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Electromagnetic fields (1.8 GHz) increase the permeability to sucrose of the blood-brain barrier in vitro

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Abstract

We report an investigation on the influence of high frequency electromagnetic fields (EMF) on the permeability of an in vitro model of the blood-brain barrier (BBB). Our model was a co-culture consisting of rat astrocytes and porcine brain capillary endothelial cells (BCEC). Samples were characterized morphologically by scanning electron microscopy and immunocytochemistry. The BBB phenotype of the BCEC was shown by the presence of zona occludens protein (ZO-1) as a marker for tight junctions and the close contact of the cells together with the absence of intercellular clefts. Permeability measurements using (14)C-sucrose indicated a physiological tightness which correlated with the morphological findings and verified the usefulness of our in vitro model. Samples were exposed to EMF conforming to the GSM1800-standard used in mobile telephones (1.8 GHz). The permeability of the samples was monitored over four days and compared with results of samples that were cultured identically but not exposed to EMF. Exposure to EMF increased permeability for (14)C-sucrose significantly compared to unexposed samples. The underlying pathophysiological mechanism remains to be investigated.

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... No variation of the relative mean fluorescence intensity as a function of time was observed outside the vessels when compared to non-illuminated samples ( Figure 5E). Conversely, dextran leakage is, as expected, observed in the positive control, when permeabilizing electric field (eight square electric pulses, field strength 1300 V/cm, pulse length 100 µs, repetition frequency 1 Hz) is applied, according to the procedure that was previously described [10,11]. ...
... Vessel permeabilization occurred after application of eight square monopolar electric pulses, with a field strength of 1300 V/cm, pulse length 100 µs, and repetition frequency of 1 Hz, generated by an electric pulse generator S20 (Leroy Biotech, Saint-Orens-de-Dameville, France). The pulses were applied as described previously [10,11], with two parallel stainless-steel electrodes (length 5 mm, width 1.3 mm) 4 mm apart, which were placed in contact with the skinfold-containing DWC, on which conductive gel (Eko-gel, Egna, Italy) was spread, to ensure signal transmission between the electrodes. ...
... The files were stored and analyzed offline after image acquisition (Metavue, Metamorph, Molecular Devices, Sunnyvale, CA, USA and software ImageJ, National Institute of Mental Health, Bethesda, MD, USA). The fluorescence intensity outside the blood vessels was determined after image processing as previously described [10,11]. After data processing, variations in fluorescence intensity outside the vessels were obtained. ...
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High power radiofrequencies may transiently or permanently disrupt the functioning of electronic devices, but their effect on living systems remains unknown. With the aim to evaluate the safety and biological effects of narrow-band and wide-band high-power electromagnetic (HPEM) waves, we studied their effects upon exposure of healthy and tumor-bearing mice. In field experiments, the exposure to 1.5 GHz narrow-band electromagnetic fields with the incident amplitude peak value level in the range of 40 kV/m and 150 MHz wide-band electric fields with the amplitude peak value in the range of 200 kV/m, did not alter healthy and tumor-bearing animals’ growth, nor it had any impact on cutaneous murine tumors’ growth. While we did not observe any noticeable behavioral changes in mice during the exposure to narrow-band signals when wide-band HPEM signals were applied, mice could behave in a similar way as they respond to loud noise signals: namely, if a mouse was exploring the cage prior to signal application, it returned to companion mates when wide-band HPEM signals were applied. Moreover, the effect of wide-band signals was assessed on normal blood vessels permeability in real-time in dorsal-chamber-bearing mice exposed in a pilot study using wide-band signal applicators. Our pilot study conducted within the applicator and performed at the laboratory scale suggests that the exposure to wide-band signals with the amplitude of 47.5 kV/m does not result in increased vessel permeability.
... Σε ερευνητικά εργαστήρια κατασκευάστηκαν οµοιώµατα του ανθρώπινου κεφαλιού από υλικά τα οποία έχουν παρόµοιες διηλεκτρικές ιδιότητες µε τα συστατικά του εγκεφάλου. Ένα τέτοιο οµοίωµα είναι και αυτό στην εικόνα 1.2 που ακολουθεί, όπου φαίνεται ένας τρόπος πειραµατικής δοσιµετρίας [15]. εικόνα 1.2 ∆ιάταξη πειραµατικής δοσιµετρίας σε οµοίωµα κεφαλιού µε χρήση κινητού τηλεφώνου. ...
... [14] Mason P. M., Murphy M. R., Petersen R. C., "IEEE EMF Health and Safety Standards". [15] Preece A. W., Iwi G. , Davies-Smith A., Wesnes K., Butler S., Lim E., Varey A. "Effect of a 915 MHz simulated mobile phone signal on cognitive function in man", Int. J. Radiat. ...
... Καλλιέργειες κυττάρων, αστροκύτταρα από ποντίκια και τριχοειδή ενδοθηλιακά κύτταρα από χοιρινά, εκτέθηκαν σε 1800 MHz GSM σήµα [15]. Η διαπερατότητα των κυττάρων αυτών συγκρίνονταν, και τις τέσσερις ηµέρες που διήρκησε η έκθεση, µε τη διαπερατότητα όσων κυττάρων είχαν κρατηθεί ως κύτταρα αναφοράς και δεν εκτέθηκαν. ...
... These findings are in agreement with Takashima et al. [33] who reported a decrease in high frequency EEG bands and an increase in low frequency bands after chronic exposure of the male rabbit to Radiofrequency field. Similarly, acute exposure of rats and rabbits to continuous microwaves increased EEG delta activity [29]. In addition, Chizhenkova [3] reported that the heads of unanesthetized rabbits exposed to 2.4 GHz for 1 min at 40 mW/cm 2 demonstrated EEG spindle-shaped firings and an increase in the number of slow waves. ...
... However, this result emphasizes that the EMF at non-thermal range can have a similar effect as thermal intensity on the electrical activity of the brain. Non-thermal effects of EMF on the nervous system have been reported in several studies [6,25,28,29,32]. Lass et al. [20] and Hinrikus et al. [12] demonstrated the influence of the low-level microwaves on human EEG and mental behavior. ...
Article
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In the present study the effect of long-term exposure (1 hour/day for 4 months) to electromagnetic radiation field (EMF) (900 MHz, 0.02 mW/cm 2 , SAR: 1.165 W/kg) on the EEG of freely moving rat is investigated. The spectral analysis of the EEG bands was done after 1, 2 and 4 months of daily EMF irradiation and after 1 month of stopping irradiation that extended daily for 4 months. The quantitative analysis of EEG revealed a clear shift from high frequency (beta) to lower frequency (delta) in irradiated animals as compared to unexposed animals, which indicated the change in the animal arousal. The cumulative effect of non-thermal EMF has been suggested for chronic exposure to radiation. It could be suggested that EMF cause changes in central cholinergic system that change the cortical excitability that reflected in slowing down of the EEG frequencies.
... Microwaves are found to produce thermally and non-thermally a large number of biological effects, in many cellular and animal studies, (Banik et al, 2003). In the case of radiations emitted by mobile telephony antennas at intensities that people are normally exposed, the effects are non-thermal as verified by different experimenters, (Diem et al, 2005;Panagopoulos et al, 2004;2007a;2007b;Leszczynski et al, 2002;Schirmacher et al, 2000;Velizarov et al, 1999) Regarding non-thermal effects of RF radiations, it is a must to refer to the pioneer works of Bawin et. al. and Blackman et. ...
... W/kg, increased the permeability to sucrose of the BBB twice compared to the control culture. No significant temperature rise was detected during the exposures, (Schirmacher et al, 2000). ...
... The recent results in brain cell damage in mammalian brain and blood-brainbarrier (BBB) permeability confirm that extremely low doses of microwave radiation affect the physiology of the brain [ [17][18][19]. A pathological leakage over the BBB was combined with a damage to the neurones [ 18 ]. ...
... There is no physical reason for that. The reduction of permeability of the myelinated sheath would be opposite to the trend of changes in BBB [ [17][18][19]. Therefore we can suppose that the dependence of the velocity of the nerve pulse propagation on the microwave field is related to the changes in the active membrane of the fibre in the nodes of Ranvier. ...
... Due to the indivisibility of mature neurons, they are not suitable for experiments that require a large number of cells. The primary cultured neurons used in previous studies on microwave radiation bioeffects included primary cortical neurons, hippocampal neurons, and astrocytes [147][148][149][150]. ...
... In addition, several methods, such as albumin immunohistochemistry staining [89,[114][115][116]190], transendothelial electrical resistance (TEER) measurement [38], horseradish peroxidase (HRP) staining method [38], and 14 C-sucrose-tracing methods [148], could also be used to study the effects on BBB permeability induced by microwave radiation. TEER indicates the impedance to pass through the BBB, which is recognized as one of the most accurate and sensitive indicators of BBB integrity [38]. ...
Article
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Microwave radiation has been widely used in various fields, such as communication, industry, medical treatment, and military applications. Microwave radiation may cause injuries to both the structures and functions of various organs, such as the brain, heart, reproductive organs, and endocrine organs, which endanger human health. Therefore, it is both theoretically and clinically important to conduct studies on the biological effects induced by microwave radiation. The successful establishment of injury models is of great importance to the reliability and reproducibility of these studies. In this article, we review the microwave exposure conditions, subjects used to establish injury models, the methods used for the assessment of the injuries, and the indicators implemented to evaluate the success of injury model establishment in studies on biological effects induced by microwave radiation.
... One study by Schirmacher et al used C 14 -labeled sucrose in a mouse-porcine system. The study reported that athermal GSM radiation increased the permeability to sucrose (Schirmacher et al, 2000). This protocol possibly differs from others in that active transport of glucose does not require opening of cell-to-cell contacts. ...
... Notably, in all these studies, the SAR-values for exposure are relatively high; never including the low SAR-values below 200 mW/kg. In more recent years, in vitro models have been increasingly applied to investigate the BBB; in one of these, it was shown that EMFs at 1.8 GHz increase the permeability to sucrose [51]. After modifications of the BBB model to one with higher tightness, however, the same group could not replicate their initial findings [52]. ...
... Although, the biological basis for these sex differences remains elusive, emerging evidence provides plausible mechanisms for the explanation of these differences. In particular, central nervous system effects of EMFs have been considered to be secondary to damage to the blood-brain barrier (BBB) permeability [28][29][30][31].At this point is reasonable to consider the existence of gender-related blood-barrier differences, a fact which would explain the fundamental differences between males and females in the intrinsic cognitive processes and in the way they are affected by different types of electromagnetic radiation [32][33][34]. Furthermore research also indicates that EMF exposure affects the melatonin release, specifically it has been demonstrated a reduced excretion of the urinary metabolite of melatonin among persons using a mobile phone for more than 25 min per day [35]. ...
Article
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Efesiou (PO Box 66 517) Athens, 15601, GREECE, Tel: ++30210-6536902, Fax: ++30210-6537273 Abstract The present study investigated the influence of electromagnetic fields, similar to that emitted by Wi-Fi system, on brain activity. Fifteen female and fifteen male subjects performed a short memory task (Wechsler test), both without and with exposure to a 2.4GHz Wi-Fi signal. For each subject, radiation condition and electrode, the amplitude in the frequency domain of the EEG signal was calculated from the recordings of 30 scalp electrodes, using the Fourier transform. The presence of radiation had no effect on the energies of alpha and beta band of male subjects, while it reduced these energies of female subjects, resulting in significantly lower energies, as compared to those of males. Delta and theta band energies did not experience any noteworthy effect from gender, radiation condition and their interaction. Conversely, there was a significant interaction effect (gender x radiation) on the energies of alpha and beta rhythms. Interestingly, this pattern was observed for a number of electrodes, which formed two distinct clusters . one located at right-anterior and the second at occipital brain areas. The present data support the idea that Wi-Fi signal may influence normal physiology through changes in gender related cortical excitability, as reflected by alpha and beta EEG frequencies. A. MAGANIOTI ET AL.
... Pericytes and endothelial cells are sheathed by the basal lamina, a membrane 30-40-nm thick which is continuous with the plasma membranes of astrocytic end-foot processes, which sheath the cerebral capillaries (Hawkins & Davis, 2005). The plasma bilayer is high in cholesterol, which allows for a high packing density of membrane components; therefore, the resistance to passive diffusion of large lipophilic molecules is greater compared to that of noncerebral capillaries (Schirmacher et al., 2000). As well as preventing the entry of solutes into the brain from the blood, the BBB does not allow free diffusional movement of solutes out of the CNS either, hindering free diffusion in a bidirectional way and restricting movement to transcellular transport (passive diffusion, carrier transport, or endocytotic processes). ...
Chapter
Many brain tumors and neurological diseases can greatly benefit from the use of emerging nanotechnologies based on targeted nanomedicines that are able to noninvasively transport highly potent and specific pharmaceuticals across the blood–brain barrier. Carbohydrates have received considerable interest as materials for drug carriers due to their natural origin and inherent biodegradability and biocompatibility, as well as due to their hydrophilic character and ease of chemical modification combined with low cost and the possibility for large-scale manufacturing. This chapter provides an overview of the latest research involving the use of carbohydrate-based nanoparticles for drug delivery to the central nervous system. After reviewing the challenges posed by delivering drugs into the brain, the current state-of-the-art approaches for delivery of actives across the blood–brain barrier, including invasive and noninvasive strategies, are presented. A particular focus has been placed on chitosan polymers as they are among the most promising carbohydrate nanocarriers for the preparation and testing of chitosan-based nanomedicines that led, in preclinical proof-of-concept studies, to enhanced brain drug levels and increased pharmacodynamics responses after intravenous, nasal, and oral administration. While chitosan nanoparticles are to date among the most studied and most promising carriers, approaches based on other polysaccharides such as dextran, pullulan, and cellulose warrant further research in the attempt to advance the existing technologies for overcoming the blood–brain barrier.
... Kumlin et al. (38) confirmed that 900 MHz radiation have no effect on the BBB permeability of young rats. In vitro models have been increasingly applied to investigate the BBB in last years; in one of these, it was shown that 1.8 GHz exposure increase the permeability to sucrose (39). After modifications of the BBB model to one with higher tightness, however, the same group could not replicate their initial findings (40). ...
Article
Health concerns have been a raised after the enormous increase in the use of mobile phones and related base stations throughout the world. In spite of extensive increase in the studies of biological effects of mobile phone radiations with in last decades, little is known about the effect of long term exposure. In this present report, we summarized a review of the literature on the effects of radio-frequency radiation exposure on the permeability of blood-brain barrier. Gazi University Biophysics group have earlier shown that the electromagnetic radiation emitted by mobile phones – also called radio-frequency radiation - alters the permeability of the blood–brain barrier, GSM like modulated fields were found to be more effective than continuous-wave fields. This paper will review some evidence that demonstrates the existence of non-thermal effects and the exposure complexities that must be considered and understood to provide appropriate, more thorough evaluation and guidance for future studies and for assessment of potential health consequences
... Exposure to electromagnetic radiation has an effect, especially on the user. Although many studies have revealed that microwave radiation exposure has no detrimental effect on human health whatsoever (1)(2)(3)(4)(5)(6), some studies have shown the contrary (7)(8)(9). This study aimed to reveal the effect of 2100 MHz RF radiation on thyroid tissues of rats in the early and late stages. ...
Article
Full-text available
Background: The study aims to reveal the effect of 2100 MHz radio frequency radiation (RF) on thyroid tissues of the rats in early and late groups. Material and method: In this study, 30 healthy female Wistar albino rats, weighting 200 to 256 g each were used. The animals were randomly divided into four groups (groups E1, E2, G1, G2). Groups E2 and G2 served as the control groups. The exposure groups were exposed to 2100 MHz radio frequency radiation emitted by a generator, simulating a 3G-mobile phone for six hours/day, five consecutive days/week, at the same time of the day (between 9 am - 3 pm), for 10 days (group E1) and 40 days (group G1). Results: Catalase and xanthine oxidase enzyme activities were compared between the groups E1 and E2, it was found that the difference was statistically significant (p < 0.05). Between the groups G-1 and G-2 the difference was found to be significant with respect to catalase activities. The early and late groups tissue samples showed no serious pathological findings in the histo-pathological examination. Conclusion: We believe that comprehensive, clinical and experimental studies, are needed to assess how effective the radio frequency (RF) exposure duration and dosage of exposure on thyroid tissues.
... In vivo experiments on BBB permeabilization, such as the ones mentioned above, provide mostly qualitative results, therefore making in vitro models necessary for obtaining more quantitative analysis; however, their physiological relevance is always a matter of debate. Several in vitro models have been previously developed to simulate the integrity and permeability of the BBB to different substances (36,37) as well as investigate the effect of different stimuli such as chemicals (38), pressure shock (39), radiation (40), and electromagnetic fields (41)(42)(43). Microfluidics studies provide an alternative platform to standard in vitro systems for analyzing cells and tissues in a more physiologically relevant environment (44,45). Organs-on-chip platforms utilize the advantages of microfluidics to recreate in vivo conditions of the body in an easily testable, in vitro setting. ...
Article
The blood-brain barrier, mainly composed of brain microvascular endothelial cells, poses an obstacle to drug delivery to the brain. Controlled permeabilization of the constituent brain endothelial cells can result in overcoming this barrier and increasing transcellular transport across it. Electroporation is a biophysical phenomenon that has shown potential in permeabilizing and overcoming this barrier. In this study we developed a microengineered in vitro model to characterize the permeabilization of adhered brain endothelial cells to large molecules in response to applied pulsed electric fields. We found the distribution of affected cells by reversible and irreversible electroporation, and quantified the uptaken amount of naturally impermeable molecules into the cells as a result of applied pulse magnitude and number of pulses. We achieved 81 ± 1.7% (N = 6) electroporated cells with 17 ± 8% (N = 5) cell death using an electric-field magnitude of ∼580 V/cm and 10 pulses. Our results provide the proper range for applied electric-field intensity and number of pulses for safe permeabilization without significantly compromising cell viability. Our results demonstrate that it is possible to permeabilize the endothelial cells of the BBB in a controlled manner, therefore lending to the feasibility of using pulsed electric fields to increase drug transport across the BBB through the transcellular pathway.
... As well as, the reported that 900 MHz EMF's is changed brain blood barrier permeability (Salford et al., 2003;Nittby et al., 2009, Fig. 8). And the other in vitro study investigated that 1.8 GHz EMF is caused increase permeability blood brain barrier to sucrose (Schirmacher et al., 2000). There was an albumin a lot of small foci leakage from the various vessels after the EMF exposure (Salford et al., 2003). ...
... They showed that the combined exposure to RF, pulsed and static magnetic fields gave rise to a significant pinocytotic transport of albumin from the capillaries into the brain. In 2000 an in-vitro study showed that EMF at 1.8 GHz increases the permeability to sucrose of BBB (Schirmacher et al., 2000). Salford's group has studied the effects of 915 MHz RF in a rat model and showed that energies below the thermal level from both pulse-modulated and continuous RF fields, have the potency to significantly open BBB (Salford et al., 1994;Salford 1993;Persson et al., 2003). ...
Article
With the increased use of mobile phones, their biological and health effects have become more important. Usage of mobile phones near the head increases the possibility of effects on brain tissue. This study was designed to investigate the possible effects of pulse modulated 900MHz and 1800MHz radio-frequency radiation on the permeability of blood-brain barrier of rats. Study was performed with 6 groups of young adult male and female wistar albino rats. The permeability of blood-brain barrier to intravenously injected evans blue dye was quantitatively examined for both control and radio-frequency radiarion exposed groups. For male groups; Evans blue content in the whole brain was found to be 0.08±0.01mg% in the control, 0.13±0.03mg% in 900MHz exposed and 0.26±0.05mg% in 1800MHz exposed animals. In both male radio-frequency radiation exposed groups, the permeability of blood-brain barrier found to be increased with respect to the controls (p<0.01). 1800MHz pulse modulated radio-frequency radiation exposure was found more effective on the male animals (p<0.01). For female groups; dye contents in the whole brains were 0.14±0.01mg% in the control, 0.24±0.03mg% in 900MHz exposed and 0.14±0.02mg% in 1800MHz exposed animals. No statistical variance found between the control and 1800MHz exposed animals (p>0.01). However 900MHz pulse modulated radio-frequency exposure was found effective on the permeability of blood-brain barrier of female animals. Results have shown that 20minutes pulse modulated radio-frequency radiation exposure of 900MHz and 1800MHz induces an effect and increases the permeability of blood-brain barrier of male rats. For females, 900MHz was found effective and it could be concluded that this result may due to the physiological differences between female and male animals. The results of this study suggest that mobile phone radation could lead to increase the permeability of blood-brain barrier under non-thermal exposure levels. More studies are needed to demonstrate the mechanisms of that breakdown.
... Earlier studies sometimes suffered from poor dosimetry, that is, magnitude and uniformity of actual cell exposure in terms of specific absorption rate (SAR) was only vaguely described, if at all. In more recent studies, sophisticated and optimized exposure instrumentation based arrangements such as waveguides [Schirmacher et al., 2000;Schuderer et al., 2004], wire patch cells [Laval et al., 2000], waveguide apertures [Gajda et al., 2002], TEM cells [Nikoloski et al., 2005], and others have been used. A comparison of some performance aspects of different setup types can be found in Schönborn et al. [2001] as well as Paffi et al. [2010]. ...
Article
The objective of this paper is to compare realistic maximum electromagnetic exposure of human tissues generated by mobile phones with electromagnetic exposures applied during in vitro experiments to assess potentially adverse effects of electromagnetic exposure in the radiofrequency range. We reviewed 80 in vitro studies published between 2002 and present that concern possible adverse effects of exposure to mobile phones operating in the 900 and 1800 MHz bands. We found that the highest exposure level averaged over the cell medium that includes evaluated cells (monolayer or suspension) used in 51 of the 80 studies corresponds to 2 W/kg or less, a level below the limit defined for the general public. That does not take into account any exposure non-uniformity. For comparison, we estimated, by numerical means using dipoles and a commercial mobile phone model, the maximum conservative exposure of superficial tissues from sources operated in the 900 and 1800 MHz bands. The analysis demonstrated that exposure of skin, blood, and muscle tissues may well exceed 40 W/kg at the cell level. Consequently, in vitro studies reporting minimal or no effects in response to maximum exposure of 2 W/kg or less averaged over the cell media, which includes the cells, may be of only limited value for analyzing risk from realistic mobile phone exposure. We, therefore, recommend future in vitro experiments use specific absorption rate levels that reflect maximum exposures and that additional temperature control groups be included to account for sample heating. Bioelectromagnetics © 2015 Wiley Periodicals, Inc.
... Power densities can also be calculated from an antenna provided enough information is given. [7][8][9][10][11][12][13][14][15][16][17][18][19][20], have applied a number of methods to investigate the possible health effects owing to human exposure to EMF radiations from mobile phone base stations. A 2003 survey study carried out by Santini [9] in France found a variety of self-reported symptoms such as fatigue, headache, sleep disruption and loss of memory for people who reported that they were living within 100 m of base stations in urban areas or within 300 m of GSM cell towers in rural areas. ...
Article
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ABSTRACT For some time now, members of the public have been concerned about the possible feared health impacts and safety of new RF technologies, including radar, radio and television broadcasting facilities, microwave ovens, pointto-point microwave radio, and satellite communications systems. The most recent concern is the safety of mobile phones and their base stations (BSs). In Nigerian some people believed that exposure to radiation from BSs for long period could cause different diseases like cancer, destroys reproductive organs, congenital anomalies, epilepsy and persistent headache and some of the BSs were installed near the home of residence. Owing to the growing concern, this study was conducted to evaluate the radio frequency radiation levels near several mobile phone BSs in GRA, Benin City, Nigeria. Measurements in terms of power density were made to check the exposure level at public locations. The data (power density) were collected from three (3) major GSMoperators BSs in Nigeria; all the BSs were located in GRA, Benin City, Nigeria. For each of these BSs the measurements were taken at 5m intervals to 100m from the BSs. From the results, the maximum of power density obtained for GLo, MTN and Airtel are 1.62mW/m2, 3.04mW/m2 and 1.52mW/m2 respectively. These values are quite small compared to international standard limits like those adopted by the International Commission on Non-ionizing Radiation Protection (ICNIRP) which is 9mW/m2 for the public and 22.5mW/m2 for those professionals involved in telecommunication industry. Keywords: Radio Frequency Electromagnetic Radiation, Base Station Antenna, Power density, international Commission on non-ionizing radiation protection.
... Показано, что непосредственными проявлениями электромаг нитного воздействия могут быть нарушение сна, снижение памяти и познавательной функции, утомляемость, раздражительность, депрессии, нарушения гематоэнцефалического барьера и ба ланса нейротрансмиттеров, цитологические из менения в нервных клетках мозга и разрывы ни тей ДНК, а в качестве последствий -нейродеге неративные заболевания и развитие опухолей мозга. [1, [9][10][11][12]. ...
Article
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The research deals with the effect of low-intensity 900 MHz frequency electromagnetic radiation (EMR), power density 25 μW/cm2, on the following rat brain and blood serum enzyme activities: creatine kinase (CK), playing a central role in the process of storing and distributing the cell energy, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) that play a key role in providing the conjunction of carbohydrate and amino acid metabolism. The comparative analysis of the changes in the enzyme activity studied at different times following the two-hour single, as well as fractional, radiation equivalent of the total time showed that the most radiosensitive enzyme is the brain creatine kinase, which may then be recommended as a marker of the radio frequency radiation impact. According to the analysis of the changing dynamics of the CK, ALT and AST activity level, with time these changes acquire the adaptive character and are directed to compensate the damaged cell energy metabolism.
... Однако эти результаты не удалось повторить в экспериментах Gruenau et al. [387]. Напротив, в исследованиях Schirmacher et al. [678] in vitro при воздействии ЭМП РЧ 1,8 ГГц выявлено изменение проницаемости гематоэнцефалического барьера для сахарозы. Shivers с соавторами [689], Prato et al. [624] удалось выявить повышение проницаемости гематоэнцефалического барьера для альбумина при комбинированном воздействии ЭМП РЧ и импульсного или статического магнитного поля. ...
Book
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The book presents and summarizes the results of experimental studies on the reaction of biological systems subcellular, cellular, system, and organism levels in response to nonionizing electromagnetic radiofrequency fields, factors associated with the explosion of wires in condensed matter, magnetic and electric fields.
... Only one available in vitro study analyzed the effect of MW in the BBB model system. 48 This model was a coculture of rat astrocytes and porcine brain capillary endothelial cells (BCEC). Samples were characterized morphologically by scanning electron microscopy and immunocytochemistry. ...
Chapter
Both potentially detrimental and beneficial responses of living cells to weak, nonthermal (NT) electromagnetic fields (EMF) have been observed. So far, focus has been on biological effects of extremely low frequency (ELF, 1–300 Hz) EMF and EMF of microwave frequency range (MW, 300 MHz to 300 GHz). There is strong evidence that biological effects of EMF are dependent on many physical, physiological, and genetic parameters, which must be controlled in replication studies. 1,2 Source of funding may also affect the data. 3 While a significant body of published data shows biological effects of NT MW, studies supported by the mobile industry are less likely to report these effects. 3,4 Failure to control important parameters in replicated studies along with reduced funding for EMF research in economically developed countries may be the main cause of the lack of accepted mechanism for biological effects of NT EMF. While funding for mechanistic EMF studies has been significantly reduced, the number of sources for ELF and MW exposure in everyday life is constantly growing. Moreover, some modern devices emit EMF in wide frequency ranges covering both ELF and MW. In particular, mobile phones not only expose the user to MW but also to ELF. 5–10 ITIS Foundation has performed detailed measurement of five mobile phones. 11 All five phones have shown the maximum B-field on the back side with extrapolated pulse heights between 35 and 75 μT. At this location, four out of the five tested phones exceeded the International Commission on Non-Ionizing Radiation Protection (ICNIRP) reference levels by several harmonics of 217 Hz. The maximum violation by a factor of two was detected at 650 Hz. The B-field on the front side of the phones tested is by a factor two to six times smaller and varies between eight and 20 μT. The maximum DC fields were detected near the phone loudspeaker and reached levels up to 20 mT (half of the corresponding ICNIRP reference level of 40 mT). Perentos et al. have recently measured and characterized the ELF magnetic field from several GSM handsets using different probes which covered frequency range from static magnetic fields (0 Hz) to 2 GHz. Peak ELF fields at the front sides of five commercial GSM phones were assessed and a maximum of 22.4 μT was reported. 12 The main ELF component at 217 Hz was about 1 μT at a distance of 3 cm from the front side of the handset. The overall pulse peak was 4.2 times greater than the 217 Hz component. The 217 Hz magnetic field decreased with distance and reached 0.3 μT at approximately 5 cm from the front handset site. The overall ELF pulse peak produced by all ELF components was 4.2 times greater than the 217 Hz component.
... The fact that results have been contradictory is not unexpected since there were large methodological differences between the studies. This being so, some studies have shown increased permeability Fritze et al., 1997;Neubauer et al., 1990;Nittby et al., 2009;Salford et al., 1994Salford et al., , 2003Schirmacher et al., 2000;Tang et al., 2015;Töre et al., 2001) whereas others reported no effect (de Gannes et al., 2009;Finnie et al., 2009Finnie et al., , 2002Finnie et al., , 2001Franke et al., 2005a,b;Grafstrom et al., 2008;Kuribayashi et al., 2005;Masuda et al., 2007a,b;Tsurita et al., 2000). The matter is complicated further by the lack of a general mechanism by which mobile phone radiation at non-thermal exposure levels might adversely affect BBB function, though alterations of physicochemical characteristics of membranes for example have been suggested (Pall, 2013;Shivers et al., 1987). ...
Article
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For some time it has been investigated whether low-intensity non-thermal microwave radiation from mobile phones adversely affects the mammalian blood-brain barrier (BBB). All such studies except one have been either in vitro or experimental animal studies. The one carried out on humans showed a statistically significant increase in serum transthyretin (TTR) 60min after finishing of a 30-min microwave exposure session. The aim of the present study was to follow up on the finding of the previous one using a better study design. Using biomarkers analyzed in blood serum before and after the exposure this single blinded randomized counterbalanced study, including 24 healthy subjects aged 18-30 years that all underwent three exposure conditions (SAR10G=2W/kg, SAR10G=0.2W/kg, sham), tested whether microwaves from an 890-MHz phone-like signal give acute effects on the integrity of brain-shielding barriers. Over time, statistically significant variations were found for two of the three biomarkers (TTR; β-trace protein); however, no such difference was found between the different exposure conditions nor was there any interaction between exposure condition and time of blood sampling. In conclusion this study failed to show any acute clinically or statistically significant effect of short term microwave exposure on the serum levels of S100β, TTR and β-trace protein with a follow up limited to two hours. The study was hampered by the fact that all study persons were regular wireless phone users and thus not naïve as to microwave exposure. Copyright © 2015. Published by Elsevier Ireland Ltd.
... Because permeability change of BBB has been a matter of concern as it could result in health hazard on the brain, many research groups attempted to confirm their results. However, a few studies (Schirmacher et al., 2000;Aubineau and Tore, 2005) found in the low-level RF-EMF affect BBB permeability in vivo and in vitro, whereas others (Tsurita et al., 2000;Franke et al., 2005a,b;Kuribayashi et al., 2005;Finnie et al., 2006) failed to replicate Salford's findings (Salford et al., 1994(Salford et al., , 2003. ...
... Oscar and Hawkins early performed studies on effects of radio frequency (RF) uponthe brain when they demonstrated that at very low energy levels (< 10W/m 2 ), the fields in a restricted exposure window caused a significant leakage of 14 Cmannitol, innulin and also dextran (same molecular weight as albumin) from the capillariesinto the surrounding cerebellar brain tissue (Oscar and Hawkins1977). Nonetheless, recent studies have also shown that Electromagnetic frequency at 1.8 GHz increases the permeability to sucrose of the brain (Schirmacher et al. 2000). Other Studies inferred that this part of the central nervous system in exposure to RF, pulsed and static magnetic fields usually give rise to a significant pinocytotic transport of albumin from the capillaries into the brain. ...
Article
Full-text available
This review study discusses the public perspectives based on cell phones radiation exposure to particularly the human brain, concentrating on the behavioral effect and disease factors due to RF exposures. Health endpoints reported to be associated with RF which includes brain tumors, genotoxic effects, neurological effects, immune system deregulation, allergic responses and some cardiovascular effects are classified and reviewed. This review however showed that there is strong and robust evidence that chronic exposures to electro magnetic frequency or radio frequency or microwave fields across the spectrum, through strength, consistency, biological plausibility and many dose-response relationships, cause increased rates of brain cancer and other carcinogenic symptoms. It can therefore be related that there is no safe threshold because of the genotoxic nature of the mechanism that may however be involved. The discussed study explains that the cell phone induced effects upon the blood –brain barrier permeability and in continuous hours of exposure to RF radiation may result in significant increase in protein extravasations. Animal species of the sub group reviewed in this study are characterized by symptoms such as a decreased loco motor activity, increased grooming and reduced memory functions due to continuous long hour's exposure to RF-EMR at specified absorption rate during their early days of infancy.
... e triplica la permeabilità a quattro giorni (P = .001) alle radiazioni dei cellulari GSM 1800 MHz (Schirmacher et al., 2000). ...
Book
Full-text available
Il problema dell’invasività e dei rischi dei campi elettromagnetici ad alta frequenza è già stato trattato dalle nostre Associazioni. Nel corso degli anni si sono accumulate numerose evidenze sull’effetto nefasto di questa forma di inquinamento sulla salute umana e sull’ambiente. Nell’ultimo decennio sono state diffuse risoluzioni scientifiche e governative, consensi scientifici e documenti di posizione, rapporti di gruppi di scienziati indipendenti e appelli ai governi per invitare a limitare la diffusione dell’uso di tecnologie di comunicazione promuovendo standard di sicurezza per i campi elettromagnetici basati su evidenze biologiche. Alle raccomandazioni provenienti dal mondo scientifico, purtroppo, come nel caso dei pesticidi, delle emissioni in atmosfera e degli inquinanti organici persistenti (POP), è generalmente seguita una notevole inerzia normativa sia a livello europeo che nazionale. Ancora di più è trascurato, a livello politico e amministrativo, l’effetto sinergico di queste fonti di inquinamento, così come il Principio di Precauzione che dovrebbe guidare qualsiasi scelta in ambito gestionale. Nel frattempo i campi elettromagnetici artificiali e l’inquinamento diffuso hanno continuato ad aumentare significativamente per motivazioni più legate a interessi economici privati che a effettive necessità o al concreto interesse per la salute pubblica e la tutela ambientale. Negli ultimi tempi una notevole inquietudine si è diffusa anche presso i non addetti ai lavori per la nuova tecnologia 5G che minaccia, in un quadro già pericoloso almeno a livello locale, un ulteriore incremento dei campi elettromagnetici artificiali e l’utilizzo di frequenze mai utilizzate su così ampia scala in assenza di regole adeguate e di efficaci sistemi di monitoraggio dell’esposizione pubblica. Per questi motivi e per porre, ancora una volta, all’attenzione pubblica e ai mass media i rischi correlati a queste tecnologie abbiamo trattato in maniera per quanto possibile sintetica le informazioni provenienti dalla ricerca scientifica, offrendo al lettore una notevole bibliografia con la quale aumentare la propria conoscenza e farsi una propria idea della situazione presente, a nostro parere già inquietante. Le conclusioni a cui siamo giunti è che, se è vero che non si possono bloccare le innovazioni tecnologiche, esse devono essere tuttavia impiegate su larga scala solo dopo averne compiutamente considerato i possibili impatti ambientali e sanitari e solo dopo un efficace adeguamento delle normative in relazione alle conoscenze scientifiche, privilegiando la salute e l’ambiente prima di qualsiasi interesse economico. Per tutelare la salute pubblica si rende indispensabile recepire gli studi scientifici più recenti ed attuare quanto indicato dalla Raccomandazione 1815 dell’Assemblea Plenaria del Consiglio d’Europa del 2011, volta ad abbassare i limiti di esposizione alle radiofrequenza in relazione all’uso privato di telefoni mobili, telefoni DECT (cordless), WiFi, WLAN e WIMAX per computer, Baby Phones a 0,2 V/m sul “lungo termine”, mentre secondo il rapporto Bionitiative 2012 sulla base delle evidenze sperimentali e del principio di precauzione deve essere portato a 0,6 V/m nell’immediato. In relazione al 5G, fermi restando i presupposti di cui sopra, è necessaria una moratoria per valutare adeguatamente gli effetti sulla salute e sull’ambiente delle frequenze utilizzate, anche in relazione alla loro prevista onni-pervadenza. Vanno inoltre valutati i possibili effetti sulla sempre più folta comunità degli Elettrosensibili e sui soggetti potenzialmente più vulnerabili, come i bambini. Riteniamo inoltre doveroso, sulla base delle evidenze disponibili, il divieto di installazione di reti Wi-Fi negli asili e nelle scuole frequentate da bambini e ragazzi al di sotto dei 16 anni e il divieto di posizionamento di ripetitori di radiotelefonia in prossimità degli stessi luoghi.. Vi deve essere obbligo, per le Agenzie di Salute Pubblica, di valutare i rischi per la salute connessi alle radiofrequenze, selezionando studi scientifici indipendenti ed escludendo quelli finanziati dall’industria delle telecomunicazioni o da fondazioni ed enti finanziati dalla stessa. Riteniamo che debba essere sottoposto a Valutazione Ambientale Strategica l’intera Strategia per le Telecomunicazioni. Ricordiamo che il processo di VAS impone criteri ampi di partecipazione, tutela degli interessi legittimi e trasparenza del processo decisionale, attraverso il coinvolgimento e la consultazione dei soggetti competenti in materia ambientale e del pubblico che in interessato dall’iter decisionale. Auspichiamo la promozione di investimenti pubblici e detassazione per la connettività in fibra ottica e via cavo, che è la tecnologia più efficiente e sicura per la salute e per l’ambiente. Su questi presupposti siamo lieti di offrire al pubblico il nostro rapporto, svolto in modo del tutto indipendente. Gradiamo costruttivi feedback per migliorare ulteriormente la conoscenza di base e la divulgazione delle problematiche correlate all’incremento dei campi elettromagnetici artificiali e alla necessità di un adeguata normativa e di processi per quanto possibile trasparenti e partecipati di valutazione degli impatti delle nuove tecnologie.
... e triplica la permeabilità a quattro giorni (P = .001) alle radiazioni dei cellulari GSM 1800 MHz (Schirmacher et al., 2000). ...
Book
Full-text available
Il problema dell’invasività e dei rischi dei campi elettromagnetici ad alta frequenza è già stato trattato dalle nostre Associazioni. Nel corso degli anni si sono accumulate numerose evidenze sull’effetto nefasto di questa forma di inquinamento sulla salute umana e sull’ambiente. Nell’ultimo decennio sono state diffuse risoluzioni scientifiche e governative, consensi scientifici e documenti di posizione, rapporti di gruppi di scienziati indipendenti e appelli ai governi per invitare a limitare la diffusione dell’uso di tecnologie di comunicazione promuovendo standard di sicurezza per i campi elettromagnetici basati su evidenze biologiche. Alle raccomandazioni provenienti dal mondo scientifico, purtroppo, come nel caso dei pesticidi, delle emissioni in atmosfera e degli inquinanti organici persistenti (POP), è generalmente seguita una notevole inerzia normativa sia a livello europeo che nazionale. Ancora di più è trascurato, a livello politico e amministrativo, l’effetto sinergico di queste fonti di inquinamento, così come il Principio di Precauzione che dovrebbe guidare qualsiasi scelta in ambito gestionale. Nel frattempo i campi elettromagnetici artificiali e l’inquinamento diffuso hanno continuato ad aumentare significativamente per motivazioni più legate a interessi economici privati che a effettive necessità o al concreto interesse per la salute pubblica e la tutela ambientale. Negli ultimi tempi una notevole inquietudine si è diffusa anche presso i non addetti ai lavori per la nuova tecnologia 5G che minaccia, in un quadro già pericoloso almeno a livello locale, un ulteriore incremento dei campi elettromagnetici artificiali e l’utilizzo di frequenze mai utilizzate su così ampia scala in assenza di regole adeguate e di efficaci sistemi di monitoraggio dell’esposizione pubblica. Per questi motivi e per porre, ancora una volta, all’attenzione pubblica e ai mass media i rischi correlati a queste tecnologie abbiamo trattato in maniera per quanto possibile sintetica le informazioni provenienti dalla ricerca scientifica, offrendo al lettore una notevole bibliografia con la quale aumentare la propria conoscenza e farsi una propria idea della situazione presente, a nostro parere già inquietante. Le conclusioni a cui siamo giunti è che, se è vero che non si possono bloccare le innovazioni tecnologiche, esse devono essere tuttavia impiegate su larga scala solo dopo averne compiutamente considerato i possibili impatti ambientali e sanitari e solo dopo un efficace adeguamento delle normative in relazione alle conoscenze scientifiche, privilegiando la salute e l’ambiente prima di qualsiasi interesse economico. Per tutelare la salute pubblica si rende indispensabile recepire gli studi scientifici più recenti ed attuare quanto indicato dalla Raccomandazione 1815 dell’Assemblea Plenaria del Consiglio d’Europa del 2011, volta ad abbassare i limiti di esposizione alle radiofrequenza in relazione all’uso privato di telefoni mobili, telefoni DECT (cordless), WiFi, WLAN e WIMAX per computer, Baby Phones a 0,2 V/m sul “lungo termine”, mentre secondo il rapporto Bionitiative 2012 sulla base delle evidenze sperimentali e del principio di precauzione deve essere portato a 0,6 V/m nell’immediato. In relazione al 5G, fermi restando i presupposti di cui sopra, è necessaria una moratoria per valutare adeguatamente gli effetti sulla salute e sull’ambiente delle frequenze utilizzate, anche in relazione alla loro prevista onni-pervadenza. Vanno inoltre valutati i possibili effetti sulla sempre più folta comunità degli Elettrosensibili e sui soggetti potenzialmente più vulnerabili, come i bambini. Riteniamo inoltre doveroso, sulla base delle evidenze disponibili, il divieto di installazione di reti Wi-Fi negli asili e nelle scuole frequentate da bambini e ragazzi al di sotto dei 16 anni e il divieto di posizionamento di ripetitori di radiotelefonia in prossimità degli stessi luoghi.. Vi deve essere obbligo, per le Agenzie di Salute Pubblica, di valutare i rischi per la salute connessi alle radiofrequenze, selezionando studi scientifici indipendenti ed escludendo quelli finanziati dall’industria delle telecomunicazioni o da fondazioni ed enti finanziati dalla stessa. Riteniamo che debba essere sottoposto a Valutazione Ambientale Strategica l’intera Strategia per le Telecomunicazioni. Ricordiamo che il processo di VAS impone criteri ampi di partecipazione, tutela degli interessi legittimi e trasparenza del processo decisionale, attraverso il coinvolgimento e la consultazione dei soggetti competenti in materia ambientale e del pubblico che in interessato dall’iter decisionale. Auspichiamo la promozione di investimenti pubblici e detassazione per la connettività in fibra ottica e via cavo, che è la tecnologia più efficiente e sicura per la salute e per l’ambiente. Su questi presupposti siamo lieti di offrire al pubblico il nostro rapporto, svolto in modo del tutto indipendente. Gradiamo costruttivi feedback per migliorare ulteriormente la conoscenza di base e la divulgazione delle problematiche correlate all’incremento dei campi elettromagnetici artificiali e alla necessità di un adeguata normativa e di processi per quanto possibile trasparenti e partecipati di valutazione degli impatti delle nuove tecnologie.
... Aggravations of the blood-brain barrier penetrability were reviewed by surveying the extravasation of external tracers or of inside serum constituents. Most scientists agree that steady and beat microwave presentation grows blood-mind block in vitro (Schirmacher et al., 2000) and in vivo (Albert & Kerns, 1981;Frey et al., 1975;Merritt et al., 1978;Oscar & Hawkins, 1977;Sutton & Carrol, 1979), yet a few researchers are at fluctuation to these revelations, in every occasion on condition that restriction allied compression reactions were avoided (Preston et al., 1979). ...
Chapter
Full-text available
With the expanding use of wireless cellular networks, concerns have been communicated about the possible interaction of electromagnetic radiation with the human life, explicitly, the mind and brain. Mobile phones emanate radio frequency waves, a type of non-ionizing radiation, which can be absorbed by tissues nearest to where the telephone is kept. The effects on neuronal electrical activity, energy metabolism, genomic responses, neurotransmitter balance, blood–brain barrier permeability, mental psychological aptitude, sleep, and diverse cerebrum conditions including brain tumors are assessed. Health dangers may likewise develop from use of cellular communication, for instance, car accidents while utilizing the device while driving. These indirect well-being impacts surpass the immediate common troubles and should be looked into in more detail later on. In this chapter, we outline the possible biological impacts of EMF introduction on human brain.
... Exposure to EMW significantly increased permeability for 14C-sucrose compared to unexposed samples. [8] Similarly, the in vitro study of Zhou et al. showed increased BBB permeability after exposure to 100 kV/m and 400 kV/m electromagnetic pulse. [9] Other studies reported the same findings. ...
Purpose: The aim of this study is to investigate the effects of electromagnetic waves (EMWs) emitted by a mobile phone on the intraocular pressure (IOP) in the eyeball. Methods: This quasi-experimental study was conducted on 166 eyes from 83 individuals in the 40-70 age range who referred to "Khatam-al-Anbia Hospital, Mashhad, Iran" in 2016. There were two groups of participants, and the first one consisted of 41 participants who had normal eyes, whereas the second one comprised 42 participants who suffered from open-angle glaucoma disease. The IOP in both groups was measured and recorded by a specialist before and after talking 5 min on the cellphone with the help of the Goldman method. Statistical analysis such as paired t-test and analysis of variance was performed and all tests are statistically significant at (P < 0.05). For this purpose, the SPSS software (version 16) was applied. Results: IOP in the glaucoma eye (42 eyes) ipsilateral to mobile phone before and after the intervention was 18.64 ± 6.7 and 23.53 ± 6.3, respectively (P < 0.001). However, IOP in the control group (41 eyes) ipsilateral to mobile phone before and after the intervention was 12.95 ± 3.5 and 13.39 ± 2.8, respectively (P = 0.063). IOP change in the opposite glaucomatous eye to mobile phone in glaucoma group (39 eyes) and normal group (44 eyes) was not significantly different before and after the phone call (P = 0.065 and P = 0.85, respectively). Conclusion: We found that the acute effects of EMWs emitted from the mobile phones can significantly increase the IOP in glaucoma eye, while such changes were not observed in normal eyes.
... Production of free radicals by NIR is not the only mechanism with scientific support. Production of heat shock proteins indicating physiological stress; altered calcium flux and intracellular calcium signaling; induced ornithine decarboxylase activity; increased permeability of the blood brain barrier; reduced oncostatic effect of melatonin; single and double strand DNA breaks; as well as other mechanisms have been documented (Byrus et al., 1987;Liburdy et al., 1993;Mullins et al., 1999;Schirmacher et al., 2000;Blackman et al., 2001;Leszczynski, 2002;Lai and Singh, 2005;Blank and Goodman, 2009;Pall, 2015;Salford et al., 1994Salford et al., , 2003. ...
Article
Full-text available
This paper attempts to resolve the debate about whether non-ionizing radiation (NIR) can cause cancer–a debate that has been ongoing for decades. The rationale, put forward mostly by physicists and accepted by many health agencies, is that, “since NIR does not have enough energy to dislodge electrons, it is unable to cause cancer.” This argument is based on a flawed assumption and uses the model of ionizing radiation (IR) to explain NIR, which is inappropriate. Evidence of free-radical damage has been repeatedly documented among humans, animals, plants and microorganisms for both extremely low frequency (ELF) electromagnetic fields (EMF) and for radio frequency (RF) radiation, neither of which is ionizing. While IR directly damages DNA, NIR interferes with the oxidative repair mechanisms resulting in oxidative stress, damage to cellular components including DNA, and damage to cellular processes leading to cancer. Furthermore, free-radical damage explains the increased cancer risks associated with mobile phone use, occupational exposure to NIR (ELF EMF and RFR), and residential exposure to power lines and RF transmitters including mobile phones, cell phone base stations, broadcast antennas, and radar installations.
... There are 2 main categories of EMFs: extremely low frequency (ELF) and radiofrequency (RF) waves. 13) ELFs can be generated from electrical lines or transmission towers, issues of which have been investigated for the last several decades. RFs can be generated from mobile phones and smart devices and the recent 5thgeneration (5G) technologies. ...
Article
Full-text available
In today's world, most children are exposed to various manmade electromagnetic fields (EMFs). EMFs are electromagnetic waves less than 300 GHz. A developing child's brain is vulnerable to electromagnetic radiation; thus, their caregivers' concerns about the health effects of EMFs are increasing. EMF exposure is divided into two categories: extremely low frequencies (ELFs; 3-3,000 Hz), involving high-voltage transmission lines and in-house wiring; and radio frequencies (RFs; 30 kHz to 300 GHz), involving mobile phones, smart devices, base stations, WiFi, and 5G technologies. The biological effects of EMFs on humans include stimulation, thermal, and nonthermal, the latter of which is the least known. Among the various health issues related to EMFs, the most important issue is human carcinogenicity. According to the International Agency for Research on Cancer's (IARC's) evaluation of carcinogenic risks to humans, ELFs and RFs were evaluated as possible human carcinogens (Group 2B). However, the World Health Organization's (WHO's) view of EMFs remains undetermined. This article reviews the current knowledge of EMF exposure on humans, specifically children. EMF exposure sources, biological effects, current WHO and IARC opinions on carcinogenicity, and effects of EMF exposures on children will be discussed. As well-controlled EMF experiments in children are nearly impossible, scientific knowledge should be interpreted objectively. Precautionary approaches are recommended for children until the potential health effects of EMF are confirmed.
... EMF has been reported to increase the permeability of the bloodbrain barrier, while this increase in permeability causes changes in the central nervous system by giving rise to physical changes (Schumacher et al., 2000;Salford et al., 1994;Nittby et al., 2009). A large number of studies have also shown the effect of EMF applied in the pre-and postnatal periods on central nervous system tissues. ...
Article
The purpose of this study was to investigate hippocampus morphology and changes in learning behavior in male rats in late adolescence exposed to the effect of a continuous 1-h a day 900-megahertz (MHz) electromagnetic field (EMF). Twenty-four male Sprague Dawley rats aged 3-weeks were divided equally into control, sham and EMF groups. EMF group rats were exposed to a 900-MHz EMF inside an EMF cage, while the sham group rats were placed in the same cage but were not exposed to such an effect. No procedure was performed on the control group. Following 25-day application of EMF, passive avoidance, 8-arm radial maze and Y-maze tests were applied to determine rats' learning and memory performances. Open field and rotarod tests were applied to assess locomotor activity. At the end of the tests, the animals' brains were removed. Sections were taken and stained with toluidine blue. The regions of the hippocampus were subjected to histopathological evaluation. At histopathological examination, impairments of pyramidal and granular cell structures were observed in the EMF group hippocampus. No significant change was observed in learning, memory or locomotor behavior in any group. In conclusion, 900-MHz EMF applied in early and mid-adolescence causes no changes in learning, memory or locomotor behavior.
... Numerous bioelectromagnetic studies were based on these close waveguides even though they are not suitable for real-time observation. For example, rectangular waveguides were used to investigate the effects of GSM signals on the permeability of cells [87] and other biological effects [88]. Besides, the temperature within a close waveguide cannot be controlled and the structure does not allow air flow. ...
Thesis
The evolution and increasing use of mobile communications systems was associated with laboratory investigations to study radiofrequency electromagnetic waves exposure safety. In this context, this thesis focuses on the characterization of exposure systems allowinglaboratory in vitro studies on cell models. A dual numerical and experimental approach is implemented to perform the devices dosimetry allowing to determine and control the exposure levels. One of the limitations associated with this dosimetry is due to the micrometric dimensions involved. Therefore, a microscopy technique based on a temperature-dependent fluorescent dye named Rhodamine B was set up and evaluated. This assessment recommends an optimal concentration of the dye at around 50 μM. After calibration, it is possible to estimate the specific absorption rate (SAR) from the temperature variation, even for low levels of SAR (< W / kg) with a spatial resolution of less than ten micrometers i.e. microdosimetry. The two main exposure systems studied, based on microelectrode arrays (MEA), allow the recording of neurons electrophysiological activity. Exposure to electromagnetic waves is achieved simultaneously by inserting these MEAs into TEM cells exposure systems. Dosimetry carried out at 1.8 GHz shows a higher sensitivity of one MEA to its environment. It was shown that the modifications made to the second MEA such as its aperture size and ground planes, have reduced the proximity environment influence. The microdosimetry demonstrated good homogeneity of the SAR between the electrodes with an estimated value of 7 ± 1 W / kgfor 1 W incident power. Finally, a microfluidic exposure device based on a coplanar waveguide was characterized under static conditions.
... An increase in its normally low permeability for hydrophilic and charged molecules could potentially be detrimental [26]. " EMR causes increased BBB permeability [27][28][29][30][31][32][33][34]. BBB increased permeability decreases cerebral blood flow and conversely one may confer that increased cerebrovascular blood flow indicates a decrease to BBB permeability [35,36]. ...
Article
Full-text available
Citation: Smirnov IV (2018) The Effect of the Mret Wave Rider Device on Cerebral Blood Flow and the Blood Brain Barrier: A Case Study. J Nanotech Smart Mater 3: 1-8. Abstract Biological effects of electromagnetic fields (EMF) on the blood-brain barrier (BBB) and cerebral blood flow can be studied using optical encephalography. Previous investigations of the permeability of the blood-brain barrier after exposure to the various EMF-components showed an induced leakage of Evans Blue labeled proteins normally not passing the BBB. In the present investigation we exposed a human subject to ambient radiation and the flow of the blood at the frontal part of the brain was measured using16-channel optical encephalography. The Optical Encephalograph is a functional Near-Infrared Spectroscopy (fNIRS) device that monitors PO2 and Hemoglobin (Hb) levels and translates the data into an indication of blood flow. The MRET WaveRider® noise field generator which is capable of decreasing BBB permeability by neutralizing EMR was turned onand the flow of the blood at the frontal part of the brain was measured using 16-channel optical encepha-lography. The MRET polymer compound is driven by the solenoid that encapsulates the polymer material (WaveRider®). The composite noise field can modify RF signals as a result of superposition phenomenon. When the WaveRider®noise field was in effect, the cerebral blood flow (increased PO2 and Hb) increased from 337.209 seconds to 864.419 seconds at the termination of the testing, indicating that these measurements were previous to the Wave Rider initiation affects.
... However, the effect of non-thermal RF-EMF exposure on blood-brain barrier is still unclear. Some studies suggest that mobile phone radiation, at non-thermal exposure levels, increases permeability of bloodbrain barrier in vivo (Salford et al., 1994) and in vitro (Schirmacher et al., 2000), whereas others report the lack of such effects (Fritze et al., 1997a;Tsurita et al., 2000). However, the no-effect claimed by Fritze et al. (1997a) is not so straight forward as suggested by the authors because they reported induction of stress response and increased permeability of the blood-brain barrier immediately after irradiation. ...
Book
Full-text available
Today‘s world is very much polluted and very much risky for the living beings. There are many factors which are inhibiting our growth and increasing various diseases in human population and in other animals also. So I have summarized these factors in this book. This book has mainly focused on effects of mobile phone radiation on living beings. It dealt with various pathways in a cell undergoing changed due to radiations. I have tried to update as much information as I could in all the chapters. I have searched many articles and research work done till now to collect the latest information for the readers. I shall greatly appreciate interaction with the readers and shall welcome any suggestions/criticisms from the students as these would surely help me to improve the work. This book also contains a project study which demonstrates that how radiation can affect cell physiology and can produce tumors. It is expected that this book will surely provide a idea about the relation of radiation and their harmful effects. Thus it will make the people aware about their health. This is the main purpose of this book. I shall in any case welcome any suggestions/criticism for further improvement, since there surely remains a limitless scope for the same.
... However, the effect of non-thermal RF-EMF exposure on blood-brain barrier is still unclear. Some studies suggest that mobile phone radiation, at non-thermal exposure levels, increases permeability of bloodbrain barrier in vivo (Salford et al., 1994) and in vitro (Schirmacher et al., 2000), whereas others report the lack of such effects (Fritze et al., 1997a;Tsurita et al., 2000). However, the no-effect claimed by Fritze et al. (1997a) is not so straight forward as suggested by the authors because they reported induction of stress response and increased permeability of the blood-brain barrier immediately after irradiation. ...
Book
Full-text available
... It impedes the infl ux of toxic molecules from blood into the brain. However, this impairment is controversial (20,21). Higher permeability of BBB renders some substances, toxins and harmful material to leak out of the bloodstream into the brain cells and tissues. ...
... Many approaches has been applied in previous research studies (e.g. [5][6], [7][8][9][10][11][12][13][14][15][16][17][18][19][20]), to investigate the possible health effects owing to human exposure to EMF radiations from mobile phone BSs. In 2003, survey approach via the use of questionnaires was applied in [9] to investigate the possible health hazard impact on people residing near cellular phone BSs in France. ...
Article
Full-text available
This study is designed to appraise the level of radio frequency electromagnetic field (RF-EMF) radiation emanating from GSM base stations (BSs) in Ikoyi, Lagos State, Nigeria. Extensive EMF strength measurements were carried out on randomly selected BSs in the study locations, and a detailed analysis of this location set was performed. The measurements for the field strength were taken in seven selected locations with special focus on busy streets, squares and other public places. The information from each location, where a measurement was performed (about 770 readings in totality), was displayed as per attached histogram charts with fitted Gaussian curves, where the exposure levels were compared to those of International Commission for Non Ionize Radiation Protection (ICNIRP). The field strength data obtained was found to be between a minimum value of (3.09E-05V/m) and a maximum of (1.23E-02V/m), which is quite small compared to the standard of International Commission for Non Ionize Radiation Protection (ICNIRP) limits. The results also showed a large spatial variation in field strength data values. The variations may be attributed to moving objects (e.g cars, persons), density of mobile phones users, differences in radio engineering/environmental parameters, e.g. input power of the base station (BS), type height and spatial distribution of buildings in the investigated region.
Article
The societal need for new central nervous system (CNS) medicines is substantial, because of the global increase in life expectancy and the accompanying increase in age-related CNS diseases. Low blood–brain barrier (BBB) permeability has been one of the major causes of failure for new CNS drug candidates. There has therefore been a great interest in cell models, which mimic BBB permeation properties. In this review, we present an overview of the performance of monocultured, cocultured, and triple-cultured primary cells and immortalized cell lines, including key parameters such as transendothelial electrical resistance values, permeabilities of paracellular flux markers, and expression of BBB-specific marker proteins. Microfluidic systems are gaining ground as a new automated technical platform for cell culture and systematic analysis. The performance of these systems was compared with current state-of-the-art models and it was noted that, although they show great promise, these systems have not yet reached beyond the proof-of-concept stage. In general, it was found that there were large variations in experimental protocols, BBB phenotype markers, and paracellular flux markers used. It is the author's opinion that the field may benefit greatly from developing standardized methodologies and initiating collaborative efforts on optimizing culture protocols.
Technical Report
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The Radiofrequency Toolkit was developed in response to requests from BC’s medical and environmental health officers to the BCCDC for assistance in assessing and communicating the risk to health from exposure to the many devices which emit radiofrequency waves. Students, public health residents, and specialists in epidemiology from outside BCCDC collaborated with staff from BCCDC and the National Collaborating Center for Environmental Health (NCCEH) on this project. The toolkit provides background on the physics of RF, its sources, measurement and exposure characteristics as well as an evaluation of the current scientific literature on potential biological and health effects associated with exposure to RF.
Article
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These days' mobile phones becoming an elementary part of our life. This is one of the most important medium for the communication. The countless increase in mobile phones has increased the amount of non-ionizing radio waves in surroundings during last two decades the possible risks by radio frequency electromagnetic field exposure of the human body are a major concern for the society. Although the familiarization and dependency of mobile phone is growing at an alarming pace, the Human health effects due to the exposure of radiations have become a subject of intense debate. The effects of radio-frequency radiation is very broad and heterogeneous. the possibility of a relationship between mobile phone use and carcinogenic processes, reproduction and development, the cardiovascular system and longevity – that is, exposure of the whole body. The rate at which radiation is absorbed by the human body is measured by the Specific Absorption Rate (SAR), and its maximum levels for modern handsets have been set by governmental regulating agencies in many countries.
Article
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This study designed to detect pathological effects of exposure to 2.45 MHz radiofrequency electromagnetic field with low power densities on mature male albino rats. 36 rats at 3-4 months age were used in the study, randomly devided to 6 groups with 6 animals for each group. The groups from 1-5 were exposed to 2.45 MHz radiofrequency electromagnetic field with different power densities : ( 5 MW/cm2 , 1 MW/cm2 , 500 µW/cm2 , 50 µW/cm2 and 10 µW/cm2, respectively). The 6th group represented non exposed control group. The exposed groups received 6 hours of exposure daily for 21 days as an exposure period. Clinical signs were observed daily and body weight and rectal temperature were monitored weekly. At the end of exposure period 3 animals were killed from each group for gross and histopathological examination , the other 3 animals were left for another 21 days without exposure represented post exposure period to detect the ability of rats to recover from the induced pathological changes if existed. The results showed occurrence of clinical signs at all exposed groups and more severe at group 1 manifested by nervous excitation at 1st hour of exposure followed by depression and stagnation to the end of 6 hours of exposure. There was no significant difference between the groups in body weight averages at the 3 weeks of experiment. A significant decrease in post exposure rectal temperature comparing with pre exposure rectal temperature has been noticed at groups 1 and 2 in 1st week and at group 3 in 2nd week of experiment with no significant differences in other groups. Gross and histopathological examination at the end of exposure period revealed presence of some pathological changes at group 1 manifested by perineuronal edema, mild microglial proliferation and congestion in the brain, in lungs there was acute bronchopneumonia with pulmonary vascular arteriosclerosis, there was also mucinous degeneration in duodenal epithelium with congestion of small intestine, in kidneys there was acute cell swelling of renal tubular epithelium with congestion. These changes less severely occurred at the groups 2 and 3, the exposed groups 4 and 5 similar to control did not show any pathological changes. At the end of post exposure period, pathological changes were detected at the groups 1,2 and 3 represented by bronchopneumonia and mucinous degeneration of small intestine .These changes were lighter than those observed at the end of exposure period .
Chapter
The blood-brain and spinal cord barriers strictly regulate the microfluid environment of the central nervous system (CNS). A slight alteration in the CNS microfluid environment results in abnormal neuronal function. Several short- or long-term stressful conditions are associated with immediate early gene expression, alterations in neurochemical transmission, and impairment of the microvascular barrier permeability. A possibility exists that stress-induced breakdown of the microvascular barriers is one of the most important events leading to neurodegeneration. Based on our investigations and in the light of recent knowledge, the functional significance of microvascular permeability disturbances in stressful situations in relation to brain damage is discussed.
Thesis
The aim of this work was to simulate human exposure to high power pulsed microwave (HPM) emitted by radars of the French Navy. Navy staff exposure to radars may be occasional, prolonged or repeated depending on activities aboard. It was necessary to investigate their potential health effects in order to contribute to the risk assessment and anticipate potential litigation. A special emitting experimental device was developed in order to reproduce different exposure conditions at 3 GHz with an experimental model of adult rat. We present here the in vivo results obtained after 3 GHz exposure under non thermal conditions - acute (DAS 5 W/kg), chronic (DAS 15 W/kg) and chronic associated with repeated acute exposure (mixed) –for short, middle and long term effects on adult rat. The dosimetry was obtained by numerical simulation (FDTD) and completed with experimental measurements. Parameters related to the central nervous system, especially on blood brain barrier (BBB) and apoptosis were observed. The effects on cognitive function were assessed by different types of behavioral tests on memory, learning, anxiety, aggressiveness and locomotion of adult rat. Regular body weighing and clinical check-up including tumor incidence with sampling and histological examination were performed on rats. In parallel, hematological parameters were examined with complete blood count and immunological system was studied. The endocrine pathway involved in stress management have been studied through adrenocorticotrope hormone (ACTH) and corticosterone assays. No significant behavioral effect either on memory, learning, anxiety, aggressiveness, overall neurological evaluation either or on locomotion of adult rat. Results did not show any effect on central nervous system in our experimental conditions. No significant effect was observed on weight gain of rats after non thermal microwave exposure. Results on hematological parameters, on immunological parameters, on stress hormones and on tumors development did not detected any non thermal effect in our experimental conditions
Article
Since the Royal Society of Canada report on potential health risks or radiofrequency (RF) fields from wireless telecommunications in the spring of 1999, there have been several newly published reports on risks associated with the use of mobile phones. This article provides a summary of scientific research on the potential health effects of radiofrequency fields that has been reported since the original Royal Society report was published. This update also discusses several earlier results not included in the original report.
Article
In this study, the effects of low-level, GSM emitted ElectroMagnetic Field (EMF) on Amyloid Precursor Protein (APP) and alpha-synuclein (α-syn) in human neuroblastoma cells was investigated. Our data indicated alterations on APP processing and cellular topology, following EMF exposure (ℇ = 10.51 V/m, SAR = 0.23 W/kg, exposure time: 3 times, for 10 min, for 2 days). Furthermore, changes in monomeric α-syn accumulation and multimerization, as well as induction of oxidative stress and cell death, were documented. The results presented here require further investigation to determine potential links of EMF with the molecular pathogenic mechanisms in Alzheimer's and Parkinson's Diseases.
Article
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This study designed to detect pathological effects of exposure to 2.45 MHz radiofrequency electromagnetic field with low power densities on mature male albino rats. 36 rats at 3-4 months age were used in the study, randomly devided to 6 groups with 6 animals for each group. The groups from 1-5 were exposed to 2.45 MHz radiofrequency electromagnetic field with different power densities : ( 5 MW/cm2 , 1 MW/cm2 , 500 μW/cm2 , 50 μW/cm2 and 10 μW/cm2, respectively). The 6th group represented non exposed control group. The exposed groups received 6 hours of exposure daily for 21 days as an exposure period. Clinical signs were observed daily and body weight and rectal temperature were monitored weekly. At the end of exposure period 3 animals were killed from each group for gross and histopathological examination , the other 3 animals were left for another 21 days without exposure represented post exposure period to detect the ability of rats to recover from the induced pathological changes if existed. The results showed occurrence of clinical signs at all exposed groups and more severe at group 1 manifested by nervous excitation at 1st hour of exposure followed by depression and stagnation to the end of 6 hours of exposure. There was no significant difference between the groups in body weight averages at the 3 weeks of experiment. A significant decrease in post exposure rectal temperature comparing with pre exposure rectal temperature has been noticed at groups 1 and 2 in 1st week and at group 3 in 2nd week of experiment with no significant differences in other groups. Gross and histopathological examination at the end of exposure period revealed presence of some pathological changes at group 1 manifested by perineuronal edema, mild microglial proliferation and congestion in the brain, in lungs there was acute bronchopneumonia with pulmonary vascular arteriosclerosis, there was also mucinous degeneration in duodenal epithelium with congestion of small intestine, in kidneys there was acute cell swelling of renal tubular epithelium with congestion. These changes less severely occurred at the groups 2 and 3, the exposed groups 4 and 5 similar to control did not show any pathological changes. At the end of post exposure period, pathological changes were detected at the groups 1,2 and 3 represented by bronchopneumonia and mucinous degeneration of small intestine .These changes were lighter than those observed at the end of exposure period .
Article
The biological effects of electromagnetic pulse (EMP) on the brain have been focused on for years. It was reported that gelatinase played an important role in maintaining brain function through regulating permeability in the blood–brain barrier (BBB). To investigate the effects of EMP on gelatinase of BBB, an in vitro BBB model was established using primary cultured rat brain microvascular endothelial cells (BMVEC), astrocytes and half-contact culture of these cells in a transwell chamber. Cultured supernatant and cells were collected at different time points after exposure to EMP (peak intensity 400 kV/m, rise time 10 ns, pulse width 350 ns, 0.5 pps and 200 pulses). Protein levels of cellular gelatinase MMP-2 and MMP-9, and endogenous inhibitor TIMP-1 and TIMP-2 were detected by Western blot. The activity of gelatinase in culture supernatant was detected by gelatin zymography. It was found that compared with the sham-exposed group, the protein level of MMP-2 was significantly increased at 6 h (p < 0.05), and the protein level of its endogenous inhibitor TIMP-2 did not change after EMP exposure. In addition, the protein levels of MMP-9 and its endogenous inhibitor TIMP-1 did not change after EMP exposure. Gelatin zymography results showed that the activity of MMP-2 in the inner pool and the outer pool of the transwell chamber was significantly increased at 6 h after EMP exposure compared with that of the sham group. These results suggested that EMP exposure could affect the expression and activity of MMP-2 in the BBB model.
Article
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Biological effects of radio frequency electromagnetic fields (EMF) on the blood‐brain barrier (BBB) have been studied in Fischer 344 rats of both sexes. The rats were not anaesthetised during the exposure. All animals were sacrificed by perfusion–fixation of the brains under chloralhydrate anaesthesia after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter perfusion fixed with 4% formaldehyde for 5–6 minutes. Whole coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 µm. Albumin and fibrinogen were demonstrated immunohistochemically and classified as normal versus pathological leakage. In the present investigation we exposed male and female Fischer 344 rats in a Transverse Electromagnetic Transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse‐modulated with different pulse power and at various time intervals. The CW‐pulse power varied from 0.001 W to 10 W and the exposure time from 2 min to 960 min. In each experiment we exposed 4–6 rats with 2–4 controls randomly placed in excited and non‐excited TEM‐cells respectively. We have in total investigated 630 exposed rats at various modulation frequencies and 372 controls. The frequency of pathological rats is significantly increased (p p p
Article
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Astrocytes, a member of the glial cell family in the central nervous system, are assumed to play a crucial role in the formation of the blood-brain barrier (BBB) in vertebrates. It was shown that astrocytes induce BBB-properties in brain capillary endothelial cells (BCEC) in vitro. We now established an astroglial cell line of non-tumoral origin. The cloned cell line (A7) shows a highly increased proliferation rate and expresses the astrocytic marker glial fibrillary acidic protein. Furthermore, the clone A7 expresses S-100-protein and vimentin, which are also expressed by primary cultured astrocytes. This cell line therefore shows general astrocytic features. In addition, we were able to show that A7 cells re-induce the BBB-related marker enzyme alkaline phosphatase in BCEC, when these two cell types are co-cultured. Thus we have a cell line which can be readily cultured in large quantities, shows common astrocyte properties and is able to influence BCEC with respect to a BBB-related feature.
Article
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Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.
Article
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Biological effects of electromagnetic fields (EMF) on the blood-brain barrier (BBB) can be studied in sensitive and specific models. In a previous investigation of the permeability of the blood-brain barrier after exposure to the various EMF-components of proton magnetic resonance imaging (MRI), we found that the exposure to MRI induced leakage of Evans Blue labeled proteins normally not passing the BBB of rats [Salford et al. (1992), in: Resonance Phenomena in Biology, Oxford University Press, pp. 87-91]. In the present investigation we exposed male and female Fischer 344 rats in a transverse electromagnetic transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse-modulated with repetition rates of 8, 16, 50, and 200 s-1. The specific energy absorption rate (SAR) varied between 0.016 and 5 W/kg. The rats were not anesthetized during the 2-hour exposure. All animals were sacrificed by perfusion-fixation of the brains under chloral hydrate anesthesia about 1 hour after the exposure. The brains were perfused with saline for 3-4 minutes, and thereafter fixed in 4% formaldehyde for 5-6 minutes. Central coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 microns. Albumin and fibrinogen were demonstrated immunohistochemically. The results show albumin leakage in 5 of 62 of the controls and in 56 of 184 of the animals exposed to 915 MHz microwaves. Continuous wave resulted in 14 positive findings of 35, which differ significantly from the controls (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
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In view of the methodological problems of epidemiological studies on associations between exposures to Hz magnetic fields (MF) and increased incidence of cancers, laboratory studies are necessary to determine if Hz MF are cancer promoters or can progress cancers. The objective of the present study was to determine if an alternating MF of low flux density exerts tumorpromoting or co-promoting effects in a model of breast cancer in female rats. Mammary tumors were induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). A group of 99 rats was exposed to a homogeneous MF of 50 Hz, 100 μT (microtesla), for 24 h/day 7 day/week for a period of 91 days; another group of 99 rats was sham-exposed under the same environmental conditions as the MF-exposed rats. The exposure chambers were identical for MF-exposed and sham-exposed animals. DMBA was administered orally at a dose of 5 mg/kg at the first day of exposure and at weekly intervals thereafter up to a total dose of 20 mg per rat. The animals were palpated once weekly to assess the development of mammary tumors. In controls, DMBA induced tumors in about 40% of the animals within three months of first application. Eight weeks after DMBA application the MF-exposed rats exhibited significantly more tumors than sham-exposed animals. This difference in the rate of tumor development was observed throughout the period of exposure. At the end of the three-month period of MF exposure the tumor incidence in MF-exposed rats was 50% higher than in sham-exposed rats, the difference being statistically significant. Furthermore, the size of tumors as estimated by palpation was significantly larger in the MF-exposed compared to sham-exposed rats. The data demonstrates that long-term exposure of DMBA-treated female rats to an alternating MF of low flux density promotes the growth and increases the incidence of mammary tumors, thus strongly indicating that MF exposure exerts tumor-promoting and/or copromoting effects.
Article
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We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier using a calibrated microwave exposure system in the 900 MHz band. Rats were restrained in a carousel of circularly arranged plastic tubes and sham-exposed or microwave irradiated for a duration of 4 h at specific brain absorption rates (SAR) ranging from 0.3 to 7.5 W/kg. The extravasation of proteins was assessed either at the end of exposure or 7 days later in three to five coronal brain slices by immunohistochemical staining of serum albumin. As a positive control two rats were subjected to cold injury. In the brains of freely moving control rats (n = 20) only one spot of extravasated serum albumin could be detected in one animal. In the sham-exposed control group (n = 20) three animals exhibited a total of 4 extravasations. In animals irradiated for 4 h at SAR of 0.3, 1.5 and 7.5 W/kg (n = 20 in each group) five out of the ten animals of each group killed at the end of the exposure showed 7, 6 and 14 extravasations, respectively. In the ten animals of each group killed 7 days after exposure, the total number of extravasations was 2, 0 and 1, respectively. The increase in serum albumin extravasations after microwave exposure reached significance only in the group exposed to the highest SAR of 7.5 W/kg but not at the lower intensities. Histological injury was not observed in any of the examined brains. Compared to other pathological conditions with increased blood-brain barrier permeability such as cold injury, the here observed serum albumin extravasations are very modest and, moreover, reversible. Microwave exposure in the frequency and intensity range of mobile telephony is unlikely to produce pathologically significant changes of the blood-brain barrier permeability.
Article
The belts of endothelial tight junctions, which impede diffusion between blood and brain, were reduced to fragmentary, small junctions in subcultured brain endothelium. When cocultured with the capillaries' nearest neighbor, the astrocytes, these endothelial tight junctions were enhanced in length, width, and complexity, as seen by en face views of the cell membranes with freeze-fracture electron microscopy. Gap junctions, common in brain endothelium in vitro but absent in mature brain capillaries in vivo, were markedly diminished in area from among the enhanced tight junctions of the cocultures. Thus, astrocytes in vitro play a role in the formation, extent, and configuration of the junctional complexes in brain endothelium, whose diffusion barrier may likewise be influenced by astrocytes in vivo.
Article
Whether radiofrequency (RF) fields are carcinogenic is controversial; epidemiological data have been inconclusive and animal tests limited. The aim of the present study was to determine whether long-term exposure to pulse-modulated RF fields similar to those used in digital mobile telecommunications would increase the incidence of lymphoma in E mu-Pim1 transgenic mice, which are moderately predisposed to develop lymphoma spontaneously. One hundred female E mu-Pim1 mice were sham-exposed and 101 were exposed for two 30-min periods per day for up to 18 months to plane-wave fields of 900 MHz with a pulse repetition frequency of 217 Hz and a pulse width of 0.6 ms. Incident power densities were 2.6-13 W/m2 and specific absorption rates were 0.008-4.2 W/kg, averaging 0.13-1.4 W/kg. Lymphoma risk was found to be significantly higher in the exposed mice than in the controls (OR = 2.4. P = 0.006, 95% CI = 1.3-4.5). Follicular lymphomas were the major contributor to the increased tumor incidence. Thus long-term intermittent exposure to RF fields can enhance the probability that mice carrying a lymphomagenic oncogene will develop lymphomas. We suggest that such genetically cancer-prone mice provide an experimental system for more detailed assessment of dose-response relationships for risk of cancer after RF-field exposure.
Article
The design and selection of centrally acting pharmaceuticals is a major challenge for drug delivery to the brain. This review discusses the use of physicochemical parameters and cell culture models to predict blood-brain barrier permeability. Physicochemical parameters have been successfully used to predict blood-brain barrier penetration of molecules that exhibit passive transport and that do not affect junctional permeability, are not transported by a carrier or receptor and are not subject to metabolism or apical recycling. In vitro cell culture models use the brain microvessel endothelial cells that constitute the blood-brain barrier in vivo. Although these cells undergo some de-differentiation in culture, primary endothelial cultures have been shown to maintain several morphological, biochemical and functional properties of the blood-brain barrier in vivo. Bovine brain microvessel endothelial cell systems have been successfully used to generate in vitro/in vivo correlations. These endothelial cell culture models can also be used to study transport mechanisms. This information can be utilized in the design of compounds that either penetrate into or are excluded from the brain.
Article
The passage of substances across the blood–brain barrier (BBB) is regulated in the cerebral capillaries, which possess certain distinct different morphological and enzymatic properties compared with the capillaries of other organs. Investigations of the functional characteristics of brain capillaries have been facilitated by the use of cultured brain endothelial cells, but in most studies some characteristics of the in vivo BBB are lost. To provide an in vitro system for studying brain capillary functions, we have developed a process of coculture that closely mimics the in vivo situation by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. In order to assess the drug transport across the blood–brain barrier, we compared the extraction ratios in vivo to the permeability of the in vitro model. The in vivo and the in vitro values showed a strong correlation. The relative ease with which such cocultures can be produced in large quantities facilitates the screening of new centrally active drugs. This model provides an easier, reproducible and mass-production method to study the blood–brain barrier in vitro.
Article
The characteristics of the waves guided along a plane [I] P. S. Epstein, “On the possibility of electromagnetic surface waves, ” Proc. Nat’l dcad. Sciences, vol. 40, pp. 1158-1165, Deinterface which separates a semi-infinite region of free cember 1954. space from that of a magnetoionic medium are investi- [2] T. Tamir and A. A. Oliner, “The spectrum of electromagnetic waves guided by a plasma layer, ” Proc. IEEE, vol. 51, pp. 317gated for the case in which the static magnetic field is 332, February 1963. oriented perpendicular to the plane interface. It is [3] &I. A. Gintsburg, “Surface waves on the boundary of a plasma in a magnetic field, ” Rasprost. Radwvoln i Ionosf., Trudy found that surface waves exist only when w,<wp and NIZMIRAN L’SSR, no. 17(27), pp. 208-215, 1960. that also only for angular frequencies which lie bet\\-een [4] S. R. Seshadri and A. Hessel, “Radiation from a source near a plane interface between an isotropic and a gyrotropic dielectric,” we and 1/42 times the upper hybrid resonant frequency. Canad. J. Phys., vol. 42, pp. 2153-2172, November 1964. The surface waves propagate with a phase velocity [5] G. H. Owpang and S. R. Seshadri, “Guided waves propagating along the magnetostatic field at a plane boundary of a semiwhich is always less than the velocity of electromagnetic infinite magnetoionic medium, ” IEEE Trans. on Miomave waves in free space. The attenuation rates normal to the Tbory and Techniques, vol. MTT-14, pp. 136144, March 1966. [6] S. R. Seshadri and T. T. \Vu, “Radiation condition for a maginterface of the surface wave fields in both the media are netoionic medium. ” to be Dublished. examined. Kumerical results of the surface wave characteristics are given for one typical case.
Article
Rats were exposed to 1.3 gHz microwave energy to assess the uptake of several neutral polar substances in certain areas of the brain. A quantitative, radioactive isotope method, which uses an internal standard, was employed to measure the loss of test substances to brain tissue. Single, 20 min exposure, to either pulsed or continuous wave (CW) microwave energy induced an increase in the uptake of D-mannitol at average power densities of less than 3.0 mW/sp. cm. The permeability change was greatest in the medulla, followed, in decreasing order, by the cerebellum and hypothalamus, with small or negligible changes in the hippocampus and cortex. Permeability increases were observed for mannitol and inulin but not for dextran. Increased permeability was observed both immediately and 4 h after exposure, but not 24 h after exposure. After an initial rise, the permeability of cerebral vessels to saccharides decreased with increasing microwave power. Differences in the level of uptake occurred between CW energy and pulsed energy of the same average power. Microwaves of the same average power but different pulse characteristics also produced different uptake levels. Our findings suggest that microwaves induce a temporary change in the permeability for small molecular weight saccharides in the blood-brain barrier system of rats.
Article
It has been shown both in vivo and in culture that astrocytes communicate with brain microvessel endothelial cells (BMECs) to induce many of the blood-brain barrier characteristics attributed to these unique cells. However, the results using cultured cells are conflicting as to whether this communication is dependent upon cell-cell contact. In this study we used primary cultures of bovine BMECs grown as monolayers on polycarbonate filters to study the formation of the barrier in vitro and examine its modulation by rat C6 glioma cells. Effects were examined by treating postconfluent BMEC monolayers with medium conditioned continually by C6 cells from the basolateral side to mimic the in vivo orientation. Cell monolayer integrity was assessed using electrical resistance and by measuring diffusion of uncharged molecules. BMEC monolayers form a functionally polarized and leaky barrier, with maximal resistance of 160 omega . cm2 and significant flux of molecules of molecular weight less than 350 Da. Treatment with rat or human astroglioma cells rather than pericytoma cells or transformed fibroblasts results in a concentration-dependent 200-440% increase in electrical resistance and a coincident 50% decrease in permeability to sucrose and dextran (70 kDa). The decrease in passive diffusion is most likely due to a change in tight junctions and not to transcellular vesicular traffic. The findings support that astroglioma cells release one or more signals that are required for cultured BMECs to express a "differentiated" phenotype associated with a tighter barrier, increased gamma-glutamyl transpeptidase activity, and decreased pinocytic activity. The relative ease and quickness of this culture system makes it amenable to studies on cell-cell interaction and regulation of barrier maintenance.
Article
Radio-frequency electromagnetic radiation (RFR) at 915 and 147 MHz, when sinusoidally amplitude modulated (AM) at 16 Hz, has been shown to enhance release of calcium ions from neuroblastoma cells in culture. The dose-response relation is unusual, consisting of two power-density "windows" in which enhanced efflux occurs, separated by power-density regions in which no effect is observed. To explore the physiological importance of these findings, we have examined the impact of RFR exposure on a membrane-bound enzyme, acetylcholinesterase (AChE), which is intimately involved with the acetylcholine (ACh) neurotransmitter system. Neuroblastoma cells (NG108), exposed for 30 min to 147-MHz radiation, AM at 16 Hz, demonstrated enhanced AChE activity, as assayed by a procedure using 14C-labeled ACh. Enhanced activity was observed within a time window between 7.0 and 7.5 h after the cells were plated and only when the exposure occurred at power densities identified in a previous report as being effective for altering the release of calcium ions. Thus RFR affects both calcium-ion release and AChE activity in nervous system-derived cells in culture in a common dose-dependent manner.
Article
Adult AMES mice and male Sprague Dawley rats were exposed to an artificial magnetic field, generated by Helmholtz coils. 3.5 hours after the onset of darkness the coils were activated for one hour resulting in an inversion of the horizontal component of the earth's magnetic field. The coils were activated and deactivated at 5 min intervals during the 1 hour exposure period. In both mice and rats, the levels of serotonin in the pineal were markedly increased by the exposure. In rats, an increase of pineal 5-hydroxyindole acetic acid and a decrease of the activity of the pineal enzyme serotonin-N-acetyltransferase also was observed. However, pineal and serum melatonin levels were not altered. The results indicate that the metabolism of serotonin in the pineal is quickly affected by the exposure of animals to a magnetic field.
Article
To provide an "in vitro" system for studying brain capillary function, we have developed a process of coculture that closely mimics the "in vivo" situation by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. Under these conditions, endothelial cells retain all the endothelial cell markers and the characteristics of the blood-brain barrier, including tight junctions and gamma-glutamyl transpeptidase activity. The average electric resistance for the monolayers was 661 omega cm2. The system is impermeable to inulin and sucrose but allows the transport of leucine. Arabinose treatment increases transcellular transport flux by 70%. The relative ease with which such monolayers can be produced in large quantities would facilitate the "in vitro" study of brain capillary functions.
Article
The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging- and sex-related alterations in the permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.
Article
The belts of endothelial tight junctions, which impede diffusion between blood and brain, were reduced to fragmentary, small junctions in subcultured brain endothelium. When cocultured with the capillaries' nearest neighbor, the astrocytes, these endothelial tight junctions were enhanced in length, width, and complexity, as seen by en face views of the cell membranes with freeze-fracture electron microscopy. Gap junctions, common in brain endothelium in vitro but absent in mature brain capillaries in vivo, were markedly diminished in area from among the enhanced tight junctions of the cocultures. Thus, astrocytes in vitro play a role in the formation, extent, and configuration of the junctional complexes in brain endothelium, whose diffusion barrier may likewise be influenced by astrocytes in vivo.
Article
A novel method has been developed for the preparation of nearly pure separate cultures of astrocytes and oligodendrocytes. The method is based on (a) the absence of viable neurons in cultures prepared from postnatal rat cerebra, (b) the stratification of astrocytes and oligodendrocytes in culture, and (c) the selective detachment of the overlying oligodendrocytes when exposed to sheer forces generated by shaking the cultures on an orbital shaker for 15--18 h at 37 degrees C. Preparations appear greater than 98% pure and contain approximately 1-2 x 10(7) viable cells (20--40 mg of cell protein). Three methods were used to characterize these two culture t ypes. First, electron microscopic examination was used to identify the cells in each preparation (mixed and separated cultures of astrocytes and oligodendrocytes) and to assess the purity of each preparation. Second, two oligodendroglial cell markers, 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37) and glycerol phosphate dehydrogenase (EC 1.1.1.8) were monitored. Third, the regulation of cyclic AMP accumulation in each culture type was examined. In addition to these studies, we examined the influence of brain extract and dibutyryl cAMP on the gross morphology and ultrastructure of each preparation. These agents induced astroglial process formation without any apparent morphological effect on oligodendrocytes. Collectively, the results indicate that essentially pure cultures of astrocytes and of oligodendrocytes can be prepared and maintained. These preparations should significantly aid in efforts to examine the biochemistry, physiology, and pharmacology of these two major classes of central nervous system cells.
Article
Intravenously injected [14C]sucrose was used as a small molecular weight (342 daltons), hydrophilic tracer for determination of 2450 MHz CW microwave and ambient heat effects on rat blood-brain barrier permeability in the cerebral cortex, hypothalamus, cerebellum and medulla. The tracer was injected 4 min following exposure of conscious, unrestrained rats to microwaves at 0 or 65 mW/cm2 for 30 or 90 min (SAR approximately equal to 13.0 W/kg) or to ambient heat (42 +/- 2 degrees C) for 90 min. Comparison of mean permeability-surface area products (PA) and uptake ratios between sham and microwave-exposed animals revealed a statistically significant (P less than 0.05) decrease of both PA and uptake ratios for the hypothalamus, cerebellum and medulla of rats exposed to microwaves for 30 min. This decrease was not apparent for rats exposed to microwaves for 90 min. A pertinent observation, with regard to this latter group of animals, was the increased circulating levels of the tracer when colonic temperature was raised to approximately 41.4 degrees C or higher.
Article
A National Research Council report concludes that ordinary exposure to electromagnetic fields from power lines and household appliances does not cause cancer, neurobehavioral disorders, or reproductive and developmental problems. But the debate over EMFs is unlikely to be put to rest.
Article
Previous studies found associations between childhood leukemia and surrogate indicators of exposure to magnetic fields (the power-line classification since known as "wire coding"), but not between childhood leukemia and measurements of 60-Hz residential magnetic fields. We enrolled 638 children with acute lymphoblastic leukemia (ALL) who were under 15 years of age and were registered with the Children's Cancer Group and 620 controls in a study of residential exposure to magnetic fields generated by nearby power lines. In the subjects' current and former homes, data collectors measured magnetic fields for 24 hours in the child's bedroom and for 30 seconds in three or four other rooms and outside the front door. A computer algorithm assigned wire-code categories; based on the distance and configuration of nearby power lines, to the subjects' main residences (for 416 case patients and 416 controls) and to those where the family had lived during the mother's pregnancy with the subject (for 230 case patients and 230 controls). The risk of childhood ALL was not linked to summary time-weighted average residential magnetic-field levels, categorized according to a priori criteria. The odds ratio for ALL was 1.24 (95 percent confidence interval, 0.86 to 1.79) at exposures of 0.200 mu T or greater as compared with less than 0.065 mu T. The risk of ALL was not increased among children whose main residences were in the highest wire-code category (odds ratio as compared with the lowest category, 0.88; 95 percent confidence interval, 0.48 to 1.63). Furthermore, the risk was not significantly associated with either residential magnetic-field levels or the wire codes of the homes mothers resided in when pregnant with the subjects. Our results provide little evidence that living in homes characterized by high measured time-weighted average magnetic-field levels or by the highest wire-code category increases the risk of ALL in children.
Article
We have successfully cultured choroid plexus epithelial cells from porcine brain in pure form by the addition of cytosine arabinoside to the culture medium which prevented growth of other contaminating cells. We characterized the cells in culture by the presence of desmoplakin, fibronectin, thrombospondin, and the zonula occludens protein ZO-1 in comparison to frozen fractions of the isolated choroid plexus tissue. The cells in culture express those marker proteins and moreover exhibit a polarized phenotype which was expected from the presence of tight junction strands that correlate to an electrical resistance of 120 Ohm.cm2 measured across the cell monolayer on a permeable support. Permeability studies with fluorescein-labeled dextrans also indicate a biochemical tightness. The polarity of the cells is demonstrated by the presence of microvilli and cilia on the surface of the cultured cells as well as by the laser scanning microscopic determination of the apical localization of the ZO-1-protein and the Na+K(+)-ATPase. Thrombospondin and fibronectin were found to be localized at the basolateral membrane side. The cells in culture secrete medium containing prealbumin predominantly into the apical compartment which demonstrates that they are able to release medium containing CSF-proteins and therefore verifies the usefulness of this in vitro model.
Article
The acute effect of global system for mobile communication (GSM) microwave exposure on the genomic response of the central nervous system was studied in rats by measuring changes in the messenger RNAs of hsp70, the transcription factor genes c-fos and c-jun and the glial structural gene GFAP using in situ hybridization histochemistry. Protein products of transcription factors, stress proteins and marker proteins of astroglial and microglial activation were assessed by immunocytochemistry. Cell proliferation was evaluated by bromodeoxyuridine incorporation. A special GSM radiofrequency test set, connected to a commercial cellular phone operating in the discontinuous transmission mode, was used to simulate GSM exposure. The study was conducted at time averaged and brain averaged specific absorption rates of 0.3 W/kg (GSM exposure), 1.5 W/kg (GSM exposure) and 7.5 W/kg (continuous wave exposure), respectively. Immediately after exposure, in situ hybridization revealed slight induction of hsp70 messenger RNA in the cerebellum and hippocampus after 7.5 W/kg exposure, but not at lower intensities. A slightly increased expression of c-fos messenger RNA was observed in the cerebellum, neocortex and piriform cortex of all groups subjected to immobilization, but no differences were found amongst different exposure conditions. C-jun and GFAP messenger RNAs did not increase in any of the experimental groups. 24 h after exposure, immunocytochemical analysis of FOS and JUN proteins (c-FOS, FOS B, c-JUN JUN B, JUN D), of HSP70 or of KROX-20 and -24 did not reveal any alterations. Seven days after exposure, neither increased cell proliferation nor altered expression of astroglial and microglial marker proteins were observed. In conclusion, acute high intensity microwave exposure of immobilized rats may induce some minor stress response but does not result in lasting adaptive or reactive changes of the brain.
Article
The immortalised RBE4 cell line, derived from rat brain capillary endothelial cells, preserves many features of the in vivo brain endothelium, and hence is of interest as a potential in vitro model of the blood-brain barrier (BBB). This study reports the effects of elevated intracellular cAMP and factors released by astrocytes on the F-actin cytoskeleton and paracellular sucrose permeability of monolayers of RBE4 cells. RBE4 cells grown in control medium showed a marked increase in the F-actin staining at the cytoplasmic margin at confluence, which was not significantly enhanced by elevation of intracellular cAMP and/or addition of astrocyte-conditioned medium (ACM). The formation of the marginal band of F-actin was accompanied by an increase in the F-actin content of the RBE4 cells up to confluence, and a decline in F-actin content thereafter. Elevation of intracellular cAMP or co-culture above astrocytes significantly decreased the paracellular sucrose permeability of confluent RBE4 cell monolayers grown on collagen filters (P < 0.01 and P < 0.001, respectively). Co-culture above astrocytes together with elevated cAMP also produced a significant decrease in the sucrose permeability of the monolayer (P < 0.01) but this was no greater than with astrocytes alone. These findings show that the RBE4 cell line may serve as a useful in vitro model for the study of brain endothelial cell physiology and agents which alter the permeability of the BBB.
Article
Due to the wide and growing use of mobile communication, there is increasing concern about the interactions of electromagnetic radiation with the human organism, and, in particular, with the brain. In the present report, experimental studies on putative electrophysiological, biochemical and morphological effects of continuous or pulsed microwave radiation are briefly reviewed. Such effects have been described in vitro and in vivo using animals and humans. Particularly, effects on neuronal electrical activity, cellular calcium homeostasis, energy metabolism, genomic responses, neurotransmitter balance and blood-brain barrier permeability have been reported. However, some results have either been disputed, since experimental replication led to contradictory findings, or been related to procedural side effects. Since neurological disturbances induced by mobile telephone devices would be of considerable interest for public health, the authors recognize that further experimental studies, involving strict positive and negative control conditions, will be required in the future. At the present state of knowledge there is no positive evidence that pulsed or continuous microwave exposure in the non-thermal range confers elevated risk to the health of the brain.
Article
The present paper scrutinizes the application of impedance spectroscopy and quartz-crystal microbalance (QCM) measurements in the analysis of composite layers of receptor containing lipid bilayers, and their interaction with external ligands or pore-forming peptides. The formation of supramolecular structures and their analysis will be discussed. Impedance measurement allows one to follow the adsorption of proteins on artificial membranes. This method is even more suitable for quantifying changes in membrane conductivity induced by channel peptides incorporated into the lipid membrane. The QCM is another sophisticated method for analyzing ganglioside-lectin and ganglioside-toxin interactions. A critical comparison between both methods will be given. Moreover, we will demonstrate that the QCM method, especially in combination with impedance analysis, is a completely new approach for determining electrical and viscoelastic properties of epithelial and endothelial cell monolayers that form controlled barriers in vivo.
Article
With the increasing use of cellular telephones, the potential influences of radio-frequency electromagnetic fields (EMF) on human well-being are a focus of public interest. Seven healthy men and three women volunteers aged between 26 and 36 years underwent a single-blind placebo-controlled protocol to investigate the influence of the EMF of a mobile telephone (GSM 900 MHz, 2 Watt, 217 Hz frame repetition rate) on blood pressure (BP), heart rate (HR), capillary perfusion (CP), and subjective well-being. The telephone was fixed in a typical position on the right-hand side of the head and operated by remote control, so that the volunteer did not know whether or not the phone emitted EMF. BP and HR were measured continuously with a Finapres device and CP with an infrared plethysmograph on the right hand. The protocol was divided into phases with placebo and with EMF exposure of 35 min each. A fixed sequence was chosen instead of a randomised order,
Article
The increasing number of newly developed drugs demands for functional in vitro models of the blood-brain barrier to determine their brain uptake. Cultured cerebral capillary endothelial cells are considered to be such a model, however in serum containing media they exhibit low electrical resistances and high permeabilities compared to the in vivo situation. Here we report the establishment of a serum-free cell culture model. Withdrawal of serum already caused a twofold increase of transendothelial resistance (TER), which in presence of serum is about 100-150 Omega x cm2. We tested several supplements and found that hydrocortisone is a potent stimulator for the formation of barrier properties. TERs up to 1000 Omega x cm2 were measured in the presence of physiological relevant hydrocortisone concentrations. In correspondence to the TER increase hydrocortisone decreased cell monolayer permeability for sucrose down to 5x10(-7) cm/s, which is close to the in vivo value of 1.2x10(-7) cm/s and by a factor of five lower compared to cultures without hydrocortisone and in presence of serum.
Article
Primary cultures of porcine brain capillary endothelial cells grown on collagen coated polycarbonate membranes were used to build up an in vitro-model for the blood-brain barrier. Improved cultivation techniques allowed cell-storage and experiments under serum-free conditions. We employed this model to perform permeability studies in vitro with the radioactively labelled marker substances sucrose, retinoic acid, retinol, haloperidol, caffeine, and mannitol. Permeability values obtained with this blood-brain barrier model (1. 0x10-6 cm/s for sucrose, 6.2x10-6 cm/s for retinoic acid, 4.8x10-6 cm/s for retinol, 49.5x10-6 cm/s for haloperidol, 62.4x10-6 cm/s for caffeine, and 1.8x10-6 cm/s for mannitol) show a good correlation to data which are already known from in vivo-experiments. As judged by the sucrose permeability our blood-brain barrier model is less permeable than numerous other models published so far. Therefore it represents a powerful tool for in vitro-prediction of blood-brain barrier permeability of drugs and offers the possibility to scan a large quantity of drugs for their potential to enter the brain.
Article
Due to the high permeability of endothelial cell layers derived from macrovascular vessels, precise determination of their barrier function towards ion movement requires refined experimental techniques. We thus cultured bovine aortic endothelial cells (BAEC) directly on thin gold-film electrodes and measured the electrochemical impedance to study their passive electrical properties in general and during beta-adrenergic stimulation. Impedance spectra (10-2.10(6) Hz) of confluent cell monolayers revealed that the electrical characteristics of the cells can be modelled by a simple resistor-capacitor parallel network. Under control conditions the overall resistance of confluent BAEC monolayers was 3.6+/-0.6 Omega.cm2 (n=30) and the capacitance was 0. 6+/-0.1 microF/cm2. Both quantities are discussed with respect to morphological characteristics of these cells. Stimulation of BAECs with the synthetic beta-adrenoceptor agonist isoproterenol leads to a concentration-dependent, highly specific increase of the cell layer resistance characterized by a concentration for half-maximal response (EC50) of 0.3+/-0.1 microM. The cell layer capacitance, however, remained unaffected. Using impedance measurements at a single frequency, we analysed the response of BAECs to treatment with isoproterenol in comparison with several chemically unrelated compounds known to stimulate the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent signal transduction cascade. These studies confirmed that the enhancement of the cell layer resistance after beta-adrenergic stimulation is mediated by an increase in intracellular cAMP.
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