only the ELF field present was reduced to a level essentially the same as for the control embryos.

Abnormalities, Radiation-Induced↗

3T3 cell motility and morphology before, during, and after exposure to extremely-low-frequency magnetic fields.

Automated image cytometry techniques were used to measure motility and morphology in 3T3 fibroblasts exposed to extremely-low-frequency (ELF) magnetic fields. Cell motility and morphology were measured as a function of time before, during, and after 3-4 hour exposures to vertically oriented, 100 microTRMS sinusoidal magnetic fields at various frequencies in the 10-63 Hz range. Sham exposures were also carried out. No static DC fields were applied, but the geomagnetic field was almost vertical and, therefore, had a large component (28.3 microT) parallel to the applied AC field. The morphology and motile behavior of the cells were characterized by mathematically defined descriptors, which were calculated and averaged for the exposure period as well as for control periods that preceded and followed the exposure period. Each experiment involved the tracking of 100 cells that were subjected to one of the test frequencies (unless a sham exposure was being conducted). Statistical analysis of the results showed that even small changes of 10-20% could be significant at the P < .05 level. Changes on this order were measured in a significant proportion of the experiments. However, because such results were seen for both the sham-exposed and the ELF-exposed cells, and because the range of values that was obtained for the sham exposures was the same as that obtained for the ELF exposures, we concluded that there was no evidence to show that any of the measured changes were attributable to the applied ELF magnetic field.

3T3 Cells↗

Electromagnetic fields and cells.

There is strong public interest in the possibility of health effects associated with exposure to extremely low frequency (elf) electromagnetic (EM) fields. Epidemiological studies suggest a probable, but controversial, link between exposure to elf EM fields and increased incidence of some cancers in both children and adults. There are hundreds of scientific studies that have tested the effects of elf EM fields on cells and whole animals. A growing number of reports show that exposure to elf EM fields can produce a large array of effects on cells. Of interest is an increase in specific transcripts in cultured cells exposed to EM fields. The interaction mechanism with cells, however, remains elusive. Evidence is presented for a model based on cell surface interactions with EM fields.

Animals↗

Inhibition of gap junction intercellular communication by extremely low-frequency electromagnetic fields in osteoblast-like models is dependent on cell differentiation.

Electromagnetic fields have been used to augment the healing of fractures because of its ability to increase new bone formation. The mechanism of how electromagnetic fields can promote new bone formation is unknown, although the interaction of electromagnetic fields with components of the plasma membrane of cells has been hypothesized to occur in bone cells. Gap junctions occur among bone forming cells, the osteoblasts, and have been hypothesized to play a role in new bone formation. Thus it was investigated whether extremely low-frequency (ELF) magnetic fields alter gap junction intercellular communication in the pre-osteoblastic model, MC3T3-E1, and the well-differentiated osteoblastic model, ROS 17/2.8. ELF magnetic field exposure systems were designed to be used for an inverted microscope stage and for a tissue culture incubator. Using these systems, it was found that magnetic fields over a frequency range from 30 to 120 Hz and field intensities up to 12.5 G dose dependently decreased gap junction intercellular communication in MC3T3-E1 cells during their proliferative phase of development. The total amount of connexin 43 protein and the distribution of connexin 43 gap junction protein between cytoplasmic and plasma membrane pools were unaltered by treatment with ELF magnetic fields. Cytosolic calcium ([Ca(2+)](i)) which can inhibit gap junction communication, was not altered by magnetic field exposure. Identical exposure conditions did not affect gap junction communication in the ROS 17/2.8 cell line and when MC3T3-E1 cells were more differentiated. Thus ELF magnetic fields may affect only less differentiated or pre-osteoblasts and not fully differentiated osteoblasts. Consequently, electromagnetic fields may aid in the repair of bone by effects exerted only on osteoprogenitor or pre-osteoblasts.

Animals↗

Peptide inhibitor of interleukin-8 (IL-8) reduces staphylococcal enterotoxin-A (SEA) induced neutrophil trafficking to the lung.

Staphylococcal enterotoxin A (SEA) is a superantigen, produced by some strains of Staphylococcus aureus (S. aureus), which can cause a variety of clinical manifestations ranging from food poisoning to shock. SEA can also stimulate human alveolar macrophages to produce interleukin-8 (IL-8), a member of the alpha-chemokine subfamily that activates and is chemotactic for neutrophils. In these studies we showed that in rabbits, intravenous SEA significantly decreased the circulating white blood cell population from a baseline value of 6409 +/- 2027 x 10(3) cells/ml to 1943 +/- 862 x 10(3) cells/ml in 7 h. There was a concommitent increase in IL-8 in the circulating plasma (baseline: 60 +/- 34 pg/ml, 7 h post SEA: 109 +/- 64 pg/ml). The increase in circulating IL-8 was accompanied by a much greater increase in the IL-8 concentration of the epithelial lining fluid (ELF) where the IL-8 increased from 0.05 +/- 0.08 ng/ml (control) to 13.8 +/- 9.3 ng/ml (SEA treated). The increase in IL-8 concentration in the alveolar spaces was paralleled by an increase in both the percentage of neutrophils (1.4 +/- 0.9% (control) to 26.0 +/- 10.8% (SEA treated)) and total number of neutrophils (0.04 +/- 0.02 x 10(6)/ml (control) to 4.8 +/- 3.3 10(6)/ml (SEA treated) in the airspaces, and the numbers of neutrophils in the ELF correlated with the IL-8 concentration r = 0.62, p = 0.006). When antileukinate, a hexapeptide which inhibits the binding of IL-8 to neutrophils, was administered to animals receiving SEA, the IL-8 concentration in the ELF (14.8 +/- 10.7 ng/ml) was not significantly different from the concentration of IL-8 in those animals receiving SEA alone). However, both the percentage of neutrophils (9.5 +/- 3.2%), and the total number of neutrophils (1.3 +/- 1.0 x 10(6)/ml) in the ELF following SEA and antileukinate administration was significantly lower than in animals which only received SEA (p < 0.05). The findings suggest that SEA released into the circulation during a Staphylococcal infection can cause an inflammatory reaction in the lung. Since this reaction is at least partially mediated by IL-8, antileukinate may have pharmacologic potential in reducing the inflammatory reaction.

Animals↗

Toxic oxidant species and their impact on the pulmonary surfactant system.

In this review the effects of oxidant inhalation on the pulmonary surfactant system of laboratory animals are discussed. Oxidant lung injury is a complex phenomenon with many aspects. Inhaled oxidants interact primarily with the epithelial lining fluid (ELF), a thin layer covering the epithelial cells of the lung which contains surfactant and antioxidants. In the upper airways this layer is thick and contains high levels of antioxidants. Therefore oxidant injury in this area is rare and is more common in the lower airways where the ELF is thin and contains fewer antioxidants. In the ELF oxidants can react with antioxidants or biomolecules, resulting in inactivation of the biomolecules or in the formation of even more reactive agents. Oxidation of extracellular surfactant constituents may impair its function and affect breathing. Oxidized ELF constituents may promote inflammation and edema, which will impair the surfactant system further. Animal species differences in respiratory tract anatomy, ventilatory rate, and antioxidant levels influence susceptibility to oxidants. The oxidant exposure dose dictates injury, subsequent repair processes, and tolerance induction.

Animals↗

Steady-state plasma and intrapulmonary concentrations of piperacillin/tazobactam 4 g/0.5 g administered to critically ill patients with severe nosocomial pneumonia.

OBJECTIVE: To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of piperacillin/tazobactam (P/T) administered to critically ill patients with severe bacterial pneumonia. DESIGN: Prospective, open-label study. SETTING: An intensive care unit and research ward in a university hospital. PATIENTS: Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation. INTERVENTIONS: All subjects received a 30-min intravenous infusion of P/T 4 g/0.5 g every 8 h. The steady-state plasma and ELF concentrations of P/T were determined by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The mean+/-SD steady-state plasma trough, peak, and intermediate concentrations were 8.5+/-4.6 microg/ml, 55.9+/-21.6 microg/ml, and 24.0+/-13.8 microg/ml for piperacillin, and 2.1+/-1.0 microg/ml, 4.8+/-2.1 microg/ml, and 2.4+/-1.2 microg/ml for tazobactam, respectively. The mean+/-SD steady-state intermediate ELF concentrations were 13.6+/-9.4 microg/ml for piperacillin and 2.1+/-1.1 microg/ml for tazobactam, respectively, showing a mean percentage penetration of piperacillin and tazobactam into ELF of 56.8% and 91.3 %, respectively, with a P/T ratio of 6.5:1. CONCLUSION: Our results show that during the treatment of severe nosocomial pneumonia, a regimen of P/T 4 g/0.5 g every 8 h might provide insufficient concentrations into lung tissue to exceed the MIC of many causative pathogens. This suggests that higher doses of P/T should be administered in order to maximize the antibiotic concentration at the site of infection, or that a second antimicrobial agent should be used in association.

Cross Infection↗

Steady-state trough serum and epithelial lining fluid concentrations of teicoplanin 12 mg/kg per day in patients with ventilator-associated pneumonia.

OBJECTIVE: To determine the steady-state trough serum and epithelial lining fluid (ELF) concentrations of teicoplanin 12 mg/kg per day in critically ill patients with ventilator associated pneumonia. DESIGN AND SETTING: Prospective, pharmacokinetic study in the surgical intensive care unit in a university hospital. PATIENTS: Thirteen adult patients with nosocomial bacterial pneumonia on mechanical ventilation were enrolled. INTERVENTIONS: All subjects received a 30-min intravenous infusion of 12 mg/kg teicoplanin every 12 h for 2 consecutive days followed by 12 mg/kg once daily. Teicoplanin concentrations in serum and ELF were determined simultaneously 4-6 days after antibiotic administration started. MEASUREMENTS AND RESULTS: The median total and free concentrations of teicoplanin in serum at trough were 15.9 microg/ml (range 8.8-29.9) and 3.7 (2.0-5.4), respectively. The concentration in ELF was 4.9 (2.0-11.8). CONCLUSIONS: In critically ill patients with ventilator-associated pneumonia the administration of high teicoplanin doses is required to reach sufficient trough antibiotic concentrations in lung tissues at steady state. At that time trough-free concentrations of teicoplanin in serum and ELF are comparable.

Adolescent↗

Exposure to extremely-low-frequency electromagnetic fields and radiofrequency radiation: cardiovascular effects in humans.

Cardiovascular changes in humans exposed to nonionizing radiation [including extremely-low-frequency electromagnetic fields (ELF EMFs) and radiofrequency radiation (RFR)] are reviewed. Both acute and long-term effects have been investigated. In general, if heating does not occur during exposure, current flow appears to be necessary for major cardiovascular effects to ensue, such as those due to electric shock. Whereas most studies have revealed no acute effect of static or time-varying ELF EMFs on the blood pressure, heart rate, or electrocardiogram waveform, others have reported subtle effects on the heart rate. The possible health consequences of these results are unknown. Regarding long-term effects of ELF EMFs, reports from the former Soviet Union in the early 1960s indicated arrhythmias and tachycardia in high-voltage-switchyard workers. Subsequent studies in Western countries, however, did not confirm these findings. These studies are limited by uncertainties regarding exposure durations and appropriate control groups. Investigations of acute cardiovascular changes in humans purposely exposed to RFR have been limited to studies of magnetic resonance imaging (which, in addition to RFR, involves static and time-varying magnetic fields). It has been concluded that such exposures, as presently performed, are not likely to cause adverse cardiovascular effects. Reports of hypertension in workers potentially exposed to high levels of RFR during accidents are considered to be incidental (due to anxiety and posttraumatic stress). Soviet investigators have also indicated that long-term RFR exposure may result in hypotension and bradycardia or tachycardia. Other researchers, however, have been incapable of replicating these results, and some scientists have attributed the effects to chance variations and mishandling of data. In summary, studies have not yielded any obvious cardiovascular-related hazards of acute or long-term exposures to ELF EMFs or RFR at levels below current exposure standards.

Animals↗

Further evidence for oxidant-induced vascular endothelial growth factor up-regulation in the bronchoalveolar lavage fluid of lung cancer patients undergoing radio-chemotherapy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of physiological and neoplastic blood vessel growth. Moreover, in vitro studies have demonstrated that VEGF can be up-regulated by conditions associated with the generation of free radicals and reactive oxygen species. In a previous study we reported on strongly increased VEGF concentrations in the bronchoalveolar lavage fluid (BALF) of patients with lung cancer under therapy. In this study we aimed to reveal whether this increase was due to the therapy-associated intrapulmonary oxidative burden. PATIENTS AND METHODS: A total of 103 BALF samples from 94 patients with lung cancer (82 patients with non-small-cell lung cancer, 12 patients with small-cell lung cancer) were studied at different times before, during or after cancer treatment. VEGF levels in the lavage fluid and ratios of oxidised methionine in proteins of epithelial lining fluid (ELF) were determined. RESULTS: As reported previously, strongly increased VEGF levels in the ELF were observed in patients undergoing chemotherapy when radiotherapy had been administered before. Increased levels of oxidised methionine indicated that these patients suffered from severe pulmonary oxidative stress that was significantly less in patients undergoing only chemotherapy. Similarly, VEGF concentrations in the ELF were significantly elevated in cancer patients at the time of diagnosis, but the oxidised methionine levels did not reveal significant oxidant/antioxidant imbalances in these patients. CONCLUSION: Systemic chemotherapy is associated with oxidative stress in vivo, which is more pronounced if patients are additionally treated with radiation. VEGF levels in the ELF are increased by this condition as well as by the activity of the tumour itself.

Adult↗

Comparative penetration of selected fluoroquinolones into respiratory tract fluids and tissues.

Sputum samples are easy to obtain; however, their use in therapeutic decision making is not without problems. Today, with the availability of more sophisticated endoscopic procedures, it is possible to determine antimicrobial concentrations at various sites within the respiratory tract. Fiber-optic bronchoscopy makes it possible to obtain samples of bronchial mucosa, bronchial epithelial lining fluid (ELF), and alveolar macrophages (AMs). Antimicrobial concentration measurements from the bronchial mucosa, ELF, and AM may be better predictors of successful antimicrobial therapy than sputum samples. In general, fluoroquinolones penetrate well into lung tissue, including bronchial mucosa, ELF, and AM, resulting in concentrations higher than corresponding serum levels. Temafloxacin, a new fluoroquinolone, attains high bronchial concentrations that are well above the 90% minimal inhibitory concentration (MIC90) for many of the common respiratory pathogens, including Streptococcus pneumoniae (MIC90 = 0.5 micrograms/mL). Early clinical trials confirm the clinical efficacy and safety of temafloxacin in the treatment of many common respiratory tract infections. The penetration of temafloxacin into the bronchial mucosa, AM, and ELF along with its antimicrobial spectrum supports the use of temafloxacin against common respiratory pathogens, including S. pneumoniae.

Anti-Infective Agents↗

Aerosol alpha 1-antitrypsin treatment for cystic fibrosis.

In cystic fibrosis neutrophil-dominated inflammation on the respiratory epithelial surface results in a chronic epithelial burden of the destructive enzyme, neutrophil elastase. alpha 1-antitrypsin (alpha 1AT), the main inhibitor of neutrophil elastase in lung, was given in aerosol form to 12 cystic fibrosis patients. It suppressed neutrophil elastase in the respiratory epithelial lining fluid (ELF) and restored the ELF anti-neutrophil elastase capacity when ELF alpha 1AT reached 8 mumol/l. This treatment also reversed the inhibitory effect of cystic fibrosis ELF on pseudomonas killing by neutrophils, which suggests that it may augment host defence in cystic fibrosis.

Adult↗

A critical review of the genotoxic potential of electric and magnetic fields.

55 published articles were identified which reported results of tests of ELF (extremely low frequency) or static electric or magnetic fields for genotoxic effects. The biological assays used spanned a wide range, including microbial systems, plants, Drosophila, mammalian and human cells in vitro and in vivo. Experimental results were grouped into four exposure categories: ELF Electric; ELF Magnetic; Static Electric; and Static Magnetic. The internal electric fields present in media (for in vitro experiments) and in the torso and extremities (for in vivo experiments) were estimated, providing an index of comparison. All experiments were critically analyzed with respect to basic data quality criteria. Experiments within each exposure category were then compared to determine if results reinforced or contradicted one another. The preponderance of evidence suggests that neither ELF nor static electric or magnetic fields have a clearly demonstrated potential to cause genotoxic effects. However, there may be genotoxic activity from exposure under conditions where phenomena auxiliary to an electric field, such as spark discharges, electrical shocks, or corona can occur. In addition, two unconfirmed reports suggest the genotoxic potential of certain chemical mutagens or ionizing radiation may be affected by co-exposure to electric or magnetic fields. Certain exposure categories are not represented or are under-represented by tests in some genotoxicity test systems that are usually included in minimal test batteries as specified by EPA for chemicals. It is suggested that consideration be given to whether additional genotoxicity testing is warranted to fill these gaps.

Animals↗

Spectroscopic translation of cell-material interactions.

The characterization of cellular interactions with a biomaterial surface is important to the development of novel biomaterials. Traditional methods used to characterize processes such as cellular adhesion and differentiation on biomaterials can be time consuming, and destructive, and are not amenable to quantitative assessment in situ. As the development of novel biomaterials shifts towards small-scale, combinatorial, and high throughput approaches, new techniques will be required to rapidly screen and characterize cell/biomaterial interactions. Towards this goal, we assessed the feasibility of using 4-dimensional elastic light-scattering fingerprinting (4D-ELF) to describe the differentiation of human aortic smooth muscle cells (HASMCs), as well as the adhesion, and apoptotic processes of human aortic endothelial cells (HAECs), in a quantitative and non-perturbing manner. HASMC and HAEC were cultured under conditions to induce cell differentiation, attachment, and apoptosis which were evaluated via immunohistochemistry, microscopy, biochemistry, and 4D-ELF. The results show that 4D-ELF detected changes in the size distributions of subcellular organelles and structures that were associated with these specific cellular processes. 4D-ELF is a novel way to assess cell phenotype, strength of adhesion, and the onset of apoptosis on a biomaterial surface and could potentially be used as a rapid and quantitative screening tool to provide a more in-depth understanding of cell/biomaterial interactions.

Biocompatible Materials↗

Are environmental electromagnetic fields genotoxic?

Long-term exposure to extremely-low-frequency electromagnetic fields (ELF EMFs) greater than 0.4 microT has been linked, by epidemiological studies, to a small elevated risk of childhood leukaemia. Laboratory-based experiments have been claimed to show that ELF EMFs induce a variety of biological responses, although these claims are controversial. Recent experiments by Ivancsits et al. [Mutat. Res. 519 (2002) 1; Int. Arch. Occup. Environ. Health 76 (2003) 431; Mech. Age. Dev. 124 (2003) 847; H.W. Rüdiger, S. Ivancsits, E. Diem, O. Jahn, Genotoxic effects of ELF-EMF on human cells in vitro, Bioelectromagnetics Society 25th Annual Meeting, Maui, USA, 2003] suggest that ELF EMFs are genotoxic, on the basis of observations that intermittent exposures induce single-strand breaks (SSB) and double-strand DNA breaks (DSB) in the DNA of cultured human fibroblasts. The implications of these findings are discussed.

Animals↗

Chromosomal damage in human diploid fibroblasts by intermittent exposure to extremely low-frequency electromagnetic fields.

Environmental exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) has been implicated in the development of cancer in humans. An important basis for assessing a potential cancer risk due to ELF-EMF exposure is knowledge of biological effects on human cells at the chromosomal level. Therefore, we investigated in the present study the effect of intermittent ELF electromagnetic fields (50 Hz, sinusoidal, 5'field-on/10'field-off, 2-24 h, 1 mT) on the induction of micronuclei (MN) and chromosomal aberrations in cultured human fibroblasts. ELF-EMF radiation resulted in a time-dependent increase of micronuclei, which became significant after 10 h of intermittent exposure at a flux density of 1 mT. After approximately 15 h a constant level of micronuclei of about three times the basal level was reached. In addition, chromosomal aberrations were increased up to 10-fold above basal levels. Our data strongly indicate a clastogenic potential of intermittent low-frequency electromagnetic fields, which may lead to considerable chromosomal damage in dividing cells.

Cells, Cultured↗

Microsatellite analysis for determination of the mutagenicity of extremely low-frequency electromagnetic fields and ionising radiation in vitro.

Extremely low-frequency electromagnetic fields (ELF-EMF) have been reported to induce lesions in DNA and to enhance the mutagenicity of ionising radiation. However, the significance of these findings is uncertain because the determination of the carcinogenic potential of EMFs has largely been based on investigations of large chromosomal aberrations. Using a more sensitive method of detecting DNA damage involving microsatellite sequences, we observed that exposure of UVW human glioma cells to ELF-EMF alone at a field strength of 1 mT (50 Hz) for 12 h gave rise to 0.011 mutations/locus/cell. This was equivalent to a 3.75-fold increase in mutation induction compared with unexposed controls. Furthermore, ELF-EMF increased the mutagenic capacity of 0.3 and 3 Gy gamma-irradiation by factors of 2.6 and 2.75, respectively. These results suggest not only that ELF-EMF is mutagenic as a single agent but also that it can potentiate the mutagenicity of ionising radiation. Treatment with 0.3 Gy induced more than 10 times more mutations per unit dose than irradiation with 3 Gy, indicating hypermutability at low dose.

Base Sequence↗