Targeting of temozolomide using magnetic nanobeads: an in vitro study

Temozolomide, a chemotherapeutic drug that is often administered for the treatment of brain cancer has severe side effects and a poor aqueous solubility. In order to decrease the detrimental effect of the drug over healthy cells, a novel drug delivery vehicle was developed where the therapeutic drug was encapsulated within the hydrophobic cavities of b-CD modified magnetite nanoparticles, which are embedded in chitosan nanobeads prepared by salt addition. In-vitro studies have shown that the magnetic properties of the novel delivery vehicle are adequate for targeted drug delivery applications under an external magnetic field. Additionally, an increase in the amount of chitosan was shown to exhibit a strong shielding effect over the magnetic properties of the delivery vehicle, which lead to deterioration of the amount of captured drug at the targeted area, suggesting a delicate balance between the amounts of constituents composing the drug delivery vehicle.

Turning on stem cell cardiogenesis with extremely low frequency magnetic fields.

Modulation of stem cell differentiation is an important assignment for cellular engineering. Embryonic stem (ES) cells can differentiate into cardiomyocytes, but the efficiency is typically low. Here, we show that exposure of mouse ES cells to extremely low frequency magnetic fields triggered the expression of GATA-4 and Nkx-2.5, acting as cardiac lineage-promoting genes in different animal species, including humans. Magnetic fields also enhanced prodynorphin gene expression, and the synthesis and secretion of dynorphin B, an endorphin playing a major role in cardiogenesis. These effects occurred at the transcriptional level and ultimately ensued into a remarkable increase in the yield of ES-derived cardiomyocytes. These results demonstrate the potential use of magnetic fields for modifying the gene program of cardiac differentiation in ES cells without the aid of gene transfer technologies and may pave the way for novel approaches in tissue engineering and cell therapy.

Magnetic retention in prosthetic dentistry.

Magnets are a popular method of attaching removable prostheses to either retained roots or osseointegrated implants. This paper reviews the development of magnets in dentistry and describes the different types of magnetic attachments that are available. The clinical applications of magnets in prosthetic dentistry are illustrated and future technological advancements indicated. Whilst different magnetic materials that mirrored the developing technology have been used, the main drawback to their use is the potential of corrosion of the magnetic material in the mouth. However, newly emerging technologies may provide a solution to this problem, allowing the continued use of magnets in prosthetic dentistry.

Coronary heart diseases: assessment of risk associated with work exposure to ultralow-frequency magnetic fields.

The present analysis was stimulated by previous findings on the possible influence of natural ultralow-frequency (ULF; 0.001-10 Hz) geomagnetic field variations on the cardiovascular system and indications of an effect of man-made ULF magnetic fields on the rate of myocardial infarction. In the present study, we considered the occupational health hazards of the strongest ULF magnetic fields in densely populated urban areas. Measurements of ULF magnetic field fluctuations produced by trains powered by DC electricity were performed by means of a computer-based, highly sensitive, three-component magnetometer. We found that the magnitude of magnetic field pulses inside the driver's cab of electric locomotives (ELs) could be > or = 280 microT in the horizontal component perpendicular to the rails and up to approximately 130 microT in the vertical component, and, in the driver's compartment of electric motor unit (EMU) trains, they were approximately 50 and 35 microT, respectively. We have investigated the relationships between the occupational exposure to ULF magnetic field fluctuations produced by electric trains and cardiovascular diseases (CVDs) among railroad workers in the former Soviet Union. We have analyzed medical statistical data for a period of 3 years for approximately 45,000 railroad workers and 4,000 engine drivers. We have also analyzed 3 years of morbidity data for three subgroups of engine drivers (approximately 4,000 in each group) operating different types of trains. We find that EL drivers have a twofold increase in risk (2.00 +/- 0.27) of coronary heart diseases (CHDs) compared with EMU drivers. Because our analysis of major CVDs shows that the examined subpopulations of drivers can be considered to have had equal exposure to all known risk factors, the elevated CHD risk among EL drivers could be attributed to the increased occupational exposure to ULF magnetic fields.

Weak extremely-low-frequency magnetic field-induced regeneration anomalies in the planarian Dugesia tigrina.

We recently reported that cephalic regeneration in the planarian Dugesia tigrina was significantly delayed in populations exposed continuously to combined parallel DC and AC magnetic fields. This effect was consistent with hypotheses suggesting an underlying resonance phenomenon. We report here, in a parallel series of investigations on the same model system, that the incidence of regeneration anomalies presenting as tumor-like protuberances also increases significantly (P < .001) in association with exposure to weak 60 Hz magnetic fields, with peak intensities ranging between 1.0 and 80.0 microT. These anomalies often culminate in the complete disaggregation of the organism. Similar to regeneration rate effects, the incidence of regeneration anomalies is specifically dependent upon the planaria possessing a fixed orientation with respect to the applied magnetic field vectors. However, unlike the regeneration rate effects, the AC magnetic field alone, in the absence of any measurable DC field, is capable of producing these anomalies. Moreover, the incidence of regeneration anomalies follows a clear dose-response relationship as a function of AC magnetic field intensity, with the threshold for induced electric field intensity estimated at 5 microV/m. The addition of either 51.1 or 78.4 microT DC magnetic fields, applied in parallel combination with the AC field, enhances the appearance of anomalies relative to the 60 Hz AC field alone, but only at certain AC field intensities. Thus, whereas our previous study of regeneration rate effects appeared to involve exclusively resonance interactions, the regeneration anomalies reported here appear to result primarily from Faraday induction coupling. These results together with those reported previously point to two distinct physiological effects produced in regenerating planaria by exposure to weak extremely-low-frequency (ELF) magnetic fields. They further suggest that the planarian, which has recently been identified elsewhere as an excellent system for use in teratogenic investigations involving chemical teratogens, might be used similarly in teratogenic investigations involving ELF magnetic fields.

Measurements described in a paper by Blackman, Blanchard, Benane, and House are statistically invalid.

Blackman et al. [1994] describe an experiment that purports to show that weak 45 Hz magnetic fields inhibit the growth of neurites from PC-12 cells treated with a growth stimulation factor. I present a statistical analysis of the data in that paper that shows that the data were corrupted in some way; hence, the results are invalid.

No effect of exposure to static and sinusoidal magnetic fields on nitric oxide production by macrophages.

The effects of exposure to static (1 - 100 mT) or sinusoidal (1 Hz, 1.6 mT) magnetic fields on the production of nitric oxide (NO) by murine BCG-activated macrophages were investigated. In these cells, the inducible isoform of NO synthase is present. No significant differences were observed in nitrite levels among exposed, sham-exposed, or control macrophages after exposure for 14 h to static fields of 1, 10, 50, and 100 mT and to sinusoidal 1.6 mT, 1 Hz magnetic fields.

Nonbinomial distribution of relative neurite outgrowth in PC-12 cells.

Previously we reported the results of a series of experimental tests using PC-12 cells to examine the biological effect of prescribed combinations of both nerve growth factor and magnetic fields. Because our assay of the PC-12 cells is based on binary classification of the cells following treatment, our data might be expected to have a binomial distribution. However, our data consistently show a smaller variability than that predicted by the binomial distribution model. In this paper, we examine some possible reasons for this reduction in variability in our results.

Weak extremely-low-frequency magnetic fields and regeneration in the planarian Dugesia tigrina.

Extremely-low-frequency (ELF), low-intensity magnetic fields have been shown to influence cell signaling processes in a variety of systems, both in vivo and in vitro. Similar effects have been demonstrated for nervous system development and neurite outgrowth. We report that regeneration in planaria, which incorporates many of these processes, is also affected by ELF magnetic fields. The rate of cephalic regeneration, reflected by the mean regeneration time (MRT), for planaria populations regenerating under continuous exposure to combined DC (78.4 muT) and AC (60.0 Hz at 10.0 muTpeak) magnetic fields applied in parallel was found to be significantly delayed (P << 0.001) by 48 +/- 1 h relative to two different types of control populations (MRT approximately 140 +/- 12 h). One control population was exposed to only the AC component of this field combination, while the other experienced only the ambient geomagnetic field. All measurements were conducted in a low-gradient, low-noise magnetics laboratory under well-maintained temperature conditions. This delay in regeneration was shown to be dependent on the planaria having a fixed orientation with respect to the magnetic field vectors. Results also indicate that this orientation-dependent transduction process does not result from Faraday induction but is consistent with a Ca2+ cyclotron resonance mechanism. Data interpretation also permits the tentative conclusion that the effect results from an inhibition of events at an early stage in the regeneration process before the onset of proliferation and differentiation.

Do ELF magnetic fields affect human reaction time?

Two double-blind studies were run in an attempt to confirm the finding that a 0.2 Hz magnetic field affects simple reaction time (RT) in humans, whereas a 0.1 Hz field does not. In the first experiment, 12 volunteer subjects were exposed to a continuous 0.2 Hz, 0.1 Hz, or sham field in a fully counterbalanced, within-subjects design. Subjects were run singly for one condition each day over 3 consecutive days with a field strength of 1.1 mT and a daily exposure duration of 5 min. Neither magnetic field had any effect on RT at any time during the exposure. One condition of a second study, using a new group of 24 volunteer subjects, also failed to find any field effects at 0.2 Hz. Additionally, the second study failed to show any effects when the frequency, flux density, and field orientation were set according to parametric resonance theory. It is suggested that, although ELF magnetic field effects on human behaviour may be elusive, future research can improve detection rates by paying greater attention to reducing error variance and increasing statistical power.

Chick embryo development can be irreversibly altered by early exposure to weak extremely-low-frequency magnetic fields.

Several reports have shown that weak, extremely-low-frequency (ELF), pulsed magnetic fields (PMFs) can adversely affect the early embryonic development of the chick. In this study, freshly fertilized chicken eggs were exposed during the first 48 h of postlaying incubation to PMFs with 100 Hz repetition rate, 1.0 microT peak-to-peak amplitude, and 500 microseconds pulse duration. Two different pulse waveforms were used, having rise and fall times of 85 microseconds (PMF-A) or 2.1 microseconds (PMF-B). It has been reported that, with 2 day exposure, these fields significantly increase the proportion of developmental abnormalities. In the present study, following exposure, the eggs were allowed to incubate for an additional 9 days in the absence of the PMFs. The embryos were taken out of the eggs and studied blind. Each of the two PMF-exposed groups showed an excess in the percentage of developmental anomalies compared with the respective sham-exposed samples. This excess of anomalies was not significant for the PMF-A-treated embryos (P = 0.173), whereas it was significant for the PMF-B-exposed group (P = 0.007), which showed a particularly high rate of early embryonic death. These results reveal that PMFs can induce irreversible developmental alterations and confirm that the pulse waveform can be a determinant factor in the embryonic response to ELF magnetic fields. The data also validate previous work based on the study of PMFs' effects at day 2 of embryonic development under field exposure.

Temporally incoherent magnetic fields mitigate the response of biological systems to temporally coherent magnetic fields.

We have previously demonstrated that a weak, extremely-low-frequency magnetic field must be coherent for some minimum length of time (approximately 10 s) in order to affect the specific activity of ornithine decarboxylase (ODC) in L929 mouse cells. In this study we explore whether or not the superposition of an incoherent (noise) magnetic field can block the bioeffect of a coherent 60 Hz magnetic field, since the sum of the two fields is incoherent. An experimental test of this idea was conducted using as a biological marker the twofold enhancement of ODC activity found in L929 murine cells after exposure to a 60 Hz, 10 microT rms magnetic field. We superimposed an incoherent magnetic noise field, containing frequencies from 30 to 90 Hz, whose rms amplitude was comparable to that of the 60 Hz field. Under these conditions the ODC activity observed after exposure was equal to control levels. It is concluded that the superposition of incoherent magnetic fields can block the enhancement of ODC activity by a coherent magnetic field if the strength of the incoherent field is equal to or greater than that of the coherent field. When the superimposed, incoherent noise field was reduced in strength, the enhancement of ODC activity by the coherent field increased. Full ODC enhancement was obtained when the rms value of the applied EM noise was less than one-tenth that of the coherent field. These results are discussed in relation to the question of cellular detection of weak EM fields in the presence of endogenous thermal noise fields.

Behavioral sensitivity of rats to extremely-low-frequency magnetic fields.

Work in our laboratory has revealed autonomic and/or behavioral sensitivity of mice, rats, and a domestic fowl to extremely-low-frequency (ELF) or nominally static magnetic (B) fields at flux densities between 250 and 1700 microT (rms). To extend our work, an automated exposure and data-acquisition system was used with the technique of conditional suppression to assess behavioral sensitivity to time-varying B fields. Each of five rats was exposed aperiodically to a B field during 3 min warning periods that terminated in a brief electric shock. The difference between rates of lever pressing during B-field warning periods and rates during immediately antecedent, 3 min control periods was analyzed at frequencies of 7, 16, 30, 60, and 65.1 Hz. To produce equivalent induced voltages in the rat at each frequency, graded flux densities were established that ranged from 1900 microT at 7 Hz to 200 microT at 65.1 Hz. Analysis of differences in lever-pressing rates revealed that in a given session of testing the rats would increasingly suppress responding when exposed to a B field, but this trend was independent of frequency. This experiment provides evidence of behavioral sensitivity by a mammal to an ELF magnetic field.

Magnetic-field flux density and spectral characteristics of motor-driven personal appliances.

Flux density and spectral measurements were carried out on magnetic fields generated by several types of motor-driven personal appliances used near the body. Among the units tested were several for which the average flux densities, as determined at the surfaces of the appliance, exceeded 0.4 mT. Time-rates-of-change (dB/dt) for several units exceeded 1000 T/s, and several units exhibited high-frequency components in the low-MHz range. Use of such appliances, although normally of short duration, can represent exposure to magnetic fields of relatively high flux density, which may also have high-frequency components. Compared to other household and commercial sources of magnetic fields, those generated by certain motor-driven personal appliances may represent a significant contribution to time-weighted average exposure and may represent an important source of local induced currents in the body. Furthermore, high-frequency transients that represent only a minor contribution to time-weighted average exposure may generate significant instantaneous induced currents.