| 1. |
- Persson, Bertil R.R., et al.
(författare)
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A Model for Evaluating Therapeutic Response of Combined Cancer Treatment Modalities : Applied to Treatment of Subcutaneously Implanted Brain Tumors (N32 and N29) in Fischer Rats with Pulsed Electric Fields (PEF) and 60Co-gamma Radiation (RT)
- 2003
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Ingår i: Technology in Cancer Research and Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 2:5, s. 459-470
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t1/e = 1 ms were first applied to the tumors. Then within 5 min radiation therapy with 60Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively, Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV 0 · exp[TGR · t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogene-therapy.
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| 2. |
- Persson, Bertil R.R., et al.
(författare)
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Radioecological modelling of Polonium-210 and Caesium-137 in lichen-reindeer-man and top predators
- 2018
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Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 186, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- This work deals with analysis and modelling of the radionuclides 210Pb and210Po in the food-chain lichen-reindeer-man in addition to 210Po and 137Cs in top predators. By using the methods of Partial Least Square Regression (PLSR) the atmospheric deposition of 210Pb and 210Po is predicted at the sample locations. Dynamic modelling of the activity concentration with differential equations is fitted to the sample data. Reindeer lichen consumption, gastrointestinal absorption, organ distribution and elimination is derived from information in the literature. Dynamic modelling of transfer of 210Pb and 210Po to reindeer meat, liver and bone from lichen consumption, fitted well with data from Sweden and Finland from 1966 to 1971. The activity concentration of 210Pb in the skeleton in man is modelled by using the results of studying the kinetics of lead in skeleton and blood in lead-workers after end of occupational exposure. The result of modelling 210Pb and 210Po activity in skeleton matched well with concentrations of 210Pb and 210Po in teeth from reindeer-breeders and autopsy bone samples in Finland.The results of 210Po and 137Cs in different tissues of wolf, wolverine and lynx previously published, are analysed with multivariate data processing methods such as Principal Component Analysis PCA, and modelled with the method of Projection to Latent Structures, PLS, or Partial Least Square Regression PLSR.
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| 3. |
- Nittby, Henrietta, et al.
(författare)
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Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation
- 2008
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Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462 .- 1521-186X. ; 29:3, s. 219-232
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Tidskriftsartikel (refereegranskat)abstract
- Considering the frequent use of mobile phones, we have directed attention to possible implications on cognitive functions. In this study we investigated in a rat model the long-term effects of protracted exposure to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed for 2 h each week for 55 weeks to radio-frequency electromagnetic radiation at different SAR levels (0.6 and 60 mW/kg at the initiation of the experimental period) emitted by a (GSM-900) test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After this protracted exposure, GSM-900 exposed rats were compared to sham exposed controls. Effects on exploratory behaviour were evaluated in the open-field test, in which no difference was seen. Effects on cognitive functions were evaluated in the episodic-like memory test. In our study, GSM exposed rats had impaired memory for objects and their temporal order of presentation, compared to sham exposed controls (P = 0.02). Detecting the place in which an object was presented was not affected by GSM exposure. Our results suggest significantly reduced memory functions in rats after GSM microwave exposure (P = 0.02).
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| 4. |
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| 5. |
- Salford, Leif, et al.
(författare)
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The mammalian brain in the electromagnetic fields designed by man with special reference to blood-brain barrier function, neuronal damage and possible physical mechanisms
- 2008
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Ingår i: PROGRESS OF THEORETICAL PHYSICS SUPPLEMENT. - 0375-9687. ; :173, s. 283-309
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Konferensbidrag (refereegranskat)abstract
- Life oil earth was formed during billions of years, exposed to, and shaped by the original physical forces such as gravitation, cosmic irradiation, atmospheric electric fields and the terrestrial magnetism. The Schumann resonances at 7.4 Hz are all example of oscillations possibly important for life.(1)) The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity, in the early 20th century long-wave radio and in the 1940-ies short-wave radio. High frequency RF was introduced in the 50-ies as FM and television and during the very last decades, microwaves of the modern communication society spread around the world. Today, however, one third of the world's population is owner of the microwave-producing mobile phones and an even larger number is exposed to the cordless RF emitting systems. To what; extent are all living organisms affected by these, almost everywhere present radio frequency fields? And what will be the effects of many years of continuing exposure? Since 1989 Our group has studied the effects upon the mammalian blood-brain barrier (BBB) in rats by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been shown to cause significantly increased leak-age of the rats' own blood albumin through the BBB of exposed rats, at energy levels of 1W/kg and below, as compared to non-exposed animals in a total series of about two thousand animals.(2)-6)) One remarkable observation is the fact that the lowest energy levels, with whole-body average power densities below 10mW/kg, give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz, at non-thermal SAB-values of 0.2, 2 and 200 mW/kg, gives rise to significant neuronal damage, seen not only 50 days after the exposure 7) but also after 28 days but not after 14 days. Albumin extravasations and uptake into neurons was enhanced after 14 clays, but not after 28.(8)) in our continued research, also the non-thermal effects oil tissue structure and memory function of long-term exposure for 13 months are studied.(9)) We have also performed microarray analysis of brains from rats exposed to short term GSM both at 1,800 MHz and at 900MHz and have found significant effects upon gene expression of membrane associated genes as compared to control animals.(10),11)) Most of our findings support that living organisms are affected by the non-thermal radio frequency fields. Some other Studies agree while others find no effects. The mechanisms by which the EMFs may alter BBB permeability are not Well Understood. At low field strengths, the effects on body temperature are negligible and thus heating effects are not involved. A change in the physicochemical characteristics of membranes has been suggested as a cause.(12)) We have performed experiments to verify a quantum mechanical model for interaction with protein-bound ions. Our results show that controlled frequency and amplitude of ELF EM fields upon spinach plasma vesicles can steer transport over the membrane.(13)) This may be a first proof of a resonance phenomenon where appropriate levels of frequency and amplitude in the right combination have the potency to communicate with the biology of membranes and transport systems. Our study has prompted Lis to elaborate on magnetic resonance models; the Ion Cyclotron Resonance (ICR) model and the Ion Parametric Resonance (IPR) Model in an attempt to explain the occurrence of resonance frequencies. This is extensively described here under the heading: Mechanisms behind the effects of electromagnetical fields upon biology. We also bring forward the concept of solitons being active in membranes and DNA/RNA-transcription as a, possible mean to understand and prove the biological effects of EMF. The Nishinomiya-Yukawa International and Interdisciplinary Symposium 2007 raised the question: What is Life? An obvious and simple answer could be: It is DNA! The DNA strand can be looked upon as an antenna resonating in the microwave band 6GHz with its harmonics and subharmonics.(14)-18)) If this holds true, the dramatic situation might exist, that all living organisms have a receptor for the newly constructed and world-wide man-made microvaves, leading to a direct effect upon the function of DNA - in concordance with our experimental findings! Our generation invented the microwave emitters. We now have in imperative obligation to further investigate the links between EMF and biology in order to prevent possible detrimental effects of the microwaves.
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| 6. |
- Darte, Lennart, et al.
(författare)
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Quality control of 99mTc-radiopharmaceuticals - Evaluation of GCS minicolumns in routine clinical work with scintillation cameras
- 1980
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Ingår i: European Journal Of Nuclear Medicine. - 0340-6997. ; 5:6, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- Gel chromatography column scanning (GCS) is a rapid and reliable method for the quality control of 99mTc-radiopharmaceuticals. With this method the labelled compound and various impurities such as free pertechnetate, hydrolyzed reduced technetium or other 99mTc-complexes are obtained in one testing procedure. Using minicolumns results can be obtained with a simple testing procedure within a few minutes after the sample is taken; this is significant in routine radiopharmaceutical work. The resolution of the recording system is important, so as to be able to utilize fully the good separation ability of the minicolumn. Minicolumns were studied with some commonly used radiopharmaceuticals. A scintillation camera was used to record minicolumn data under various conditions and the results were compared to those obtained using a scanner to reveal optimal recording conditions for the scintillation camera.
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| 7. |
- Möller, Páll H., et al.
(författare)
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Interstitial laser thermotherapy : Comparison between bare fibre and sapphire probe
- 1995
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Ingår i: Lasers in Medical Science. - 0268-8921. ; 10:3, s. 193-200
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Tidskriftsartikel (refereegranskat)abstract
- A sapphire probe and a bare fibre were compared with respect to temperature control and distribution and light fluence in interstitial laser thermotherapy. Experiments were performed in processed liver using an Nd-YAG laser and output power levels of 1-4 W. The temperature was controlled at a distance of 10 mm using a feedback circuit with an automatic thermometry system and thermistor probes. With the sapphire probe, carbonization was rare at power levels of 1-2 W but was observed in half of the experiments at 3 W and in all experiments at 4 W. Using the bare fibre, carbonization was seen in almost all experiments. Absence of carbonization was associated with a moderate decrease in the penetration of light and excellent control of the temperature, whereas carbonization led to rapid impairment of light penetration and temperature control. In addition, the temperature gradient was smaller with the sapphire probe than with the bare fibre or when carbonization was absent. It is concluded that a diffuser tip, such as the sapphire probe, may be preferable to the bare fibre for interstitial laser thermotherapy because it gives a smaller temperature gradient and helps to avoid carbonization which results in preserved light penetration and improved temperature control.
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| 8. |
- Baureus Koch, Catrin, et al.
(författare)
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Interaction between weak low frequency magnetic fields and cell membranes.
- 2003
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Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462. ; 24:6, s. 395-402
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Tidskriftsartikel (refereegranskat)abstract
- The question of whether very weak low frequency magnetic fields can affect biological systems, has attracted attention by many research groups for quite some time. Still, today, the theoretical possibility of such an interaction is often questioned and the site of interaction in the cell is unknown. In the present study, the influence of extremely low frequency (ELF) magnetic fields on the transport of Ca2+ was studied in a biological system consisting of highly purified plasma membrane vesicles. We tested two quantum mechanical theoretical models that assume that biologically active ions can be bound to a channel protein and influence the opening state of the channel. Vesicles were exposed for 30 min at 32 °C and the calcium efflux was studied using radioactive 45Ca as a tracer. Static magnetic fields ranging from 27 to 37 T and time varying magnetic fields with frequencies between 7 and 72 Hz and amplitudes between 13 and 114 T (peak) were used. We show that suitable combinations of static and time varying magnetic fields directly interact with the Ca2+ channel protein in the cell membrane, and we could quantitatively confirm the model proposed by Blanchard. Bioelectromagnetics 24:395-402, 2003. © 2003 Wiley-Liss, Inc.
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| 9. |
- Belyaev, IY, et al.
(författare)
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Exposure of rat brain to 915 MHz GSM microwaves induces changes in gene expression but not double stranded DNA breaks or effects on chromatin conformation
- 2006
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Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462 .- 1521-186X. ; 27:4, s. 295-306
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether exposure of rat brain to microwaves (MWs) of global system for mobile communication (GSM) induces DNA breaks, changes in chromatin conformation and in gene expression. An exposure installation was used based on a test mobile phone employing a GSM signal at 915 MHz, all standard modulations included, output power level in pulses 2 W, specific absorption rate (SAR) 0.4 mW/g. Rats were exposed or sham exposed to MWs during 2 h. After exposure, cell suspensions were prepared from brain samples, as well as from spleen and thymus. For analysis of gene expression patterns, total RNA was extracted from cerebellum. Changes in chromatin conformation, which are indicative of stress response and genotoxic effects, were measured by the method of anomalous viscosity time dependencies (AVTD). DNA double strand breaks (DSBs) were analyzed by pulsed-field gel electrophoresis (PFGE). Effects of MW exposure were observed on neither conformation of chromatin nor DNA DSBs. Gene expression profiles were obtained by Affymetrix U34 GeneChips representing 8800 rat genes and analyzed with the Affymetrix Microarray Suite (MAS) 5.0 software. In cerebellum from all exposed animals, I I genes were upregulated in a range of 1.34-2.74 fold and one gene was downregulated 0.48-fold (P <.0025). The induced genes encode proteins with diverse functions including neurotransmitter regulation, blood-brain barrier (BBB), and melatonin production. The data shows that GSM MWs at 915 MHz did not induce PFGE-detectable DNA double stranded breaks or changes in chromatin conformation, but affected expression of genes in rat brain cells. Bioelectromagnetics 27:295-306, 2006. (c) 2006 Wiley-Liss, Inc.
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| 10. |
- Capala, J, et al.
(författare)
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Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
- 2003
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Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
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Tidskriftsartikel (refereegranskat)abstract
- A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
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