Interference of low frequency magnetic fields with implantable cardioverter-defibrillators

Abstract Objectives. The aim of this study was to find the electromagnetic interference (EMI) thresholds for several commonly used implantable cardioverter-defibrillators (ICD). Design. Seventeen ICDs were exposed to magnetic fields with different intensities produced by the Helmholtz coil system. Sinusoidal, pulse, ramp, and square-waveforms with a frequency range of 2 Hz to 1 kHz were used. Results. ICD malfunctions occurred in 11 of the 17 ICDs tested. The ICD malfunctions that occurred were false detections of ventricular tachycardia (6/17 ICDs) and ventricular fibrillation (3/17 ICDs), false detection of atrial tachycardia (4/6 dual chamber ICDs) and tachycardia sensing occurring during atrial or ventricular refractory periods (1/17 ICD). In most cases, no interference occurred at magnetic field levels below the occupational safety limits of the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Nevertheless, some frequencies using sine, ramp or square waveforms did interfere with certain ICDs at levels below these limits. No EMI occurred with any of the ICDs below the ICNIRP limits for public exposure. Conclusion. Evaluation of EMI should be part of the risk assessment of an employee returning to work after an ICD implantation. The risk assessment should consider magnetic field intensities, frequencies and waveforms.     

Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells

We have previously shown that the G protein-coupled receptor (GPR)30 is critical for progestin-induced growth inhibition. In this study, we addressed signal transduction pathways involved in progestin-mediated signaling. Progestin could not provide any additional growth inhibitory effect to MCF-7 cells treated with specific MAPK kinase inhibitors, PD98059 and U0126. Medroxyprogesteroneacetate (MPA) induced a late (22-23 h) decrease in ERK-1 and -2 activities verified by immunoblotting and kinase assay. The inactivation was abrogated by antiprogestin. Transient expression of GPR30 decreased ERK-1 and -2 activity; and in the cells in which GPR30 expression was decreased by the antisense, ERK activities were increased. The antisense-expressing cells were able to significantly resist the growth-inhibitory effect of the MAPK kinase inhibitors PD98059 and U0126 but not that of other factors tested. Interestingly, the decrease of ERK activity induced by MPA was abrogated by GPR30 antisense. Collectively, these results show that MAPK activity is inhibited by progestin and GPR30 and suggest that progestin-induced ERK inactivation is mediated through GPR30. Coupled with our previous findings, the data imply that up-regulation of GPR30 by progestin leads to ERK-1 and -2 inactivation associated with MPA-induced growth inhibition.     

Estrogen replacement therapy in combination with continuous intrauterine progestin administration reduces the amount of circulating oxidized LDL in postmenopausal women: dependence on the dose of progestin

BACKGROUND. Oxidized low density lipoprotein (LDL) plays a key role in processes leading to atherosclerosis. Recent studies show that LDL oxidation in vitro is effectively prevented by estrogen. Yet, the effect of hormonal therapy (HT) on in vivo LDL oxidation has remained open.

AIM. We used a novel methodology for the measurement of oxidized LDL in vivo in order to investigate the effects of HT.

METHODS. The subjects were derived from two separate trials. In trial 1 (24 months) women (n?=?32) used intrauterine system releasing 10?μg/day levonorgestrel, and 2?mg oral estradiol. Trial 2 (12 months) consisted of two groups of subjects. One group (n?=?30) used an intrauterine system releasing 20?μg/day levonorgestrel, and 2?mg estradiol; the other group (n?=?32) received orally a combination of 1?mg norethisterone acetate and 2?mg estradiol. Blood samples were taken at 6 months intervals. Estimation of in vivo LDL oxidation was based on determination of baseline diene conjugation in isolated LDL.

RESULTS. Hormonal therapy in trial 1 decreased markedly in vivo LDL oxidation. The effect was seen after 6 months' HT and became more pronounced towards the end of study (41% decrease; P?<?0.0001). Contrary to this, in trial 2 the two different kinds of hormonal therapy schemes did not affect in vivo LDL oxidation.

CONCLUSIONS. The strong effect seen in trial 1 shows that intrauterine levonorgestrel with 2?mg estradiol can lower LDL oxidation in vivo. The results show that this effect depends on dosage of the progestin.     

Localization and ontogeny of the orphan receptor OR-1 in the rat brain

This study describes the expression of the OR-1 orphan receptor in embryonic, postnatal, and adult brain tissue studied byin situ hybridization. This newly characterized member of the nuclear receptor superfamily functions as a modulator of retinoic acid and thyroid hormone signalling by influencing gene activation by these hormones from a distinct promoter region. In the fetal brain OR-1 mRNA was observed from E13–E16 in the developing pons, tegmentum, pontine flexure, medulla, inferior and superior colliculi, cerebellum, hippocampus, thalamus, striatum, and cortical plate. At E18, OR-1 was expressed in the hippocampus, cerebellum, ventricular layer of the developing cortex and cortical plate, striatum, and olfactory bulb. In the E21 to early postnatal brain the highest expression of OR-1 mRNA was seen in the hippocampus, cerebellum, striatum, and olfactory bulb. The expression of OR-1 in the cerebellum increased during postnatal development and by d P21 OR-1 mRNA had reached the levels present in the adult in the cerebellar cortex. In the adult brain the highest expression of OR-1 mRNA was observed in the Ca1 area of the hippocampus and the cerebellar cortex. We conclude that OR-1 is widely expressed in the fetal brain, whereas in the postnatal and adult brains OR-1 mRNA is more discretely localized, and that the amount of OR-1 mRNA increases in the cerebellum during postnatal development. The results of this study suggest that, in the fetal brain, OR-1 has a spatially widespread role in modulating gene activation by retinoids and thyroid hormone, whereas in the adult brain this modulation occurs only in distinct neuronal populations.